Assessment Of Clinical Response Research Articles

Clinical validation of the Northstar Response: A novel quantitative methylation ctDNA monitoring assay for advanced GI cancer treatment response.

839 Background: Circulating tumor DNA (ctDNA) is a promising tool for monitoring treatment response but is challenged by pan-cancer quantification and consistent outcome correlations. Northstar Response (NSR) quantifies >500 cancer specific methylated loci, offering a reflection of disease burden and clinical response. Methods: We present a prospective observational study to evaluate the clinical utility of NSR. Patients with advanced GI cancers had serial ctDNA assessed at baseline and during systemic treatment with correlations to radiographic or clinical response. Tumor methylation scores (TMS) were expressed as Log10 values and a mixed-effects model evaluated clinical assessment correlations. Results: 73 patients with locally advanced or metastatic GI cancers were analyzed. Among these, 35 (47.9%) had at least four ctDNA assays and all had radiographic or clinical response assessments. The median age was 66 years (± 8.5), with most being male (67.1%) and White (74.0%). Table 1 shows the case distribution. Baseline TMS had significant variation (p=0.023), but was measurable across all tumor types. CRC exhibited the highest mean TMS-log10 while biliary and pancreatic cancers had the lowest. Cases with both primary and metastatic lesions had a higher mean TMS-log10 than cases with either primary tumors alone or metastatic lesions alone (3.4 vs. 3.0). Compared to stable and responsive disease, TMS changes correlated with progressive disease, with a coefficient of 0.48 at the third collection time point (p=0.05). However, 23/73 (32%) cases were without an on-treatment TMS timepoint (OTT) due to rapid progression (average time to death of 24 vs. 103 days for patients with OTT). In exploratory modeling of TMS relative to RECIST-like treatment response for those with OTT, NSR evaluations were associated with response assessments (p<0.04, Fisher’s Exact Test). Conclusions: TMS was consistently measurable but varied across tumor types and correlated with disease burden. TMS changes appeared associated with response assessments when accounting for rapid progressors. Additional analyses are ongoing and will be presented. Baseline study cohort characteristics. Characteristic HCCN = 25 (34%) BTC N = 12 (16%) EGAN = 12 (16%) CRCN = 11 (15%) PDACN = 8 (11%) Other GI N = 5 (7%) p-value Age Median (25% to 75%) 67 (63 - 76) 68.5 (62.3 – 75.5) 73.5 (62.5 – 75.3) 54 (39.5 – 60) 67.5 (55.5 – 76.3) 60 (57 – 63) 0.008 Baseline TMS Log10 Median (25% - 75%) 3.2 (2.3 – 3.9) 2.5 (2.1 – 3.4) 3.2 (2.2 – 3.8) 4.4 (3.5 – 5) 2.5 (1.9 – 3.3) 4 (3.4 – 5.2) 0.023 Primary tumor present 12 (48%) 8 (66.7%) 12 (100%) 6 (54.5%) 7 (87.5%) 4 (80%) 0.015 First line therapy vs. not 23 (92%) 5 (41.7%) 5 (41.7%) 6 (54.5%) 3 (37.5%) 5 (100%) 0.001 Progressive disease 16 (64%) 4 (33.3%) 9 (75%) 5 (45.5%) 3 (37.5%) 4 (80%) 0.2 Death 13 (52%) 3 (25%) 9 (75%) 7 (63.6%) 3 (37.5%) 2 (40%) 0.2 Kruskal-Wallis rank sum test; Fisher’s exact test.

Abstract P021: Countering adenosine (ADO) in rectal cancer to improve RT responses to immune checkpoint blockade: a trial to test the safety and efficacy of PD1 (AB122) and ADO dual receptor (AB928) antagonists with chemotherapy after short-course RT

Abstract Background: Rectal cancer (RC) is unresponsive to single agent immune checkpoint blockade (ICB), with the exception of microsatellite instability (MSI) high tumors. Neoadjuvant radiotherapy (RT), however, is a standard treatment for locally advanced RC. A recent analysis of RC showed that upregulation of genes reflecting an increased T cell-inflamed and IFN-I response in post-RT samples compared with pre-RT biopsies correlated with pathological responses. The efficacy of combining RT with ICB in RC remains a focus of several ongoing and recently reported clinical trials. Extracellular adenosine (eADO) signaling, an important immunosuppressive pathway in RC, may hinder immune activation as TCGA and our preclinical data, respectively, suggests that eADO generation and signaling is elevated at baseline and exacerbated by RT. In mouse models, the inhibition of eADO generation improved systemic responses to ICB in otherwise refractory tumors. HypothesisWe hypothesize that inhibition of ADO signaling in RC is safe and an effective method to enhance RT-induced anti-tumor T cell responses as a means to sensitize RC to RT and anti-PD1 therapy. Brief Methods: NCT05024097, PANTHER RC trial, is a prospective phase I-II neoadjuvant study in patients with locally advanced RC. Patients receive upfront (wk 1) SC-RT (25 Gy in 5 fx) to the pelvis in combination with the dual A2aR/A2bR (adenosine receptors) inhibitor etrumadenant (AB928). Chemotherapy (wks 3-15), mFOLFOX x 6 cycles, is given with etrumadenant and anti-PD1 antibody zimberelimab (AB122). All patients undergo clinical response assessment (weeks 17-20) followed by watch and wait (if cCR) or total mesorectal excision for pathologic response assessment. The primary endpoint is the proportion of patients who achieve a CR. Secondary endpoints include 3-year disease-related treatment failure and 5-year overall survival. Part I is a modified 3+3 safety run-in for etrumadenant plus SC-RT. Part II is an open label single arm Simon’s 2-stage optimal design. With a sample size of 27 patients (stage 1 = 15 patients and stage 2 = 12 patients) the trial is powered to detect a CR rate of 25% or less versus the atlernative, at least 45%. Results: To date 21 patients have enrolled. One of six patients accrued to part I experienced a grade 3+ treatment related toxicity. A CR was observed in one of five (20%) evaluable patients. In part II, the first eleven of fifteen accrued patients to stage 1 completed treatment and were assessed for response. A CR rate of 82% (4 pCRs, 5 cCRs, 2 pPRs) was observed. The trial is anticipated to proceed to stage 2 and accrue an additional twelve patients (27 total). Conclusion: The preliminary responses are promising and patient enrollment is ongoing. Tumor biopsies, blood specimens, and stool samples before and after RT will be comprehensively analyzed to determine the immune contexture at baseline, during, and after therapy. Correlative studies will help determine whether RT with ADO signaling blockade produces anti-tumor T cells capable of achieving CRs in locally advanced RC. Citation Format: Encouse Golden, Sandra Demaria, Nir Ben Chetrit, Mehraneh Dorna Jafari, Manish Shah, Silvia Formenti.Countering adenosine (ADO) in rectal cancer to improve RT responses to immune checkpoint blockade: a trial to test the safety and efficacy of PD1 (AB122) and ADO dual receptor (AB928) antagonists with chemotherapy after short-course RT.[abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr P021

On-treatment dynamics of circulating extracellular vesicles in the first-line setting of patients with advanced non-small cell lung cancer: the LEXOVE prospective study.

Extracellular vesicle (EV) monitoring can complement clinical assessment of cancer response. In this study, patients with advanced non-small cell lung cancer (NSCLC) undergoing osimertinib, alectinib, pembrolizumab or platinum-based chemotherapy ± pembrolizumab were enrolled. EVs were characterized using Bradford assay to quantify the circulating cell-free EV protein content (cfEV), and dynamic light scattering to assess Rayleigh ratio excess at 90°, z-averaged hydrodynamic diameter and polydispersity index. A total of 135 plasma samples from 27 patients were collected at baseline (T0) and at the first radiological restaging (T1). A ∆cfEV < 20% was associated with improved median progression-free survival (mPFS) in responders versus non-responders. Specifically, cfEV responders on pembrolizumab had a significantly better mPFS (25.2 months) compared to those on chemotherapy plus pembrolizumab (6.1 months). EGFR-positive cfEV responders also experienced longer mPFS compared to cfEV non-responders (35.1 months, 95% CI: 14.9-35.5 vs. 20.8 months, 95% CI: 11.2-30.4). This study suggested that monitoring circulating EV could provide valuable insights into treatment efficacy in NSCLC, particularly for patients receiving pembrolizumab or osimertinib.

How accurate are machine learning models in predicting anti-seizure medication responses: A systematic review.

Current epilepsy management protocols often depend on anti-seizure medication (ASM) trials and assessment of clinical response. This may delay the initiation of the ASM regimen that might optimally balance efficacy and tolerability for individual patients. Machine learning (ML) can offer a promising tool for efficiently predicting ASM response. The objective of this review is to synthesize the available information about the effectiveness and limitations of ML models in predicting and classifying the response of patients with epilepsy to ASMs, and to assess the impact of various data inputs on prediction performance. We conducted a comprehensive search of studies utilizing ML models for ASM response prediction using PubMed and Scopus up until November 2024. The review included 37 studies. Various data types, including clinical information, brain MRI, EEG, and genetic data, are useful in predicting responses to ASMs. Tree-based ML algorithms and Support Vector Machines are the most used models. Reported results vary widely, with certain models achieving near-perfect accuracy and others performing similar to random classifiers. The review also highlights the limitations of this research field, especially concerning the quality and quantity of data. The findings indicate that while ML models show great promise in predicting ASM responses in epilepsy, further research is required to refine these models for practical clinical application. The review underscores both the potential of ML in advancing precision medicine in epilepsy management and the need for continued research to improve prediction accuracy.

Terbinafine in acrylic polymer for the treatment of onychomycosis in hemodialysis patients: a phase II clinical trial.

Onychomycosis is a nail infection caused by dermatophyte fungi, non-dermatophyte fungi, and yeast. Patients with chronic kidney disease on dialysis are part of the population that presents higher rates of this disease, mainly due to immunosuppression. Among patients with chronic kidney disease on dialysis, the treatment of onychomycosis is complex, mainly due to the limitations imposed by comorbidities. In this context, the study evaluated the safety and potential efficacy of a treatment that combines nail debridement with the use of acrylic gel nails carrying terbinafine at a concentration of 2%. Patients from the Hemodialysis Center of the São Francisco de Assis University Hospital in Bragança Paulista, São Paulo, Brazil were included. Those had hallux onychomycosis with clinical forms whose treatment involved the need for nail debridement. After the debridement procedure, a nail prosthesis made with acrylic reconstruction gel and 2% terbinafine was applied. The procedure was renewed every 2 weeks (~14 days) for 11 months. The evolution was monitored with measurements of the normal-appearing nail plate and photographs. Direct mycological examination and fungal culture were performed at the beginning of the study and 30 days after applications were interrupted. Assessment of clinical response, clinical cure, mycological cure, and complete cure was performed at the end of the study. All participants answered a questionnaire about their perception of the treatment. Out of the 155 patients on hemodialysis, 64/155 (41.3%) individuals were identified with symptoms suggestive of onychomycosis in the halluces after clinical analysis. Among them, 35/64 (54.7%) individuals presented a positive direct mycological examination and underwent fungal culture to identify the etiological agent. In this group of patients, 24/35 (68.6%) individuals who presented clinical forms whose treatment involved the need for nail debridement were selected. Only 15/24 (62.5%) individuals completed the study. Among the study participants, 5/15 (33.3%) still presented positive fungal culture in the presence of a negative direct mycological examination and 1/15 (6.7%) presented a positive direct mycological examination, but with a negative culture. Among those with a positive fungal culture, 3/15 (20.0%) participants presented microorganisms different from those isolated in the initial exams. Regarding cure, 5/15 (33.3%) participants showed a clinical response, 4/15 (26.7%) clinical cure, and 3/15 (20.0%) complete cure. No patient presented an allergic reaction or local irritation caused by the material used in the treatment. There were accidental superficial ulcerations caused by the electric sandpaper; however, no wound developed secondary infection. No participant reported discomfort due to the nail prosthesis use, 3/15 (20.0%) reported a feeling of discomfort caused by the vibration of the electric file and 12/15 (80.0%) reported the perception that their nails had a better appearance during treatment with nail prosthesis made with acrylic reconstruction gel and 2% terbinafine. The application of 2% terbinafine in acrylic reconstruction gel for the manufacture of nail prostheses applied after debridement of moderate and severe forms of onychomycosis showed low efficacy as an isolated treatment in patients on dialysis due to chronic kidney disease. On the other hand, most patients had a good perception of the appearance of their nails during treatment, even when it did not result in apparent clinical improvement or complete cure.

Neoadjuvant chemoradiation for down staging of locally-advanced rectal cancer, and assessment of clinical response with digital rectal examination, magnetic resonance imaging and colonoscopy

Background: In this era of total neoadjuvant treatment (TNT) followed by rectal preservation non-operative management (NOM) or wait and watch (WW) approach for non-metastatic locally-advanced rectal cancer (LARC), reliable and reproducible response evaluation to neoadjuvant therapies forms the cornerstone. Through this study, we try to evaluate clinical response of locally-advanced rectal cancer to neoadjuvant chemoradiation (CRT) in terms of downstaging and total mesorectal excision (TME), and the accuracy of digital rectal examination (DRE), magnetic resonance imaging (MRI) and colonoscopy in the assessment of clinical response to neoadjuvant CRT. Methods: Histologically proven locally advanced rectal adenocarcinoma patients, after pretreatment evaluation, were considered for neoadjuvant chemoradiation, i.e., intensity-modulated radiation therapy (IMRT) with 5-fluorouracil (5-FU) and leucovorin-based concurrent chemotherapy. Patients were evaluated 6-8 weeks after completion of CRT and clinical response assessed by means of DRE, colonoscopy and MRI of pelvis. Following surgery, pathological response was assessed on the final histopathological examination (HPE). Results: Twenty-two patients were accrued for this protocol, of which, 15 (68.2%) were male and 7 (31.8%) were female. Downstaging and TME was achieved in 90.9% of the patients. The sensitivity of DRE, colonoscopy and MRI to detect a complete response was 66.67% and specificity was 94.74%. There were no severe toxicities or deaths reported. Conclusions: Neoadjuvant concurrent chemoradiotherapy with bolus 5-FU and leucovorin is an accepted modality of treatment for locoregionally-advanced rectal cancer, which offers higher rates of downstaging and TME. Digital rectal examination, colonoscopy and MRI together can be reliably used to assess response following neoadjuvant CRT.

Deciding treatment end point in necrotizing otitis externa: validation of a standardized clinical response assessment strategy with positron emission tomography findings.

Primary: To explore criteria for treatment endpoint in NOE. Secondary: To study correlation of inflammatory markers, Erythrocyte sedimentation Rate (ESR) and C-reactive protein (CRP) with disease status. Prospective cohort study conducted in a tertiary care hospital over two years (2021-2023) consisted 28 patients with NOE. Treatment culmination point was decided based on symptoms control and correlated with PET-scan findings. Clinical response was analysed with respect to the serum inflammatory markers and PET Scan findings. There was fair degree of agreement between clinical resolution and resolution of findings on PET scan (kappa coefficient - 0.76 [95% CI; 0.40,1.00]). Inflammatory markers showed statistically significant decline with clinical resolution but failed to return to normal. Decision to terminate treatment of NOE can be reliably made on clinical grounds in patients remaining asymptomatic for three weeks. Resolution of inflammation on PET scan is in congruity with the clinical remission .

B-342 Teclistamab interference in serum protein electrophoresis and serum immunofixation electrophoresis in patients with recurrent or relapsed multiple myeloma

Abstract Background Serum protein electrophoresis (SPEP) and serum immunofixation electrophoresis (IFE) analyses are mainstays in the initial diagnosis, risk stratification, and evaluating treatment response in patients with multiple myeloma (MM) in accordance with the International Myeloma Working Group criteria. Published reports have demonstrated that therapeutic monoclonal antibodies (mAbs) used to treat MM (e.g. anti-CD38 IgG-kappa) are detectable by SPEP and IFE, which may interfere with accurate evaluation of complete response. Recently, Teclistamab (Tecvayli®; Janssen Biotech, Horsham Township, PA), a humanized bispecific IgG-lambda mAb targeting B-cell maturation antigen (BCMA) and CD3 on T cells was approved for treating patients with penta-refractory MM. In contrast with other IgG-kappa therapeutic mAbs, the degree to which Teclistamab may interfere with detection and quantification of monoclonal proteins is unknown. Therefore, we sought to assess the interference of Teclistamab therapy on routine SPEP and IFE analysis. Methods Patients treated with Teclistamab were identified by retrospective review of electronic medical records. Teclistamab (90 mg/mL) was spiked into a remnant patient sample with IgG lambda MM at a final concentration of 10 μg/mL, which corresponds to ½Cmax values in patients infused with Teclistamab. SPEP and IFE were performed using the Helena SPIFE Touch instrument. Computer-assisted densitometry was used to quantify monoclonal proteins in the gamma region of SPEP gels. Results In several patients with refractory MM treated with Teclistamab, IFE analysis revealed IgG lambda or lambda light chain monoclonal proteins, which were inconsistent with previously-identified monoclonal proteins (e.g. IgG kappa). In one patient diagnosed with IgG lambda MM, spiking 10 μg/mL Teclistamab increased M-spike abundance by approximately 0.15 g/dL when quantified by SPEP. Conclusions In patients with relapsed or refractory MM, treatment with Teclistamab may confound accurate clinical assessment of complete response by SPEP and IFE methods. Increased awareness of this preanalytical interference is necessary to guide clinical decision making.

Defining Echocardiographic Degrees of Right Heart Size and Function in Pulmonary Vascular Disease from the PVDOMICS Study.

Defining qualitative grades of echocardiographic metrics of right heart chamber size and function is critical for screening, clinical assessment, and measurement of therapeutic response in individuals with pulmonary vascular disease (PVD). In a population enriched for PVD, we sought to establish qualitative grades and prognostic value of right heart chamber size and function. We investigated 1053 study participants in the Redefining Pulmonary Hypertension through PVD Phenomics program (PVDOMICS) to determine clinical and echocardiographic differences associated with increasing pulmonary vascular resistance (PVR) severity. Right heart chamber size and function were qualitatively assessed using a percentile-based approach above the median values to create a clinical grading system for right heart adaptation. The relationship between echocardiographic categories and all-cause mortality was examined using survival analyses adjusted for potential confounders. A stepwise increase in adverse right heart remodeling was observed with a concomitant decrease in functional parameters by PVR strata (p<0.001 for all). Mild, moderate, and severe categories of right heart chamber size and dysfunction were defined using a percentile-based approach across the spectrum of PVD. During a median follow up of 2.07 years (interquartile range 1.23 - 3.01 years), 130 participants died (11.4%). Progressive PVR increase and 2DE evidence of right heart dysfunction inclusive of fractional area change, and right ventricular (RV) global longitudinal strain were independently associated with increased all-cause mortality risk in multivariate analysis adjusted for age, disease duration and male sex. In this well-characterized sample of adults with diverse etiologies and varying PVD severity, we define categories of abnormal right heart chamber size and function. Further, we demonstrate a stepwise relationship between these categories of abnormal morphology and function and all-cause mortality. Defining grades of RV dysfunction in individuals with known PVD has important clinical implications for monitoring disease progression and response to therapies.

Mycophenolate Mofetil Appears Effective for the Treatment of Patients With Refractory Crohn's Disease.

Medically refractory Crohn's disease (CD) is associated with a high risk of complications. Mycophenolate mofetil (MMF), a small molecule immunosuppressant, has limited data in patients with CD, and objective endoscopic response to MMF has not been reported. We evaluated the safety and clinical, endoscopic, and biochemical effectiveness of off-label MMF for refractory CD as monotherapy or in combination with a biologic in patients with CD. We retrospectively assessed adverse events (AEs), clinical response (Harvey-Bradshaw index), endoscopic response (simple endoscopic score in Crohn's disease), and physician global assessment at an academic medical center and county hospital. 60 patients received MMF as monotherapy (n = 40) or in combination with a biologic (n = 20) between 2008 and 2021 at a dose ranging from 1000 to 4000mg daily. Median age was 39 years and median disease duration was 12 years. All patients previously failed ≥ 1 advanced therapy (median = 4). The median MMF therapy duration was 27 weeks. 54% achieved clinical response and 19% achieved clinical remission after a mean of 19.5 weeks (SD 14.5). Endoscopic response occurred in 32%, endoscopic remission in 16%, and endoscopic healing in 4% after a mean of 46.6 weeks (SD 31.0). 48% of patients experienced AEs, most commonly mild infection, nausea/vomiting, and headache. One serious AE occurred, which was assessed as unrelated to MMF. MMF resulted in clinical, endoscopic, and biochemical benefits in some patients with refractory CD, and was tolerated by most patients. Further randomized controlled trials are needed to define optimal dosing and long-term efficacy and safety.

Assessment of clinical and pathological response to neoadjuvant chemotherapy in breast cancer according to molecular subtypes

Background. Breast cancer (BC) is the commonest tumor in women. It is the leading malignancy in world, and representing an emerging oncologic issue in all countries. In Iraq, BC cases reached 7246 in 2021by Iraqi Cancer Registry reports. Objectives. The study conducted for assessment the clinical and pathological responses to neoadjuvant chemotherapy in BC among molecular subtypes and for description the clinico-pathologic features, and patterns of BC according to molecular subtypes. Methods. A prospective study of 60 females with breast cancer histologically confirmed were enrolled. All women received neoadjuvant chemotherapy. Then all patients underwent definitive surgery including MRM+AC or BCS+AC. The patients’ demographic, the pathologic and molecular subtypes date of the primary tumor were recorded. Results. The mostly distributed age group was belong to group 46-55 yrs in 22, 36.7%. The mean age was 49.7±10.8 yrs. The IDC represented the most common histopathological types of BC. The most of cases seen in upper-outer quadrant (UOQ). The results post-chemotherapy as followed: ypTx stage reported in 32 (53.3%), ypT1 in 15 (25.0%), ypT2 in 10 (16.7%) and ypT3 in 3 (5.0%). ypN0 stage in 40 patients (66.7%), ypN1 in 11 (18.3%), ypN2 in 6 (10.0%), and ypN3 in 3 (5.0%). There was a high statistical difference between cT and ypT in pre and post-chemotherapy (P&lt;0.0001), between cN and ypN in pre and post-chemotherapy (P=0.001) and between M and ypM in pre and post-chemotherapy (P=0.002). The mass location (P=0.005) and tumor size (P = 0.011) had significantly impacted on BC responses post NACT. 18(30.0%) had clinical complete response (cCR), 32 women (53.3%) had partial response (cPR), six cases (10.0%) had stable disease, and four cases (6.7%) had progressive disease. The cCR was better seen in T1 (77.8%) than T2 (22.2%), with statistical significant difference (P=0.002). The cCR was better seen in N0 (61.1%) than N1 (38.9%), with a high statistical significant difference (P&lt;0.0001). Conclusions. The commonest age breast cancer is four to five decade. The IDC and mass situated at UOQ are the most common features of BC. Approximately, 30.0% of women have clinical complete response (cCR), 53.3% have partial response (cPR), 10.0% have stable disease, and 6.7% have progressive disease post NACT. The ER positive, PR positive, and HER2neu negative are the mostly frequent subtype recorded in this study. The cCR is better seen in T1 and N0 stages. ER+ and PR+ are more reported after NACT whereas HER2neu- is more post NACT.

Chromosomal instability is associated with prognosis and efficacy of bevacizumab after resection of colorectal cancer liver metastasis

Introduction Individualized treatment of colorectal cancer liver metastases (CRLM) remains challenging due to differences in the severity of metastatic disease and tumour biology. Exploring specific prognostic risk subgroups is urgently needed. The current study aimed to investigate the prognostic value of chromosomal instability (CIN) in patients with initially resectable CRLM and the predictive value of CIN for the efficacy of bevacizumab. Methods Ninety-one consecutive patients with initially resectable CRLM who underwent curative liver resection from 2006 to 2018 at Sun Yat-sen University Cancer Center were selected for analysis. CIN was evaluated by automated digital imaging systems. Immunohistochemistry (IHC) was performed to detect interleukin-6 (IL-6), vascular endothelial growth factor A (VEGFA) and CD31 expression in paraffin-embedded specimens. Recurrence-free survival (RFS) and overall survival (OS) were analysed using the Kaplan–Meier method and Cox regression models. Results Patients with high chromosomal instability (CIN-H) had a worse 3-year RFS rate (HR, 1.953; 95% CI, 1.001–3.810; p = 0.049) and a worse 3-year OS rate (HR, 2.449; 95% CI, 1.150–5.213; p = 0.016) than those with low chromosomal instability (CIN-L). CIN-H was identified as an independent prognostic factor for RFS (HR, 2.569; 95% CI, 1.078–6.121; p = 0.033) and OS (HR, 3.852; 95% CI, 1.173–12.645; p = 0.026) in the multivariate analysis. The protein levels of IL-6, VEGFA and CD31 were upregulated in patients in the CIN-H group compared to those in the CIN-L group in both primary tumour and liver metastases tissues. Among them, 22 patients with recurrent tumours were treated with first-line bevacizumab treatment and based on the clinical response assessment, disease control rates were adversely associated with chromosomal instability (p = 0.043). Conclusions Our study showed that high chromosomal instability is a negative prognostic factor for patients with initially resectable CRLM after liver resection. CIN may have positive correlations with angiogenesis through expression of IL-6–VEGFA axis and be used as a potential predictor of efficacy of bevacizumab.

Development of Granzyme B-targeted Smart Positron Emission Tomography Probes for Monitoring Tumor Early Response to Immunotherapy.

Granzyme B is an immune-related biomarker that closely correlates with cytotoxic T lymphocytes (CTLs), and hence detecting the expression level of granzyme B can provide a dependable scheme for clinical immune response assessment. In this study, two positron emission tomography (PET) probes [18F]SF-M-14 and [18F]SF-H-14 targeting granzyme B are designed based on the intramolecular cyclization scaffold SF. [18F]SF-M-14 and [18F]SF-H-14 can respond to granzyme B and glutathione (GSH) to conduct intramolecular cyclization and self-assemble into nanoaggregates to enhance the retention of probe at the target site. Both probes are prepared with high radiochemical purity (>98%) and high stability in PBS and mouse serum. In 4T1 cells cocultured with T lymphocytes, [18F]SF-M-14 and [18F]SF-H-14 reach the maximum uptake of 6.71 ± 0.29 and 3.47 ± 0.09% ID/mg at 0.5 h, respectively, but they remain below 1.95 ± 0.22 and 1.47 ± 0.21% ID/mg in 4T1 cells without coculture of T lymphocytes. In vivo PET imaging shows that the tumor uptake in 4T1-tumor-bearing mice after immunotherapy is significantly higher (3.5 times) than that in the untreated group. The maximum tumor uptake of [18F]SF-M-14 and [18F]SF-H-14 in the mice treated with BEC was 4.08 ± 0.16 and 3.43 ± 0.12% ID/g, respectively, while that in the untreated mice was 1.04 ± 0.79 and 1.41 ± 0.11% ID/g, respectively. These results indicate that both probes have great potential in the early evaluation of clinical immunotherapy efficacy.

Evaluation of early response in association with pathological response in patients with breast cancer receiving neoadjuvant chemotherapy.

e12628 Background: Neoadjuvant therapy (NAT) has now been widely used for patients with operable breast cancer (BC) to test drug sensitivity. Studies have indicated that early assessment of clinical response to NAT can help identify patients who are resistant to initial regimens, providing an additional opportunity to change treatment plan. However, there is a lack of evidence regarding the optimal timing for conducting early evaluations of clinical response. This prospective study was conducted to evaluate the association between early evaluation of clinical response at different timing (post 2 cycles versus post 4 cycles) and pCR post NAT, in order to determine the most appropriate timing for NAT response evaluation. Clinical evaluations using ultrasound and MRI (magnetic resonance imaging) were also compared. Methods: A prospective cohort study including BC patients who received NAT was conducted between January 2018 and December 2023. Multivariable logistic regression analysis was used to estimate the Odds Ratios (OR) and 95% confidence intervals (CI) for the clinical response evaluated at different timings in association with pCR. The heterogeneity of the associations for the post-cycle 2 and post-cycle 4 assessments was assessed. Linear regression analyses were used to assess the associations between extent of tumor reduction post 2 cycles and that post 4 cycles of NAT. Agreement of tumor measurements using ultrasound and MRI was also assessed. Results: A total of 186 BC patients were consecutively enrolled and included in this analysis. 55 (29.6%) of them achieved pCR. Partial response (PR) post 2 cycles and 4 cycles of NAT were both significantly associated with pCR post NAT, though the point estimate of association for PR post 2 cycles of NAT (OR=5.06, 95%CI:2.29-12.09) was more evident than that post 4 cycles (OR=2.79, 95%CI:1.20-7.21). Extent of tumor reduction post two cycles of NAT was highly correlated with that post four cycles (r=0.89, 95%CI=0.79-0.98, P&lt; 0.01). Poor concordance was observed between ultrasound and MRI measurements of tumor size, whether at initial diagnosis (r=0.66, adjusted r2=0.43) or after two cycles of NAT (r=0.59, adjusted r2=0.35). Among those patients who had PR post 2 cycles of NAT, tumor reduction by greater than 50% was not associated with higher probability of reaching pCR in comparison to those lower than 50% (OR=1.86, 95%CI=0.82-4.37, P=0.143). Conclusions: Tumor response assessed using MRI after two cycles of NAT was highly correlated with pCR, and may be adopted as an optimal strategy for early evaluation of the efficacy of NAT regimen. Further studies are warranted to evaluate changes in treatment plan at early phase of NAT for those resistant to initial regimens.

Concordance between physician response assessment and a novel method per Lugano criteria in patients with lymphoma using real-world data.

e19082 Background: Clinical response assessment criteria, such as RECIST v1.1 and Lugano 2014, provide a standardized approach to assess treatment effectiveness in oncology clinical trials. Corresponding methodologies are needed for real-world data (RWD) to improve interpretability alongside clinical trial data and facilitate replication of results across RWD studies. We developed a RWD novel methodology, real-world Lugano (rwLugano), derived from Lugano 2014 criteria to classify lymphoma treatment response among patients with diffuse large B-cell lymphoma (DLBCL). Methods: A retrospective multisite RWD study identified adult patients with DLBCL treated with first line chemoimmunotherapy in US clinical practice (01JAN2015-31DEC2022). Participating sites abstracted clinical data via medical chart review and positron emission tomography-computed tomography (PET-CT) reports. Deidentified digital PET-CTs taken at treatment initiation and first response assessment were uploaded for BICR. Three distinct methods were used to assess treatment response: 1) physician-reported obtained from unstructured clinical notes in medical records, 2) rwLugano calculated using data (i.e., components of Lugano 2014) from PET-CT reports, and 3) BICR adjudication by two lymphoma radiologists using Lugano 2014 criteria. We compared the proportion of patients by response category: complete (CR), partial (PR), stable (SD) and progressive (PD) for each method. Analyses included agreement (%), concordance (Cohen’s kappa [κ]), and odds ratios with 95% confidence interval (OR; 95%CI) estimated using multivariable generalized linear mixed models (GLMM) adjusted for baseline characteristics. Results: The study identified 174 patients with DLBCL (female n=71 [41%]; white n=135 [78%]; Hispanic n=13 [7%]; mean age 66 years). Fewer patients were classified as CR at initial response via physician-reported response (n=111, 64%) compared to rwLugano (n=145, 83%), and BICR (n=142, 82%). Overall and CR agreement with BICR (see Table) was higher for rwLugano (overall: 83%, κ=0.49; CR: 86%, κ=0.50) than physician-charted response (overall: 72%, κ=0.45; CR: 76%, κ=0.43). In GLMM models, physician-charted response underestimated CR compared to BICR (OR=0.22, 95%CI:0.12-0.43), whereas rwLugano was statistically similar to BICR (OR=1.2, 95%CI:0.6-2.4). Conclusions: This study found that physician-reported response may underestimate CR at initial response, and rwLugano may be more consistent with BICR for treatment response assessment. Use of rwLugano warrants further evaluation as a methodology to assess treatment response in RWD lymphoma research. [Table: see text]

Outcomes of neoadjuvant chemotherapy and radical hysterectomy for locally advanced cervical cancer at Kigali University Teaching Hospital, Rwanda: a retrospective descriptive study

BackgroundHalf of countries in Africa lack access to radiation (RT), which is essential for standard treatment of locally advanced cervical cancers. We evaluated outcomes for patients treated with neoadjuvant chemotherapy (NACT) followed by radical hysterectomy in settings where no RT is available.MethodsWe performed a retrospective descriptive study of all patients with FIGO stage IB2-IIA2 and some exceptional stage IIB cases who received NACT and surgery at Kigali University Teaching Hospital in Rwanda. Patients were treated with NACT consisting of carboplatin and paclitaxel once every 3 weeks for 3–4 cycles before radical hysterectomy. We calculated recurrence rates and overall survival (OS) rate was determined by Kaplan-Meier estimates.ResultsBetween May 2016 and October 2018, 57 patients underwent NACT and 43 (75.4%) were candidates for radical hysterectomy after clinical response assessment. Among the 43 patients who received NACT and surgery, the median age was 56 years, 14% were HIV positive, and FIGO stage distribution was: IB2 (32.6%), IIA1 (7.0%), IIA2 (51.2%) and IIB (9.3%). Thirty-nine (96%) patients received 3 cycles and 4 (4%) received 4 cycles of NACT. Thirty-eight (88.4%) patients underwent radical hysterectomy as planned and 5 (11.6%) had surgery aborted due to grossly metastatic disease. Two patients were lost to follow up after surgery and excluded from survival analysis. For the remaining 41 patients with median follow-up time of 34.4 months, 32 (78%) were alive with no evidence of recurrence, and 8 (20%) were alive with recurrence. One patient died of an unrelated cancer. The 3-year OS rate for the 41 patients who underwent NACT and surgery was 80.8% with a recurrence rate of 20%.ConclusionsNeoadjuvant chemotherapy with radical hysterectomy is a feasible treatment option for locally advanced cervical cancer in settings with limited access to RT. With an increase in gynecologic oncologists skilled at radical surgery, this approach may be a more widely available alternative treatment option in countries without radiation facilities.

Abstract 4244: Clinical response assessment of immune checkpoint inhibitors in mismatch repair-deficient endometrial cancer using a T cell organoid coculture system

Abstract Endometrial cancers with the mismatch repair deficiency (MMR-D) phenotype exhibit characteristics such as an increased burden of tumor mutations and the presence of tumor-infiltrating lymphocytes (TILs) involved in tumor invasion. While monotherapy using immune checkpoint inhibitors (ICIs) has shown clinical improvement in MMR-D endometrial cancer (EC), observed response rates ranging from 30% to 50% suggest the existence of inherent resistance mechanisms. One notable feature of MMR-D tumors is the high proportion of tumor-infiltrating lymphocytes (TILs) encompassing various lymphocytes with diverse effects on immune interactions. Therefore, we aim to assess the feasibility of a self T-cell-tumor organoid co-culture platform for individual MMR-D endometrial cancer patients. We provide evidence that co-culturing self-tumor organoids with peripheral blood lymphocytes can be utilized to evaluate ICI responsiveness in MMR-D endometrial cancer patients. The application of a specific T-cell organoid co-culture platform to a cohort of patient resistant to monotherapy ICIs offers a means to anticipate the timing for minimal immunotherapeutic intervention and the appropriate timing for combination therapy. Citation Format: Ju Hee Oh, Eun Hye Choi, Ji Eun Lee, Eun Ji Nam. Clinical response assessment of immune checkpoint inhibitors in mismatch repair-deficient endometrial cancer using a T cell organoid coculture system [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 4244.

Laser Test Spots: A Scoping Review.

Laser test spots are commonly suggested for the assessment of clinical response and adverse effects, but use by laser operators is not well described. To describe the use of laser test spots in the existing published literature regarding methodology (location, treatment parameters) and objective (clinical efficacy, safety, other). This scoping review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines and included indexed studies performing test spots in human subjects for dermatologic conditions with clinical reassessment at a subsequent visit. Among 5,261 identified publications, 103 studies with 959 test spots were selected for inclusion. Test spots conducted were mostly on lesional skin (89.3%) assessing both clinical response and adverse effects (76.9%). Most test spots used multiple laser parameters with a single wavelength (48.3%). Fluence was most frequently adjusted either alone (30.1%) or in combination with pulse duration or spot size. Other described test spots examined single set of laser parameters, multiple wavelengths with various parameters, or were left unspecified. Laser test spot methodology was diverse and performed for dual objectives of efficacy and safety. The authors have compiled clinical considerations to assist laser operators in deciding whether performing a test spot may be beneficial to their patient.

Nursing diagnoses in patients undergoing prostatectomy at the central hospital of Nampula, 1st semester of 2019

Introduction: The nursing diagnosis is a clinical assessment of a human response to health conditions/life processes, or a vulnerability to that response, by an individual, family, group or community. The research aims to describe the main nursing diagnoses in patients undergoing prostatectomy admitted to Surgery II at the Hospital Central de Nampula. Objectives: This is a descriptive study with a quantitative approach, involving patients admitted to surgery II undergoing prostatectomy. All patients with the medical diagnosis of benign prostatic hyperplasia or prostate cancer who underwent prostate surgery were included, thus all patients who underwent prostate surgery but who had other chronic diseases were excluded. Data were analyzed with SPSS statistical package to obtain descriptive analysis, percentage and use of the following Q-square statistical test of independence. Results: the study involved 33 patients undergoing prostatectomy, 54.5% of these patients had primary schooling and the most predominant age group was 66-75 years old (39.4%). A total of 461 nursing diagnoses were found, and the most frequent were: Impaired walking 5.4%, Constipation 4.8, Risk of infection 6.9, Risk of vascular trauma 7.4%, Acute pain 5.4% and Deficit in self-care for bathing 6.7%. The following diagnoses were associated with the nursing diagnosis: impaired walking p value 0.000, dentition p value 0.006, constipation (p value 0.001), risk of electrolyte imbalance p value 0.000) and risk of falls (p value 0.000). Conclusion: the use of the nursing process by nurses facilitates the survey of health problems in sick patients in order to intervene in care using real nursing diagnoses, risk and health promotion.

P797 Assessment of pharmacokinetics and clinical response in patients transitioning from intravenous to subcutaneous vedolizumab

Abstract Background Vedolizumab is a humanized monoclonal antibody directed against α4β7 integrin used in inflammatory bowel disease (IBS) patients1. The usual dosage of Vedolizumab is 300 mg intravenously (iv). Recently the subcutaneous (sc) formulation (108 mg every 2 weeks) has been approved, which provides more independence for the patient, avoiding visits to the hospital and possible inconveniences associated with it2. Methods The aim of the study is to evaluate the clinical and biochemical response of IBS patients treated with vedolizumab, 16 weeks after transitioning from iv to sc. An observational, prospective, single-center cohort study was performed. Patients with IBS and maintenance treatment with vedolizumab, stable for at least 4 months, were offered to switch to sc formulation. At the same time of treatment administration a blood test was performed, with vedolizumab levels and fecal calprotectin. Clinical index as Harvey-Bradshaw Index (HBI)/Simple Clinical Colitis Activity Index (SCCAI) and questionaries (IBDQ-9 and TSQM) were performed on each visit. Results 43 patients were included, 12 of them (27.9%) chose to transition to sc formulation. Baseline characteristics of both groups are shown in Table 1. 34 (79.1%) patients were prescribed vedolizumab due to previous biologic failure, 7 (16.3%) in first line due to comorbidities and 2 (4.7%) because of adverse effects in prior treatment. All included patients remained in remission during follow-up. At week 16 (w16), no significant differences were found in calprotectin levels in patients on iv treatment (mean 146.6 ± SD 45.9) vs sc (159.26 ± 53.9) (p 0.9). Vedolizumab serum levels at w16 were higher in the sc group (22364.3 ± 5141.6) vs. iv (11425.9 ± 1514.2), with statistically significant differences (p 0.009). At w16, 9 (75%) of the patients in the SC group were highly satisfied with the medication and 11 (91.7%) considered it easy to administer. 1 patient (8.3%) in the sc group returned to iv treatment. 4 patients (12.9%) in iv and 2 (16.6%) in sc treatment presented mild adverse effects. The 2 cases (100%) of the sc group the adverse event was local inflammation at the injection site. Conclusion In our experience, vedolizumab sc is a safe and convenient alternative to iv administration. Vedolizumab serum levels in patients who transitioned to sc were higher than iv formulation. 1. Smith, Michael A et al. "Vedolizumab: an α4β7 integrin inhibitor for inflammatory bowel diseases." The Annals of pharmacotherapy vol. 48,12 (2014): 1629-35. 2. Vermeire, Séverine et al. "Efficacy and Safety of Subcutaneous Vedolizumab in Patients With Moderately to Severely Active Crohn's Disease: Results From the VISIBLE 2 Randomised Trial." Journal of Crohn's &amp; colitis vol. 16,1 (2022): 27-38.