Pathological Response Research Articles

Chemoradiotherapy and Subsequent Immunochemotherapy as Conversion Therapy in Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Phase II NEXUS-1 Trial.

This phase II trial investigated the safety and efficacy of chemoradiotherapy (CRT) followed by immunochemotherapy (iCT) and surgery in unresectable locally advanced esophageal squamous cell carcinoma (ESCC). Patients with unresectable locally advanced ESCC received radiotherapy (50 Gy/25f, 5 days/week) and nab-paclitaxel (100 mg on day 1/week) plus cisplatin (25 mg/m2 on day 1/week) for 5 weeks, followed by tislelizumab (200 mg on day 1/cycle) plus chemotherapy (nab-paclitaxel 150 mg/m2 and cisplatin 75 mg/m2 on day 2/cycle) for two 21-day cycles. Patients who converted to resectable underwent surgery 2 to 4 weeks afterward. The primary endpoint was a 1-year progression-free survival (PFS) rate. Thirty patients were enrolled and underwent CRT (median follow-up: 21 months), of whom 24 received iCT. Twenty (66.7%) patients achieved resectability (R0: 95.2%; pathologic complete response: 65.0%; major pathologic response: 90.0%). One-year PFS and overall survival (OS) rates were 79.4% and 89.6%, respectively. The R0 resection group exhibited longer PFS (median, not reached vs. 8.4 months; HR = 0.28; 95% confidence interval, 0.08-0.84; P = 0.02) and OS (median, not reached vs. 19.2 months; HR = 0.18; 95% confidence interval, 0.04-0.73; P < 0.01) than the nonsurgery group. Grade 3 to 4 adverse events were observed in 11 (11/30, 36.7%) patients, and immune-related pneumonitis was observed in 5 (5/24, 20.8%) patients. Post-CRT minimal residual disease before surgery was associated with unfavorable PFS and OS. Our study met the primary endpoint. Conversion CRT and subsequent iCT followed by surgery was a promising treatment strategy for unresectable locally advanced ESCC.

Multimodality deep learning radiomics predicts pathological response after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma.

This study aimed to develop and validate a deep-learning radiomics model using CT, T2, and DWI images for predicting pathological complete response (pCR) in patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant chemoradiotherapy (nCRT). Patients with ESCC undergoing nCRT followed by surgery were retrospectively enrolled from three institutions and divided into training and testing cohorts. Both traditional and deep-learning radiomics features were extracted from pre-treatment CT, T2, and DWI. Multiple radiomics models were developed, both single modality and integrated, using machine learning algorithms. The models' performance was assessed using receiver operating characteristic curve analysis, with the area under the curve (AUC) as a primary metric, alongside sensitivity and specificity from the cut-off analysis. The study involved 151 patients, among whom 63 achieved pCR. The training cohort consisted of 89 patients from Institution 1 (median age 62, 73 males) and the testing cohort included 52 patients from Institution 2 (median age 62, 41 males), and 10 in a clinical trial from Institution 3 (median age 69, 9 males). The integrated model, combining traditional and deep learning radiomics features from CT, T2, and DWI, demonstrated the best performance with an AUC of 0.868 (95% CI: 0.766-0.959), sensitivity of 88% (95% CI: 73.9-100), and specificity of 78.4% (95% CI: 63.6-90.2) in the testing cohort. This model outperformed single-modality models and the clinical model. A multimodality deep learning radiomics model, utilizing CT, T2, and DWI images, was developed and validated for accurately predicting pCR of ESCC following nCRT. Our research demonstrates the satisfactory predictive value of multimodality deep learning radiomics for the response of nCRT in ESCC and provides a potentially helpful tool for personalized treatment including organ preservation strategy. After neoadjuvant chemoradiotherapy, patients with ESCC have pCR rates of about 40%. The multimodality deep learning radiomics model, could predict pCR after nCRT with high accuracy. The multimodality radiomics can be helpful in personalized treatment of esophageal cancer.

The microbiota-gut-brain axis: a potential target in the small-molecule compounds and gene therapeutic strategies for Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by motor symptoms and non-motor symptoms. It has been found that intestinal issues usually precede motor symptoms. Microorganisms in the gastrointestinal tract can affect central nervous system through the microbiota-gut-brain axis. Accumulating evidence has shown that disturbances in the microbiota-gut-brain axis are linked with PD. Thus, this pathway appears to be a promising therapeutic target for treatment of PD. In this review, we mainly described gut dysbiosis in PD and their underlying mechanisms for mediating neuroinflammation and peripheral immune response in PD pathology and futher discussed the potential small-molecule compounds and genic therapeutic strategies targeting the microbiota-gut-brain axis and their applications in PD. Studies have found that some small molecule compounds and alterations of inflammation-related genes can improve the motor and non-motor symptoms of PD by improving the microbiota-gut-brain axis, which may provide potentially beneficial drugs and molecular targets for the therapies of PD.

Pathologic complete response to conversion therapy in hepatocellular carcinoma using patient-derived organoids: A case report

Pathologic complete response to conversion therapy in hepatocellular carcinoma using patient-derived organoids: A case report

Sympathetic nerve activity and response to physiological stress in Takotsubo syndrome.

The prevailing hypothesis posits that Takotsubo syndrome (TTS) is caused by massive sympathetic activation, yet supporting evidence remains inconsistent. The objectives of the present study were to determine whether sympathetic activity and reactivity are enhanced in the recovery phase of TTS, and to evaluate the effect of selective β1-receptor blockade on sympathetic reactivity. We conducted a case-control study that included 18 female patients with TTS and 13 age- and sex-matched controls. Muscle sympathetic nerve activity was measured through microneurography of the peroneal nerve at rest and during the cold pressor test. In the TTS group, recordings were repeated after randomisation to intravenous metoprolol or placebo. In 10 TTS patients, cardiac sympathetic activity was assessed using iodine123-metaiodobenzylguanidine scintigraphy. Blood samples were collected during hospitalisation. Microneurography was performed a median of 27.5days after patient admission. There were no significant differences in burst incidence, burst frequency, burst height or burst area between the TTS patients and the controls at rest, during stress or after administration of intravenous metoprolol. Iodine123-metaiodobenzylguanidine scintigraphy was performed a median of 12.5days after admission, revealing decreased early 1.54 ± 0.13 and late 1.40 ± 0.13 heart-to-mediastinum ratios, and an increased washout rate of 41.8 ± 12.1%. Catecholamine metabolites were comparable between the study groups. General sympathetic hyperactivity or hyperreactivityunlikelycontributesto TTS, as catecholamine levels and muscle sympathetic nerve activity at rest and during stress were similar between the TTS patients and the controls.As scintigraphy showed increased cardiac sympathetic activity, a pathological cardiac adrenergic response and vulnerability to sympathetic activationmay be crucial for the development of the syndrome.

ASO Visual Abstract: Prediction of Pathologic Complete Response in Esophageal Squamous Cell Carcinoma Using Preoperative Serum Small Ribonucleic Acid Obtained After Neoadjuvant Chemoradiotherapy.

ASO Visual Abstract: Prediction of Pathologic Complete Response in Esophageal Squamous Cell Carcinoma Using Preoperative Serum Small Ribonucleic Acid Obtained After Neoadjuvant Chemoradiotherapy.

Racial/ethnic differences in survival and treatment response with PD-1/PD-L1 inhibitors in resectable non-small cell lung cancer: a meta-analysis of randomized controlled trials.

The optimal treatment for resectable Non-Small Cell Lung Cancer (NSCLC) remains under investigation, particularly about its effectiveness across different ethnicities. This meta-analysis aims to investigate the potential benefits of adding PD1/PD-L1 inhibitors for treatment, stratified by ethnicity. We searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) that investigated the use of PD1/PD-L1 inhibitors to treat patients with resectable NSCLC. The outcomes evaluated were disease-free survival/event-free survival (DFS/EFS), major pathological response (MPR), and pathological complete response (pCR). Hazard ratios (HRs) or risk ratios (RRs) with 95% confidence intervals (CIs) were computed for all endpoints using DerSimonian and Laird random-effects models. Statistical analyses were performed with R Software, version 4.2.3. A total of six RCTs comprising 3,827 patients with NSCLC were included. In populations of Asian descent, PD1/PD-L1 significantly improved DFS/EFS (HR 0.59; 95% CI 0.44-0.78), MPR (RR 5.76; 95% CI 3.58-9.28), and pCR (RR 25.00; 95% CI 6.17-101.36). Similarly, patients of European ancestry experienced significantly improved DFS/EFS (HR 0.77; 95% CI 0.65-0.90), MPR (RR 2.75; 95% CI 2.00-3.77), and pCR (RR 4.53; 95% CI 2.69-7.6) with PD1/PD-L1 therapy. Notably, patients with mixed ethnicity also demonstrated significant improvement in MPR (RR 4.05; 95% CI 2.60-6.33) and pCR (RR 8.44; 95% CI 3.75-19.00) when receiving PD1/PD-L1 inhibitors. This comprehensive meta-analysis suggests that incorporating PD1/PD-L1 inhibitors into treatments offers a promising benefit for patients with resectable NSCLC, regardless of ethnicity. Future studies with in-depth molecular characterization of patients can further refine these findings and potentially guide the development of personalized treatment strategies based on individual ethnic backgrounds.

Systemic chemokine-modulatory regimen combined with neoadjuvant chemotherapy in patients with triple-negative breast cancer

BackgroundHigher cytotoxic T lymphocyte (CTL) numbers in the tumor microenvironment (TME) predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) and positive long-term outcomes in triple-negative breast cancer (TNBC). pCR...

Immune checkpoint inhibitor therapy as a neoadjuvant treatment for muscle-invasive bladder carcinoma

Abstract Background and objectives Immunotherapy has become a standard treatment for patients with advanced urothelial carcinoma, and neoadjuvant immunotherapy is being extensively explored. This review highlights the initial findings and key clinical therapeutic insights on immune checkpoint inhibitors in the early treatment of muscle-invasive bladder cancer across diverse patient populations. Materials and methods Relevant trials were retrieved from PubMed/MEDLINE and clinical trials databases. In addition, abstracts of major international oncology meetings (American Society of Clinical Oncology, American Association for Cancer Research, European Society of Medical Oncology, and European Council of Clinical Oncology) were reviewed until the European Society of Medical Oncology 2023 congress. The review also incorporated results from several exploratory investigations disclosed in recent years. Results This review focused on neoadjuvant immune checkpoint inhibitor monotherapy, combination therapy, and clinical biomarkers in relation to cisplatin-based chemotherapy tolerance. Most available literature consists of clinical investigations involving small sample, single-arm Phase II trials, with the primary endpoint being the pathologic complete response rate. The preliminary results from these studies are promising, demonstrating stage reduction rates comparable to or even exceeding those of standard chemotherapy, without compromising subsequent radical cystectomy. Conclusions Early results of immune checkpoint inhibitors in the neoadjuvant treatment of bladder cancer have demonstrated promising efficacy. However, these findings require confirmation in large Phase III clinical trials, with particular emphasis on long-term survival benefits and identifying patients who respond to treatment.

Protective effect of maltol on pathological response of cardiomyocyte in dystrophic mice.

Heart diseases are a significant contributor to global morbidity and mortality, and despite their diverse and complex mechanisms, treatment options remain limited. Maltol, a natural compound with antioxidant and anti-inflammatory activities, exhibits potential for addressing this need. This study evaluates the cardioprotective effects of maltol in isoproterenol (ISO)-induced cardiac stress models and Duchenne muscular dystrophy (DMD). Maltol's cardiac cytotoxicity was assessed in rodent (H9c2) and human (AC16) cells and compared with that of dapagliflozin to illustrate its cardiac safety. In ISO-induced stress models, maltol significantly reduced hypertrophic markers and inflammation while enhancing autophagy and antioxidant pathways. In the mdx mice, a DMD model, maltol treatment improved cardiac contractility and reduced pathogenic remodeling. Enhanced phosphorylation of phospholamban and trends toward higher SERCA2a expression indicated enhanced Ca2+ handling, which is crucial in DMD cardiomyopathy. This study demonstrated that maltol has the potential to provide therapeutic benefits for DMD and other cardiac conditions characterized by hypertrophy and inflammation, as evidenced by its well-known antioxidant properties, low cytotoxicity, and capacity to enhance cardiac function and Ca2+ handling.

Muscle spindle receptors and their impact on Parkinson´s disease and Cerebral Palsy subjects.

In some neurological conditions, like Parkinson's disease (PD) and Cerebral Palsy (CP), as well as with ageing, muscle spindles have been mentioned as participating in the pathological response of observed muscles. The aim of this review has therefore been to examine what is known about muscle spindle receptors, their function and how they are involved in regulating precise muscle movement in relation to these two conditions. Data from acoustic myography (AMG) studies with healthy controls (HC), CP and PD subjects have been re-examined with a view to identifying possible effects of changes in muscle movement which could be related to muscle spindle receptor function. Studies of muscle spindles have shown that during shortening and lengthening contractions the fusimotor system is activated differently with different discharge frequencies and sensitivities. With increasing age comes a loss of precise proprioception, something that coincides with a change in the AMG E-score towards lower values, indicating a reduced level of coordination and efficiency of muscle use. With PD and CP there is likewise a documented decrease in proprioception, also showing lower E-values than age-matched HC subjects. We conclude that the decrease in proprioception observed in these subjects must be partly due to a change in the muscle spindle / C-centre feedback system.

Transarterial Chemoembolization in Locally Advanced Rectal Cancer: A Systematic Review

Background: Locally advanced rectal cancer (LARC) presents a significant treatment challenge. Transarterial chemoembolization (TACE) has emerged as a potential adjunctive treatment, offering targeted delivery of chemotherapeutic agents to the tumor site, minimizing systemic exposure. This systematic review aims to assess the current literature on this novel technique and evaluate the safety and efficacy profile of TACE in treating this complex cohort of patients. Methods: A comprehensive literature search was conducted across multiple databases, including PubMed, EMBASE, and Cochrane Library, to identify studies evaluating TACE in LARC. Inclusion criteria encompassed clinical trials, cohort studies, and case series reporting on outcomes such as tumor response rate, overall survival (OS), progression-free survival (PFS), and treatment-related adverse events. Results: A total of eight studies involving 543 patients met the inclusion criteria. The studies varied in design, with five prospective and three retrospective studies. A higher prevalence of male participants (68.7%) was noted, with a median age of 60.3 years. The studies primarily evaluated the efficacy and safety of TACE in LARC treatment. Pathological response rates, tumor reduction, and survival outcomes varied across studies, with TACE showing promise in reducing tumor size, improving survival, and controlling metastasis. Major complications were rare, reported in 6.0% of cases. Conclusions: TACE is a promising therapeutic option for patients with LARC, demonstrating favorable tumor response rates and manageable toxicity profiles. Further large-scale, randomized controlled trials are warranted to confirm these findings and better define the role of TACE in the multimodal treatment of LARC.

OGC O05 - Utilising patient derived organoids to predict the response to treatment in gastric cancer

Abstract Background Gastric adenocarcinoma remains a significant global health burden. For advanced disease, treatment remains multi-modal with neoadjuvant chemotherapy followed by resectional surgery. Although the FLOT4-AIO trial has established the regimen of 5-fluorauracil, Leucovorin, Oxaliplatin and Docetaxel (FLOT) as the gold standard, some patients demonstrate a poor or no response to treatment, resulting in adverse oncological outcomes. Currently there are no accurate biomarkers to assess or predict the treatment response to neoadjuvant therapy. This study aims to explore the potential of patient-derived organoids as a predictive model to assess the treatment response to neoadjuvant chemotherapy in gastric adenocarcinoma. Method Patient derived organoids are a novel, 3 dimensional in-vitro model which recapitulates the different cells that constitute the tissue of origin. From June 2023 to June 2024, 25 patients with a confirmed diagnosis of gastric adenocarcinoma, were recruited for tissue acquisition for organoid generation. Endoscopic biopsies of cancer tissue taken during OGD and staging laparoscopy were used to generate organoids from each patient. Organoids were subsequently expanded to a sufficient volume to allow cytotoxicity assays in response to different doses of the FLOT regimen. The organoid cytotoxicity response was compared to the patients radiological and pathological response following treatment. Results Organoids were successfully generated from 76% of recruited patients (n=19). Of these, 4 patients and were excluded due to being unfit for neoadjuvant chemotherapy, whilst 2 were excluded due to the confirmation of metastatic disease, precluding neoadjuvant treatment. Finally a single patient was excluded due to mortality during neoadjuvant treatment. Of the remaining organoids, 5 were subjected to FLOT treatment within 2 weeks of tissue acquisition. Organoids demonstrated unique dose response profiles following with statistically significant differences in the IC50 values (p =0.048). The organoid responses corresponded to the clinical responses demonstrated by the patient they were derived from. Conclusion In conclusion, this study underscores the potential of patient-derived cancer organoids as a predictive model for assessing the response to neoadjuvant chemotherapy in gastric adenocarcinoma. The generation of organoids from a significant proportion of patients and the subsequent drug response testing within 2 weeks of tissue acquisition suggests this novel method has the potential to become a valuable tool for predicting patient-specific responses and guiding personalised treatment plans. As such, further research is warranted to further assess the validity of this model, refine the existing techniques and explore its potential integration into clinical practice.

SOX combined with tislelizumab and low-dose radiation therapy for the neoadjuvant treatment of locally advanced gastric/gastroesophageal junction adenocarcinoma: study protocol for a prospective, multicenter, single-arm, phase Ib/II clinical trial

BackgroundRecently, the clinical benefits of neoadjuvant chemotherapy combined with immunotherapy have been observed in patients with locally advanced gastric or gastroesophageal junction (G/GEJ) cancer; however, the pathological complete response (pCR) and long-term survival rates are still unsatisfactory. The aim of this study is to investigate the efficacy and safety of chemotherapy combined with tislelizumab and low-dose radiation therapy (LDRT) for the neoadjuvant treatment of locally advanced G/GEJ cancer.MethodsThis is a prospective, multicenter, single-arm, phase Ib/II trial. In the phase Ib study, 5 patients will be enrolled in each treatment group with different radiation doses. In the phase II study, a total of 44 patients will be enrolled. Eligible patients will be registered and receive three cycles of SOX regimen chemotherapy (S-1: 40-60 mg Bid, d1-14, q3w; oxaliplatin: 130 mg/m2, iv drip, d1, q3w) plus tislelizumab (200 mg, iv drip, d1, q3w). Simultaneously, LDRT will be planned and administered after the first cycle of systemic therapy. Radical D2 gastrectomy will be performed 4-6 weeks after the last administration of chemotherapy plus tislelizumab. The primary endpoint of phase Ib study is to determine the optimal radiation dose for phase II study. The primary endpoint of phase II is the pCR rate. The secondary endpoints include R0 resection rate, major pathological response (MPR) rate, 2-year event-free survival (EFS) rate, 2-year overall survival (OS) rate and safety profile. Moreover, we will also explore potential molecular markers for predicting the benefit and safety of this neoadjuvant regimen. Written informed consent should be provided by all patients enrolled in the study. The study protocol was approved by the independent ethics committee at each institution.DiscussionThis is the first study to explore the efficacy and safety of neoadjuvant chemotherapy combined with tislelizumab and LDRT in G/GEJ cancer patients, the results of which may provide novel treatment strategy for patients with locally advanced G/GEJ adenocarcinoma.Clinical trial registrationClinicalTrials.Gov, identifier NCT06266871.

Abstract B008: Evaluating ctDNA as a risk-stratifying biomarker in non-metastatic triple-negative breast cancer treated with neoadjuvant chemotherapy

Abstract Introduction: Patients with triple-negative breast cancer (TNBC) who respond well to neoadjuvant chemotherapy (NACT) generally experience favorable outcomes. However, those with residual disease after NACT face a higher risk of relapse and exhibit varying outcomes. Therefore, additional tools for assessing relapse risk are critical for guiding personalized treatment strategies. We aim to investigate the role of circulating tumor DNA (ctDNA) in conjunction with homologous recombination deficiency (HRD) as a risk-stratifying biomarker in TNBC patients with residual disease. Methods: TNBC were classified as HRD-Hereditary or Sporadic using multi-gene genetic testing. Comprehensive Genomic Profiling (CGP) was performed and tumor acquired small variants were tracked in plasma samples by a personalized-amplicontarget-sequencing (PATS) approach. Plasma samples were collected at six key time points: before treatment (BT), after the first block of NACT (ab1Neo), post-completion of NACT (aNeo), after tumor resection (aSur), and at two monitoring intervals every three months (M3m and M6m). Results: Of 105 TNBC patients tested for germline variants, 26% were classified as HRD-Hereditary, primarily due to BRCA1 mutations. CGP was performed on 73 tumors, with 12.5% displaying high tumor mutation burden (TMB), not associated with HRD- Hereditary status. Tumor-specific variants were identified in 95% (69/73) of cases, with TP53 variants being the most frequent (84%). Regarding response to NACT, 55% (58/105) achieved pathological complete response (RCB=0), while 11% (12/105) had RCB=I, 16% (17/105) RCB=II, 10% (11/105) RCB=III and 7% (7/105) unavailable RCB score. ctDNA analysis was feasible for 62% (65/105) of cases. Positive ctDNA (ctDNApos) was detected in 66.2% (43/65) at BT, 48.4% (30/62) at ab1Neo, 25.4% (15/59) at aNeo, 32.8% (20/61) at aSur, 18.6% (11/59) at M3m and 28.6% (14/49) at M6m. Interestingly, sporadic tumor patients exhibited significantly higher ctDNApos rates compared with HRD-Hereditary tumors at BT, aNeo, and aSur. No significant association was found between ctDNApos at any timepoint and RCB scores. Strong negative predictive value of RCB=0/1 and ctDNAneg aSur for progression was observed (94.2% - 65/69 and 85.4% - 35/41, respectively; mean follow-up 39.7 months, median 36.9 months). In contrast, the positive predictive value for both RCB=2/3 and ctDNApos aSur was relatively low (50% - 14/28; 50% - 10/20, respectively). However, when ctDNApos at aSur were combined with RCB=2/3, the PPV improved to 77.8%. Moreover, ctDNApos was significantly associated with clinical progression at BT (p=0.0359) and aSur (p=0.0053) and consistently anticipated progression detected by standard imaging, with a mean lead-time of 4.7 months. Patients with ctDNApos also demonstrated worse progression-free survival, strongly suggesting its potential as a prognostic marker. Conclusions: ctDNA appears to be a promising risk-stratifying biomarker for TNBC patients with residual cancer, offering valuable insights for tailoring patient management and improving outcomes. Citation Format: Rafael Canfield Brianese, Karina Miranda Santiago, Nathalia de Angelis de Carvalho, Marina de Brot Andrade, Giovana Tardin Torrezan, Vladmir Claudio Cordeiro de Lima, Solange Moraes Sanches, Maria Nirvana da Cruz Formiga, Fabiana Baroni Alves Makdissi, Dirce Maria Carraro. Evaluating ctDNA as a risk-stratifying biomarker in non-metastatic triple-negative breast cancer treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B008.

OGC SO42 - A comparison of body composition changes between neoadjuvant FLOT and MAGIC regimes in patients with locally advanced oesophageal cancer

Abstract Background Several studies have documented the changes in body composition that can occur between pre and post neoadjuvant chemotherapy for locally advanced OGA. However, none have compared the changes between different neoadjuvant regimes following the shift in practice from MAGIC to FLOT neoadjuvant chemotherapy. Specifically, given that the FLOT regimen has been thought to be more toxic than MAGIC regimen, it is unclear whether this toxicity is measurable and clinically significant with regards to body composition. This study aims to compare the changes in body composition between these two regimens in patients with locally advanced oesophageal cancer. Method We conducted a retrospective cohort study comparing changes in body composition between patients receiving either MAGIC or FLOT neoadjuvant chemotherapy. 115 patients treated with FLOT (n = 61) or MAGIC (n = 54) who underwent an oesophagectomy for OGA between 2008 and 2020 at Queen Elizabeth Hospital, Birmingham, UK were ultimately enrolled in the study. Changes in body composition between pre- and post-neo-adjuvant chemotherapy were determined by analysis of computed tomography (CT) imaging. Slice-O-Matic is a software tool allowing segmentation of body tissues into different classes Including skeletal muscle and fat based on the Hounsfield units. Results Our findings showed a statistically significant difference in the weight loss of participants enrolled the MAGIC group compared to FLOT (FLOT -0.6 ±6.9 vs MAGIC -3.4 ±1.2, p=0.034) which was therefore also reflected in BMI differential before and after neoadjuvant chemotherapy (FLOT -0.2 ± 2.2 vs MAGIC -1.2 ± 2.7, p=0.024). However, there was no statistically significant difference in the L3 skeletal muscle index in both regimes (FLOT -2.8 ± 4.1 vs MAGIC -2.9 ± 4.1; p=0.93). Finally, changes in L3 fat index between the two cohorts did not demonstrate statistically significant difference in our study (FLOT -0.9 ± 22.6 vs MAGIC -5.6 ± 24.8; p=0.29). Conclusion Our study suggests that a large proportion of patients with locally-advanced OGA were sarcopenic prior to starting chemotherapy and this proportion increased post treatment. There was no statistically significant loss of muscle mass or fat during treatment with either MAGIC or FLOT. Despite this, weight loss and decreases in BMI were greater in the MAGIC group compared to FLOT, suggesting FLOT may have a more favourable toxicity profile with regard to body composition. Overall, our findings support the safety profile of FLOT chemotherapy with regard to body composition changes and illustrates a superior pathological response to FLOT therapy for OGA.

Association between mammographic breast density and outcome in patients with unilateral invasive breast cancer receiving neoadjuvant chemotherapy.

To analyze the relationship between mammographic breast density and tumor response and outcome at follow-up, in terms of overall survival (OS) and disease-free survival (DFS), in patients with unilateral invasive breast cancer receiving neoadjuvant chemotherapy (NACT). A total of 228 women (mean age, 47.6years ± 10 [SD]; range: 24-74years) with invasive breast cancer who underwent NACT were included in this observational retrospective study. Clinical, radiological and histopatological data were retrieved. Categorization of breast density was performed by two radiologists in consensus on mammography acquired at the time of diagnosis according to BI-RADS categories. Association between density categories and tumor response was analyzed in the overall population and in subgroups defined by menopausal status, tumor phenotype and stage at diagnosis. Kaplan-Meier (KM) curves were used to estimate the OS and DFS probabilities. Subgroup analyses based on menopausal status and tumor phenotype were performed. A total of 30 patients (13.2%) achieved pathological complete response (pCR). No association between density categories and pCR was found (P = 0.973), even at subgroups analysis. The median follow-up time was 92months. Patients with dense breast showed the longest DFS (P = 0.0094), results confirmed in premenopausal patients (P = 0.0024) and in triple negative breast cancers (P = 0.0292). Density category did not show a statistically significant association with OS. Breast cancer patients receiving NACT with extremely dense breasts showed better DFS. No evidence of breast density as a predictive marker for complete pathological response or as a prognostic factor in terms of OS was found.

Abstract 4133460: VCAM1 contributes to pathogenesis during influenza-induced exacerbation of atherosclerosis.

Background and hypothesis: Influenza is a significant public health and economic threat around the world. Although pneumonia is the most common complication associated with influenza, there are several clinical reports demonstrating increased risk for cardiovascular disease. Influenza infection induces interferons, proinflammatory cytokines and chemokines, and recruits’ macrophages and neutrophils to control the virus. However, an excessive influx of innate immune cells and dysregulated production of inflammatory mediators results in pathological responses during influenza infection. Studies have shown that influenza infection correlates with increased incidence of myocardial infarction. Atherosclerosis is the most known cause of ischemic heart diseases and stroke. Vascular cell adhesion molecule-1 (VCAM1) has been shown to promote adhesion of monocytes and promotes atherosclerosis. In this study, we hypothesize that VCAM1 plays a role in exacerbation of atherosclerosis during influenza infection. Methods: High-Fat diet (HFD)-fed Apoe -/- mice were infected with influenza A/PR/8/34 (H1N1) and weight loss, survival rate, and gene expression of vascular endothelial adhesion molecules, inflammatory cytokines and chemokines were measured. HFD-fed Apoe -/- mice were infected with influenza, and treated with anti-VCAM1 antibody, and weight loss and cellular responses were measured. Results and conclusions: Increased weight loss and decreased survival of mice were observed in response to influenza infection in HFD-induced atherosclerosis in Apoe -/- mice. Further, the expression of VCAM1, and the levels of IL-6, CCL2, CCL3, CCL5 were significantly increased in aorta in Apoe -/- mice when compared to PBS-treated controls. Increased survival, decreased weight loss, decreased lesion area, decreased frequency of CD11b + F4/80 + Ly6C + , CD4 + RORgt + cells and increased frequency of CD4 + FoxP3 + Treg cells were observed in aorta in response to antibody mediated VCAM1 neutralization. These results suggest that VCAM1 plays a pathological role in influenza-induced exacerbation of atherosclerosis.

Evaluation of Volumetric Magnetic Resonance Imaging in Determining the Indication for Total Neoadjuvant Therapy in Rectal Cancer.

This study aims to evaluate the relationship between volumetric measurements of residual tumor via magnetic resonance imaging (MRI) and pathologic complete response (pCR) in rectal cancer patients undergoing neoadjuvant chemoradiotherapy (nCRT). Patients with locally advanced rectal cancer who had pelvic MRI for clinical staging and completed nCRT followed by radical resection were included. Two experienced radiologists measured tumor volume on MRI obtained before and after nCRT. We compared the pre- and post-CRT tumor volume and measured tumor volume reduction rates. The median value of tumor volume reduction rate in all patients was 64.7% (min-max - 81.1-98.1%). When the relationship between tumor volume and tumor regression grade (TRG) after nCRT was assessed, it was found that 18 of 21 (86%) patients with a good response (TRG 1) had a post-CRT tumor volume of ≤ 8 cm3 (p = 0.001). While 9 of 10 patients with pCR after nCRT had a tumor volume of ≤ 8 cm3, one patient had pCR despite having a tumor volume greater than 8 cm3 (p = 0.015). The correlation between post-nCRT residual tumor volume and pCR underscores the potential of volumetric MRI as a predictive tool in tailoring rectal cancer treatment. For patients with residual tumor volumes greater than 8 cm3, extending neoadjuvant chemotherapy as part of TNT may enhance the likelihood of achieving pCR. This approach advocates for a more personalized treatment strategy, potentially optimizing outcomes for rectal cancer patients.

Target-Engineered Liposomes Decorated with Nanozymes Alleviate Liver Fibrosis by Remodeling the Liver Microenvironment.

Liver fibrosis is a pathological repair response that occurs after sustained liver damage, and prompt intervention is necessary to prevent liver fibrosis from developing into a potentially life-threatening condition. In long-term liver injury, damaged hepatocytes produce excessive amounts of reactive oxygen species (ROS), which activate hepatic stellate cells (HSCs). This activation leads to excessive accumulation of extracellular matrix proteins in liver tissue. Additionally, liver macrophages contribute to the inflammatory microenvironment in the hepatic fibrotic process, exacerbating liver fibrosis through ROS production and the secretion of pro-inflammatory factors. To address the dysregulation of the hepatic microenvironment associated with liver fibrosis, we developed cerium oxide nanozymes using hyaluronic acid (HA) as a template and decorated them on the surface of liposomes loaded with oleanolic acid (OA). We named this prepared and obtained target-engineered liposome HCOL. The inherent superoxide dismutase (SOD) and catalase (CAT) activities of HCOL enabled it to effectively scavenge ROS in HSCs and alleviate the hypoxic conditions characteristic of fibrotic livers. Furthermore, HCOL reduced the concentrations of ROS in macrophages, promoting a shift in macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. This transition increased the production of the anti-inflammatory cytokine interleukin 10 (IL-10), which contributed to the mitigation of the inflammatory microenvironment. Consequently, this therapeutic approach proves effective in decelerating the advancement of liver fibrosis.