Evaluation Of Treatment Response Research Articles

Relevant markers for overactive bladder laser therapy: nitric oxide and urinary nerve growth factor.

To investigate the potential of nitric oxide (NO) and urinary nerve growth factor (NGF) as indicators of therapeutic outcomes in overactive bladder (OAB) patients undergoing low-level laser therapy (LLLT) via a prospective randomized controlled trial. Fifty OAB patients participated in the study and were subjected to LLLT using 650-nm laser irradiation. The study employed a prospective randomized controlled trial design. Nitric oxide and urine NGF levels were assessed before and after the LLLT intervention to evaluate their correlation with therapeutic outcomes. The study provided evidence supporting the effectiveness of LLLT as a treatment modality for OAB. Analysis of NO and urine NGF levels revealed significant changes following LLLT intervention suggesting their potential as biomarkers for assessing therapeutic response in OAB patients. These biomarkers hold promise for aiding clinicians in evaluating treatment response and personalizing therapy approaches for OAB patients. This study highlights the utility of LLLT in managing OAB and underscores the importance of exploring biomarkers such as nitric oxide and urinary nerve growth factor to enhance treatment efficacy assessment. The findings suggest that NO and urine NGF levels may serve as valuable indicators of therapeutic outcomes in OAB patients undergoing LLLT. Further research is warranted to elucidate the underlying mechanisms and optimize the clinical application of LLLT in OAB management.

A Cross-Sectional Survey on the Management of Medication Adherence Among Healthcare Professionals in Saudi Arabia

Background/Objectives: Medication adherence is essential for effective healthcare, significantly influencing treatment success and overall health outcomes. However, there is limited understanding of how healthcare professionals in Saudi Arabia manage and support medication adherence. This study aims to examine physicians’ and pharmacists’ approaches to managing medication adherence in Saudi Arabia by examining the methods used for adherence assessment, interventions to enhance adherence, and the challenges faced. Methods: A cross-sectional study was conducted over nine months using a self-administered online questionnaire. The study targeted physicians and pharmacists actively working in Saudi Arabia. The questionnaire was distributed through professional networks to ensure a broad and representative sample. Results: A total of 397 healthcare professionals met the inclusion criteria, comprising 81.1% pharmacists and 18.9% physicians. Direct patient inquiry was the most common assessment method, frequently or always used by 81.3% of physicians and 57.1% of pharmacists. Treatment response evaluation was similarly frequent (89.3% of physicians and 56.2% of pharmacists). Standardized tools, such as the Morisky Medication Adherence Scale, were underutilized (14.7%). Adherence-enhancing interventions focused on patient education, and their use was reported by 89.3% of physicians and 74.2% of pharmacists as frequent or always. Written information was more commonly used by pharmacists (65.8%) than physicians (45.3%). Barriers included excessive workloads and short consultation times (59.9%), absence of effective systems for tracking adherence (51.9%), lack of reliable tools for assessing adherence (48.9%), and insufficient training in behavioral interventions (48.1%). Conclusions: This study reveals significant differences in medication adherence management practices between physicians and pharmacists in Saudi Arabia, emphasizing their distinct roles. Key barriers, including excessive workload, limited consultation time, and inadequate tracking systems, hinder the adoption of evidence-based tools. Tailored interventions, enhanced interprofessional collaboration, and systemic support are essential to address these challenges and improve adherence management, ultimately enhancing patient outcomes.

The current status of tumor markers as biomarkers in the era of immunotherapy for hepatocellular carcinoma: alpha-fetoprotein alone is not sufficient.

Rapid development of systemic treatments has resulted in improved prognosis for unresectable hepatocellular carcinoma (uHCC) patients. Since immune therapy shows a favorable therapeutic efficacy, use of tumor markers as biomarkers for monitoring treatment response is necessary. This study aimed to elucidate changes in positive rates of 3 available tumor markers in Japan, including alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), and lens culinaris agglutinin-reactive AFP (AFP-L3) in uHCC patients treated with systemic therapies over time. From 2009 to 2023, 1470 uHCC patients with data of tumor markers before starting treatment were enrolled. The positivity cut-off value for AFP was 20 ng/mL, for AFP-L3 was 10%, and for DCP was 40 mAU/mL. After dividing the 15 years examined into three periods of five years each (period I, II, III), clinical features of the enrolled patients were evaluated, retrospectively. The percentage of Barcelona Clinic Liver Cancer stage B patients who received systemic therapy increased from period I to III (27.7%, 38.5%, 46.6%, respectively, P<0.001), which was also seen for HCC patients with a non-viral etiology (alcohol and others) (29.9%, 39.7%, 49.6%, respectively P<0.001). Positive rates for AFP (67.8%, 62.1%, 50.8%, respectively) and DCP (84.1%, 80.5%, 72.7%, respectively) were decreased (each P<0.001), while the AFP-L3 rate did not show a significant change (54.4%, 57.7%, 51.9%, respectively P=0.390). Among the AFP-negative patients, the rate of positive for DCP or AFP-L3 was increased (24.4%, 28.1%, 35.4%, respectively, P=0.002). Based on introduction of systemic treatment in an early stage and increasing numbers of HCC cases with a non-viral etiology, the positive rate of AFP level has been declining. Thus, determination of DCP and AFP-L3 in addition to AFP as markers should be more actively utilized in clinical practice, as well as clinical trials for monitoring and evaluating treatment response in this era of combination immunotherapy as a powerful treatment.

Analysis of lumbar dorsal spinal potentials evoked by electrical stimulation of the colon and their changes induced by high-frequency stimulation or ischemia in rats

The clinical-related input and processing of intestinal afferents to the spinal cord is not well known. This study aims to develop an electrophysiological experimental animal model to study spinal cord afferents from the colon during clinical-related conditions such as hyperexcitability or ischemia. Spinal cord evoked potentials (SCEP) were elicited by colonic stimulation in ten male adult Sprague-Dawley rats anesthetized with thiobarbital, 60 mg kg-1 i.p. After laminectomy (T11 to L5), a tungsten electrode (500 μm; &lt;50Ω) was placed in the spinal dorsum to record SCEP induced by bipolar electrical stimulation of colon mucosa (basal 30 V; 1 ms) at low (0.2 Hz; 10 min) or high (5 Hz; 5 min) frequency. In 3 experiments, after the basal recording, a respiratory arrest was induced by D-tubocurarine to evaluate the ischemia effects. The SCEPs were stable and reliable (n=310), displaying a N1 wave (delay: 3.9±0.1 ms; amplitude 7.78±0.39 μV) and P1 wave (delay 9.96±0.14 ms; amplitude 2.97±0.21 μV). Colonic high-frequency stimulation induced an amplitude increase in both +11% (N1) and +23.7% (P1) (p&lt;0.001). The ischemia induced a linear decay of both wave amplitudes more intense for the P1 wave. sensitive. These results denote the intense colonic input to the lumbar dorsal spinal cord, the presence of spinal sensory potentiation mechanisms induced by colonic high frequency stimulation, and the high oxygen dependency of the neuronal networks involved in the N1 and P1 wave generation. This experimental model could contribute to the study of visceral pain and inflammation, allowing the electrophysiological evaluation of experimental treatment response in experimental colon disease models.

Role of cfDNA and DNA integrity index (DII) in colon cancer in response to surgery.

236 Background: Colorectal cancer diagnosis requires new biomarkers for improved detection and monitoring. cfDNA has shown potential in detecting minimal residual disease, evaluating treatment response, and providing prognostic information. Recent studies highlight cfDNA as a promising molecular marker for early disease detection and progression monitoring. This study aims to evaluate the role of cfDNA and DII in assessing surgical response in CRC patients. The primary objective is to assess cfDNA levels pre- and post-curative resection. Secondary objectives include identifying factors influencing baseline cfDNA levels, evaluating factors affecting DII, and comparing cfDNA and CEA levels in response to surgery. Statistical analyses included descriptive statistics, ROC curve, Student T tests and Fisher's exact test. Methods: The study was designed as a prospective investigation conducted over a period from September 2022 to April 2024 at the Regional Cancer Centre. Forty pathologically proven non metastatic colonic carcinoma planned for primary surgery were included and patients with sepsis and chronic diseases were excluded from the study. Blood samples (10 ml) were collected pre-surgery and at four weeks post-surgery. Plasma cfDNA was extracted, quantified, and analyzed via quantitative real-time PCR using human β-actin as a reference. The DII was calculated as the ratio of 394 bp to 99 bp amplicons of β-actin. Results: The mean age was 62.15 years (range 39-85), with 55% over 60 years. High-risk features included poor differentiation (4.2%), preoperative CEA &gt;5 ng/ml (17.5%), LVI (20.8%), and PNI (6.3%). Surgical approaches included 10 laparoscopic, 29 open, and 1 converted from laparoscopic to open due to excessive bleeding. Overall stage grouping showed 18 patients in Stage III, and 11 each in Stage I and II. Median pre- and postoperative cfDNA levels were 24.2 ng/μl and 29.6 ng/μl (p=0.83), and median DNA integrity index levels were 1.1 and 1.0 (p=0.95). Preoperative cfDNA levels averaged 24.2 ng/μl and postoperative levels 29.6 ng/μl (p = 0.83); DII levels were 1.1 preoperatively and 1.0 postoperatively (p = 0.95). Postoperative cfDNA levels decreased in 21 patients and increased in 19, while DII decreased in 20 and increased in 20. Significant associations were noted for cfDNA changes with surgery type and high-risk features. ROC analysis revealed cfDNA cut-off at 275 ng/μl, DII at 1.5, and CEA at 4 µg/L. Sensitivities for cfDNA and DII were 66.67% and 100%, respectively, with combined sensitivity reaching 100%. Conclusions: Persistent high cfDNA levels post-surgery suggest potential minimal residual disease despite radical resection. The residual disease is a harbinger of systemic failure. Monitoring cfDNA and DII can identify patients at risk for recurrence, guiding intensified adjuvant therapy. Further studies with extended follow-up are recommended to validate these findings. Clinical trial information: CTRI/2023/10/058468 .

Short interval circulating tumor DNA (ctDNA) kinetics as a predictor of tumor response in patients with gastrointestinal (GI) cancer receiving immune checkpoint inhibitor (ICI)-based treatment.

836 Background: Circulating tumor DNA (ctDNA) has a short half-life (&lt;2 hours) which may permit real-time monitoring of tumor status. This single-institution study aimed to assess the feasibility of rapid treatment response evaluation through serial short-interval ctDNA testing. Methods: Patients with gastrointestinal (GI) cancer undergoing immune checkpoint inhibitor (ICI)-based therapy were included. A personalized, tumor-informed ctDNA assay (Signatera, Natera, Inc.) was used in this study. We collected samples to measure the baseline ctDNA levels on cycle 1, day 1 (C1D1) of treatment or within 14 days prior to C1D1. A second ctDNA sample was obtained after 14-21 days depending on the cycle length of the treatment regimen employed (on cycle 2, day 1 [C2D1]). Changes in ctDNA levels between baseline and C2D1 were recorded, as well as the tumor response at the first radiographic assessment. Patients achieving partial response (PR) or better, or stable disease (SD) with tumor shrinkage supporting continuation of same treatment were considered responders. Results: The study cohort consisted of 14 patients aged 36-89 years (median age 66); 5 patients were female. Tumor types included advanced colorectal (n=5) and gastroesophageal (n=9) cancers. Treatments consisted of pembrolizumab alone (n=5), ICI + chemotherapy combinations (n=8), and regorafenib plus nivolumab (n=1). Baseline ctDNA levels were obtained on C1D1 in 9 patients, with the remaining 5 patients having baseline measurements within 14 days before C1D1. All patients had the second ctDNA level drawn on C2D1. The median interval between C1D1 and the first radiographic response assessment was 61 days (range, 45-84). A reduction in ctDNA levels by 50% or more (range: 66-100%) was observed in 9 patients (64%) after one cycle of treatment. All 9 patients were classified as responders at the time of first radiographic assessment: 7 with PR and 2 with SD but significant tumor shrinkage leading to continuation of the same treatment. In 3 patients (21%), ctDNA levels increased (range: 20-500%), correlating with progressive disease (PD) on first assessment scan. Two patients showed increased ctDNA levels of 82% and 22% after one cycle of treatment but achieved PR and SD, respectively. In both patients, however, the 3rd ctDNA level drawn before the first assessment scan dropped by &gt;90%. Overall, short-interval ctDNA kinetics correlated with treatment response in 12 of 14 patients (86%), with a binomial test p = 0.0065. Conclusions: Short-interval ctDNA kinetics demonstrates a strong correlation with radiographic tumor response and clinical benefit in GI cancer patients receiving ICI-based treatments, providing early signal of tumor response. This approach has the potential to guide treatment decisions if validated in larger prospective studies.

P-2249. Validation of 2-deoxy 2-[18F]fluorocellobiose as a Novel Metabolic PET Radiotracer for Specific Detection and Monitoring of Aspergillus Infections In Vivo

Abstract Background A major hurdle to the diagnosis of invasive fungal infections (IFIs), mainly caused by Aspergillus fumigatus (Af), remains the lack of timely and definite diagnosis. Several filamentous fungi express β-glucosidases (BGL) which convert cellobiose, a disaccharide, into 2 glucose units. Exploiting this pathway, we developed a novel tracer, 2-deoxy 2-[18F]fluorocellobiose (FCB) and showed it can specifically detect Af infections in vivo, with minimal background signal and radioactivity accumulation in live Af infection (Fig 1), but not in bacterial infection or sterile inflammation. In this study, we expanded the use of FCB to evaluate treatment response in Af infected mice. Specific detection of Af infection by FCB-PET imaging (A) Mechanism of action: FCB in the presence of β-glucosidase (BGL) producing fungi such as A. fumigatus (Af), is metabolized into FDG and glucose molecules. The resulting FDG is retained within the lesions containing metabolically active fungi. (B) Representative static PET/CT images at 120 mins after ∼7.4-9MBq bolus injection of FCB in mouse myositis models with live (right thigh) or heat-killed (HK) (left thigh) A. fumigatus (n=11) . The signal from the urinary bladder has been removed from the images for clarity purposes. SUVmean values show significantly higher PET signal in the site of live Af infection. ****, p &amp;lt; 0.0001 (unpaired t-test). GMS staining of tissues with live (hyphal structures) and HK (spores) fungi (Accepted for publication). Methods FCB was synthesized by enzymatic conversion of 2-deoxy-2-[18F]fluoroglucose (FDG). Mice were immunosuppressed using cyclophosphamide. Myositis infections were induced by intramuscular thigh injection of live Af conidia. Daily Voriconazole (VCZ) treatment was started on D1 for 3 weeks (40mg/kg, IP). Longitudinal FCB-PET was performed (D3, D14, D21) and standardized uptake values (SUVmean) were calculated. At the study endpoint, tissues were collected for Grocott’s Methenamine Silver (GMS) staining. Our results were compared to a similar previous treatment study where we used IV Amphotericin B (AmB) (15mg/kg). Evaluation of treatment response by FCB-PET imaging (A) Representative static PET/CT images of FCB uptake and SUV mean values in A. fumigatus myositis models (n=5) at different time-points after amphotericin B (AmB) treatment showing no appreciable decrease in PET signal over time. GMS staining of the thigh muscles at the terminal time-point show proliferating hyphae indicating sub-clinical efficacy of treatment. (B) Representative static PET/CT images of FCB uptake in A. fumigatus myositis models (n=12) at different time-points after voriconazole (VCZ) treatment showing decreased PET signal over time. SUVmean values show significant decrease in signal corresponding to the live infection focus (ANOVA mixed effects model) with significant treatment effect (p&amp;lt;0.0001). ** p&amp;lt;0.001; *p&amp;lt;0.05. GMS staining shows minimal hyphal growth indicating good control of infection. Results FCB-PET showed the initial spread and eventual decline in Af infection in VCZ treated mice with decreasing SUVmean values on D14 and D21 showing significant treatment effect (p&amp;lt; 0.0001, ANOVA mixed effects model) (Fig 2). As expected, VCZ treatment was more effective than AmB treatment which showed sub-clinical efficacy with minimal decrease in FCB-PET signal over time. GMS staining also showed decreased proliferating hyphae in the VCZ cohort unlike the AmB treated group. Conclusion We developed a novel Af-specific PET ligand, FCB, and demonstrated its ability to non-invasively diagnose Af infection in vivo and monitor treatment effect with different antifungals. Thus, FCB can also be used for repeated efficacy testing of novel therapeutics within the same cohort of animals. FCB is synthesized from commercial FDG and is a highly translatable Af-specific PET ligand. Further usefulness in other fungal infections is being evaluated. Disclosures All Authors: No reported disclosures

Integrating Radiomics Signature into Clinical Pathway for Patients with Progressive Pulmonary Fibrosis

Interstitial lung diseases (ILDs) are a heterogeneous group of pulmonary disorders characterised by variable degrees of inflammation, interstitial thickening, and fibrosis leading to distortion of the pulmonary architecture and gas exchange impairment. There are approximately 200 different entities in this category. ILDs are commonly classified based on several criteria, including causes, clinical features, and radiological patterns. Chest HRCT is the gold standard for the recognition of lung alteration patterns underlying interstitial lung diseases (ILDs), diagnosing specific patterns, and evaluating radiologic progression. Methods based on artificial intelligence (AI) may be used in computational medicine, especially in image-based specialties such as radiology. The evolving field of radiomics offers a unique and non-invasive approach to extracting quantitative information from medical images, particularly high-resolution computed tomography (HRCT) scans. This comprehensive review explores the burgeoning role of radiomics in unravelling the intricacies of interstitial lung disease. It focuses on its potential applications in diagnosis, prognostication, and treatment response evaluation.

P1099 Simple magnetic resonance imaging markers are non-inferior measures of treatment response compared to complex disease activity scores in patients with active Crohn’s disease

Abstract Background Minimally invasive modalities have shown significant potential for monitoring disease severity and treatment response in Crohn’s disease (CD). Several magnetic resonance imaging (MRI) scoring systems have been validated in research settings. However, these calculations are time-consuming, which limit their widespread adoption in clinical practice. This analysis evaluated treatment response in patients with active CD using simple imaging markers and compared them to complex multifactorial scores. Methods A post-hoc analysis was conducted using data from a prospective, blinded, multicenter study (ClinicalTrials.gov: NCT03435016). The study included patients with endoscopically active CD and a clinical indication for medical treatment. All patients completed ileocolonoscopy (IC) and MRI-enterocolonography with intravenous contrast and diffusion-weighted sequences before and after treatment. IC served as the gold standard. Response was defined as a ≥ 50% reduction of Simple Endoscopic Score for Crohn’s Disease (SES-CD). The simple markers evaluated were bowel wall thickness (BWT) and the apparent diffusion coefficient (ADC). Measurements were performed on the most severely affected ileocolonic segment and were compared to Magnetic Resonance Index of Activity (MaRIA), Simplified MaRIA (sMaRIA), and the Clermont score. Results Forty-two patients with known CD were included in the analysis. Patient characteristics are shown in Table 1. Endoscopic response was achieved in 19 patients (45.2%) with a median SES-CD of 11.5 (interquartile range [IQR] 9-17) and 7.0 (IQR 0-13) before and after medical treatment, both P &amp;lt; 0.001. MaRIA, sMaRIA, Clermont score, BWT, and ADC all significantly improved in patients with endoscopic response compared to non-responders (P &amp;lt; 0.05). Receiver operating characteristics are shown in Figure 1. The diagnostic accuracy for the absolute difference in BTW (AUC 0.735, 95% CI 0.583-0.886) and ADC (AUC 0.753, 95% CI 0.602-0.904) appeared to be higher than MaRIA (AUC 0.595, 95% CI 0.415-0.775), P = 0.12 and P = 0.13, respectively. The relative reduction of BTW (AUC 0.761, 95% CI 0.611-0.911) trended towards higher diagnostic accuracy compared to MaRIA (AUC 0.627, 95% CI 0.448-0.806, P = 0.098). A &amp;gt; 17% relative reduction of BWT resulted in an optimal sensitivity and specificity of 73.7% (95% CI 48.8-90.9) and 82.6% (95% CI 61.2-95.0), respectively. Conclusion Repeated measurements of BWT or ADC in the most diseased ileocolonic segment appear to be non-inferior to validated scores like MaRIA and sMaRIA at determining response to medical treatment in patients with active CD. These measurements are simple to perform and do not require intravenous contrast.

P0696 ADSS: A novel AI-derived metric for quantifying disease severity and extent in ulcerative colitis

Abstract Background The Mayo Endoscopic Subscore (MES) is the prevailing standard for evaluating ulcerative colitis (UC) severity endoscopically, but correlates poorly with response to treatment. A comprehensive assessment encompassing both severity and extent is critical for monitoring treatment response in UC. Here we present the Aggregated Disease Severity Score (ADSS), a novel metric quantifying inflammation severity and extent in UC derived from the Ulcerative Colitis Severity Classification and Localized Extent (UC-SCALE) algorithm. Methods UC-SCALE was trained using 4,306 sigmoidoscopy videos from phase III etrolizumab clinical trials and consists of 1) preprocessing algorithms, 2) scoring algorithm that assigns MES score (0-3) to each frame, and 3) camera localization algorithm which maps each frame to an anatomical location. The ADSS is calculated by dividing the colon into 10 equal segments based on the location. An average MES score is computed for each segment, and these scores are summed to yield the ADSS (Figure 1 top) which ranges from 0 (all segments healthy) to 30 (all segments severely affected). Results UC-SCALE closely agrees (QWK = 0.83) with centrally-read MES. However, UC-SCALE’s spatially-resolved disease severity information showed clear treatment effects in groups of patients classified as endoscopic non-responders by the central reading score (CR); this was also reflected in the ADSS which showed decreased disease severity between screening and end-induction timepoints, but the CR was unchanged (Figure 1 bottom). Importantly, ADSS was more strongly correlated with fecal calprotectin than centrally-read MES (rADSS = 0.50 vs rCR = 0.37; Steiger’s Z-test Z = 3.10, p = 0.002). Conclusion UC-SCALE and ADSS provide a holistic disease evaluation by capturing both the severity and extent of inflammation. Together, these tools can be employed to improve the sensitivity of treatment response evaluation in clinical trials.

Clinical Experience with TNF Inhibition and Longitudinal Image Monitoring in Osseous Sarcoidosis.

In this case series, we present longitudinal imaging surveillance of 6 cases of osseous sarcoidosis, each of which was effectively treated with tumor necrosis factor (TNF) inhibition. We identified 6 patients from Brooke Army Medical Center with osseous sarcoidosis, who were treated with TNF inhibition and followed with longitudinal imaging studies. Cases of osseous sarcoidosis were defined as having pathologic evidence of noncaseating granulomas on bone biopsy and evidence of osseous lesions on imaging attributable to sarcoidosis by the radiologist, treating clinician, and reviewer. Clinical data were obtained through review of the military electronic medical record. Longitudinal imaging with positron emission tomography/computed tomography, magnetic resonance imaging, and bone scintigraphy assisted in the identification of active disease and clinical remission. Imaging progression of asymptomatic lesions was associated with the eventual development of bone pain 1 to 3 years later. Clinical remission was achieved in all six cases of osseous sarcoidosis and effective doses for TNF inhibition were adalimumab 40 mg subcutaneously every 1 to 2 weeks and infliximab 5 mg/kg every 6 to 8 weeks. Time to complete imaging response ranged from 3 to 8 months. Longitudinal imaging with bone scintigraphy, positron emission tomography/computed tomography, and magnetic resonance imaging demonstrated several benefits including evaluation for occult disease, surveillance of asymptomatic lesions, and evaluation of treatment response. TNF inhibition with adalimumab or infliximab was successful in all cases, and complete resolution of osseous lesions was demonstrated in 5 of 6 patients. Discontinuation of TNF inhibition led to disease recurrence in 2 cases, which prompted the use of long-term immunosuppressive therapy in all treated patients.

Nuclear medicine approaches in the field of oncologic pediatric surgery and review the risk factors for pediatric thyroid nodules

Imaging methods used in nuclear medicine are non-invasive and can be applied to all pediatric age groups, including the neonatal period. F-18 FDG-PET/CT is used for staging, evaluation of treatment response, detection of metastases, and follow-up of various pediatric malignancies. In addition, the incidence of thyroid cancer in childhood has recently increased. In this review, we examined the F-18 FDG PET/CT imaging method that guide the management of the most common malignancies in children. We also discuss in detail the risk factors used in the diagnosis of thyroid cancer frequently encountered by pediatric surgeons.

THE EFFICACY AND SAFETY OF SECUKINUMAB 150MG REGIMEN IN TREATING PATIENTS WITH PSORIASIS VULGARIS

Objectives: Evaluate the effectiveness and safety of secukinumab 150mg subcutaneous injection regimen in treating patients with moderate to severe psoriasis vulgaris. Subjects and methods: Prospective clinical trial on 32 patients with moderate to severe psoriasis. Patients were treated with secukinumab 150mg subcutaneous injection regimen for weeks 0, 1, 2, 3, 4, 8, 12, 16. Evaluate treatment response with PASI, DLQI and IGA 2011 and record adverse effects during 16 weeks. Results: After 16 weeks of treatment, PASI and DLQI gradually decreased during the period. The proportion of PASI 75 responses was highest at week 12 with 90.7%, while the proportion of PASI 90 and PASI 100 responses increased continuously until week 16, with 75% and 25% at week 16 respectively. There is a correlation between patients’ weight and the efficacy of the regimen. 3 cases (9.4%) experienced adverse effects, including fatigue, nasopharyngitis and shingles. Conclusion: Secukinumab 150mg regimen showed as an effective therapy with minor adverse events in the treatment of patients with moderate to severe psoriasis vulgaris. Received 11 November 2023Revised 30 December 2023Accepted 28 February 2024

Correlation on metabolic complete response on positron emission tomography and pathological complete response in patients with breast cancer after neoadjuvant chemotherapy.

The use of neoadjuvant chemotherapy in treating breast cancer has expanded in recent years. There was increased interest in using positron emission tomography (PET) for the evaluation of treatment response. We aimed to study the accuracy of metabolic complete response (mCR) on PET scan in predicting pathological complete response (pCR) after neoadjuvant treatment. Between January 1, 2014 and June 30, 2019, 356 consecutive patients who completed neoadjuvant treatment underwent PET scan before surgery. 207 patients (58.1%) achieved mCR and 128 patients (36.0%) achieved pathologic CR. Among mCR patients, 101 (48.8%) had pCR. Among pCR patients, 27 (21%) did not achieve mCR on PET. The overall sensitivity of predicting pCR with mCR was 78.9% and specificity of 53.5%. The overall accuracy was 0.691 by area under the receiver operating characteristic curve (AUC). Analysis using mCR to predict breast/axilla pCR had a sensitivity of 76.2%/67.9%, specificity of 54%/62.1%, and AUC of 0.682/0.675, respectively. Sensitivity and specificity were highest among HR-/HER2+ (87.1% and 57.1%), followed by HR+/HER2- (85% and 59.6%) and triple negative (82.1% and 54.1%) and the lowest were HR+/HER2+ (triple positive) (69.4% and 40.3%). There was little difference in sensitivity and specificity among the high and low Ki67 proliferation index (78.3% vs. 75% and 52.1% vs. 62.5%). PET was useful in evaluation of tumor response to neoadjuvant chemotherapy especially in the HR-HER2+ subtype. However, its accuracy was not high enough to replace surgery.

Computed tomography Hounsfield unit values as a treatment response indicator for spinal metastatic lesions in patients with non-small-cell lung cancer: a retrospective study in Japan.

A retrospective study. This study aimed to determine the impact of increased Hounsfield unit (HU) values for metastatic spinal lesions measured via computed tomography on the overall survival of patients with non-small-cell lung cancer (NSCLC) and identify factors associated with increased HU values in metastatic spinal lesions. Previous studies have underscored the utility of the HU as a marker of treatment response in metastatic bone lesions. However, no prior studies have explored the relationship between HU changes in response to treatment and overall survival in patients with NSCLC. This study included a total of 85 patients between 2016 and 2021. Nonsurgical treatments were provided by the respiratory medicine department. HU values for metastatic spinal lesions were evaluated upon diagnosis of spinal metastasis (baseline) and at 3, 6, and 12 months thereafter. Patients were then divided into two groups based on the median HU increase from baseline to 3 months. Overall survival was assessed using the Kaplan-Meier method. Based on the median change in HU value (124), 42 and 43 patients were categorized into the HU responder and non-responder groups, respectively. The median overall survival was significantly longer in the HU responder group than in the HU non-responder group (13.7 months vs. 6.4 months, p <0.001). Multiple linear regression analysis revealed that the use of antiresorptive agents and molecularly targeted therapies were factors significantly associated with an increase in HU. An increase in HU values for metastatic spinal lesions after 3 months of treatment was correlated with a significantly longer overall survival in patients with NSCLC. Thus, HU measurements may not only serve as an easy and quantitative approach for evaluating treatment response in metastatic spinal lesions but also predict overall survival.

Evaluation of EGFR-TKIs and ICIs treatment stratification in non-small cell lung cancer using an encrypted multidimensional radiomics approach

BackgroundRadiomics holds great potential for the noninvasive evaluation of EGFR-TKIs and ICIs responses, but data privacy and model robustness challenges limit its current efficacy and safety. This study aims to develop and validate an encrypted multidimensional radiomics approach to enhance the stratification and analysis of therapeutic responses.Materials and methodsThis multicenter study incorporated various data types from 506 NSCLC patients, which underwent preprocessing through anonymization methods and were securely encrypted using the AES-CBC algorithm. We developed one clinical model and three radiomics models based on clinical factors and radiomics scores (RadScore) of three distinct regions to evaluate treatment response. Additionally, an integrated radiomics-clinical model was created by combining clinical factors with RadScore. The study also explored the association between different EGFR mutations and PD-1/PD-L1 expression in radiomics biomarkers.FindingsThe radiomics-clinical model demonstrated high performance, with AUC values as follows: EGFR (0.884), 19Del (0.894), L858R (0.881), T790M (0.900), and PD-1/PD-L1 expression (0.893) in the test set. This model outperformed both clinical and single radiomics models. Decision curve analysis further supported its superior clinical utility. Additionally, our findings suggest that the efficacy of EGFR-TKIs and ICIs therapy may not depend on detecting a singular tumor feature or cell type.ConclusionThe proposed method effectively balances the level of evidence with privacy protection, enhancing the study’s validity and security. Therefore, radiomics biomarkers are expected to complement molecular biology analyses and guide therapeutic strategies for EGFR-TKIs, ICIs, and their combinations.

Tremelimumab plus durvalumab prior to chemoradiotherapy in unresectable, locally advanced non-small cell lung cancer: the Induction trial.

The phase I Induction trial (NCT04287894) assessed the feasibility and safety of induction immunotherapy (IIT) prior to concurrent chemoradiotherapy (cCRT) in patients with locally advanced non-small cell lung cancer (NSCLC). Patients with unresectable stage II/III NSCLC were eligible for inclusion. Patients received either one cycle of tremelimumab (75mg) with two cycles of durvalumab (1500mg) in cohort I, one cycle of tremelimumab (300mg) with two cycles of durvalumab in cohort II or one cycle of tremelimumab (300mg) with one cycle of durvalumab in cohort III. After IIT, a comprehensive radiological and pathological restaging was performed followed by cCRT. The combined primary endpoint was feasibility and safety of IIT-cCRT. Fifteen of seventeen included patients were treated per-protocol. IIT-cCRT was completed in 13/15 of the patients within the predefined feasibility criteria. Grade ≥3 immune-related adverse events (irAEs) occurred in 7/15 patients, of which 6 were treated in the high-dose tremelimumab cohorts, thereby violating the safety criteria in cohorts II and III. The low-dose tremelimumab cohort (I) complied with safety criteria. Eleven patients had multilevel N2 or N3 disease at baseline, eight of these patients were downstaged to either N0/1 or single level N2 after IIT. Multiparametric MRI accurately identified nodal downstaging in 7/7 patients. Induction with high-dose tremelimumab plus durvalumab prior to cCRT in unresectable locally advanced NSCLC was associated with unacceptable toxicity, although ITT resulted in clinically relevant nodal downstaging in 8/11 of patients with baseline multilevel N2 or N3 disease. Multiparametric MRI showed potential evaluating treatment response.

CT perfusion and MRI: A combined approach for hepatocellular carcinoma diagnosis and follow-up after locoregional treatment.

CT liver perfusion (CTLP) has been well validated for hepatocellular carcinoma (HCC) detection, characterization, and treatment response evaluation. However, its role in HCC management algorithms remains unclear. This study aims to assess the diagnostic performance of CTLP alone or as an adjunct to MRI in patients considered for- or undergoing locoregional treatment for HCC. Thirty-nine patients under HCC surveillance (36 male, 31 cirrhotic, 16 pretreatment, 19 post-transarterial chemoembolization, 2 post-ablation) underwent MRI and CTLP in a single center within a 45-day interval. Two readers identified and characterized all observations on MRI using Liver Imaging Reporting and Data System (LI-RADS) v2018 criteria. CTLP assessment was based on Mean Slope of Increase (MSI), Time To Peak (TTP), Hepatic arterial Blood Flow (HaBF) and Hepatic Arterial Fraction (HAF) maps and established cut-offs. Diagnostic performance of MRI, CTLP, and their combination was evaluated for treated and untreated lesions using imaging or pathology as reference standard. Of the total 33 treated and 61 untreated lesions, 13 and 41 were considered viable HCCs. CTLP demonstrated 75.9 % sensitivity and 95 % specificity compared to 72.2 % and 100 % for MRI (p > 0.05). Combining both modalities increased sensitivity to 85.2 % (p < 0.05) and maintained specificity at 97.5 % (p > 0.05). The combined approach led to an LR category change in 5 treated and 19 untreated lesions and affected management in 5 cases. CTLP and MRI have comparable diagnostic performance for HCC. A combined approach improves sensitivity, without sacrificing specificity. This approach might enable more efficient patient selection for early and individualized loco-regional treatment.

Emerging biomarkers in major depressive disorder: Diagnostic, prognostic, and therapeutic implications

Recent advancements in biomarker research for the diagnosis, prognosis, and treatment strategies of major depressive disorder (MDD) have yielded significant findings that warrant documentation. The clinical demand for biomarkers persists due to the limited accuracy and efficiency of subjective diagnostic approaches. This review scrutinized research papers related to MDD biomarkers published between January 2011 and till July 2024, focusing exclusively on human studies with statistically significant results. The compiled biomarkers encompass cellular membrane receptors, cytoplasmic organelles, and genomic and epigenomic intranuclear markers. Cell surface molecular receptors implicated in MDD pathogenesis include brain-derived neurotrophic factor (BDNF) receptors, N-methyl D-aspartate receptors (NMDAR), and interleukin (IL) receptors. Endogenous compounds with diagnostic and prognostic potential, such as L-carnitine and alpha-L-carnitine, have also been identified. Transcriptomic biomarkers, including mRNA expression levels of the BDNF, IL-1&amp;beta;, macrophage migration inhibitory factor, and tumor necrosis factor-alpha (TNF-&amp;alpha;), have demonstrated utility in MDD management. MicroRNAs (miRNAs), the endogenous molecules that alter the structure of mRNA, show potential for diagnosis and treatment outcome prediction, with miR-221-3p, miR-129-5p, miR-134, and miR-184 emerging as key candidates for MDD monitoring. Long non-coding RNAs (lncRNAs), such as GSK3&amp;beta;AS1, GSK3&amp;beta;AS2, and GSK3&amp;beta;AS3 have been investigated for the evaluation of disease severity and treatment response. Most recently, the pathological role of circular (circRNA) and DNA methylation in MDD has also been documented. The rs155979 polymorphism in the lncRNA NOTHSAT102891 was significantly associated with depression and risk of suicide. The data compiled in this review aim to guide further research in the quest for biomarkers that will improve the management of MDD.

Primary staging with 2[18F]-FDG-PET/CT and -PET/MRI and radiotherapy response evaluation with MRI in uterine cervical cancer: an interim analysis of a prospective clinical trial

BackgroundIn uterine cervical cancer (UCC), tumour staging is performed according to the 2018 International Federation of Gynecology and Obstetrics (FIGO) system, where imaging is incorporated, or the more generic Tumour Node Metastasis (TNM) classification. With the technical development in diagnostic imaging, continuous prospective evaluation of the different imaging methods contributing to stage determination is warranted. The aims of this interim study were to (1) evaluate the performance of radiological FIGO (rFIGO) and T staging (rT) with 2-fluorine-18-fluoro-deoxy-glucose (2[18F]-FDG)-positron emission tomography with computed tomography (PET/CT) and with magnetic resonance imaging (PET/MRI), compared to clinical FIGO (cFIGO) and T (cT) staging based on clinical examination and conventional imaging, in treatment-naïve UCC, and to (2) identify possible MRI biomarkers for early treatment response after radiotherapy.MethodsTen consecutive patients with newly diagnosed UCC from the prospective PRODIGYN (Prognostic and Diagnostic Added Value of Medical Imaging in Staging and Treatment Planning of Gynecological Cancer) study (ethical approval number 2022-04207-01; NCT05855941) were included. Study participants underwent 2[18F]FDG-PET/CT and -PET/MRI, and an additional MRI one week after radiotherapy. Agreement between rFIGO and cFIGO was analysed using Cohen’s kappa. Differences in rFIGO between 2[18F]FDG-PET/CT and -PET/MRI were evaluated with Wilcoxon signed ranks test, and added value of rFIGO for metastasis assessment was demonstrated with descriptive statistics.ResultsIn 2/10 patients, a higher stage was obtained with rFIGO compared to cFIGO, where presence of metastases led to upstaging. In 3/10, rFIGO was lower than cFIGO, and in 5/10 rFIGO and cFIGO were similar. Degree of agreement between rFIGO and cFIGO was poor, (κ = 0.091, p < 0.005) with 2[18F]FDG-PET/CT and (κ = − 0.010, p > 0.05) with FDG/PET/MRI). There was no significant difference between 2[18F]FDG-PET/CT and -PET/MRI for rFIGO (p = 0.18), or rT stage assessment (p = 0.32). MRI-derived tumour volume and apparent diffusion coefficient (ADC) were most affected on MRI one week after radiotherapy.ConclusionsOur results indicate that there is an added value of rFIGO staging with 2[18F]FDG-PET/CT and -PET/MRI compared to clinical examination and conventional radiology, for metastasis assessment in treatment-naïve UCC. In early treatment response evaluation with MRI, ADC and tumour volume may be predictive parameters of interest in future prognostic analyses.Trial registrationClinical Trials, NCT05855941. Registered 02 May 2023, https://clinicaltrials.gov/study/NCT05855941?term=NCT05855941&rank=1.