Adjuvant Treatment Strategies Research Articles

Pattern of LRR in Endometrial Cancer and Identification of Predictive Factors

Background: Tailored adjuvant treatment is key to managing endometrial cancer effectively. Understanding prognostic factors of loco-regional failure and the impact of adjuvant treatment can help in treatment de-escalation without compromising survival outcomes. The aim of this study was to assess the pattern of failure in endometrial cancer patients and to determine predicting Loco-Regional Recurrence (LRR) factors. Patients and methods: Data were collected from 214 patients treated for endometrial cancer between 2005 and 2012 in Salah Azaiez Institute in Tunisia. All patients underwent upfront surgery followed by adjuvant brachytherapy with or without external beam radiation. The median follow-up period was 44 months. Univariate and multivariate analyses were performed to identify prognostic factors for LRR. Results: The 5-year overall survival rate was 78.1%, and the 5-year progression-free survival rate was 80.1%. LRR occurred in 25 patients (11.6%), with a median recurrence time of 29 months (range 4 months - 46 months). Pelvic relapse was the most common site, occurring in 10 patients. Vaginal relapses were observed in 9 patients, and retro-peritoneal relapses were observed in 6 cases. FIGO stage, tumor grade, histologic type, Lympho-Vascular Space Invasion (LVSI), and delays in adjuvant treatment were significant predictors of LRR. Conclusion: Identifying prognostic factors for LRR in endometrial cancer is crucial for optimizing adjuvant treatment strategies. Higher FIGO stages and the presence of LVSI were independent predictive factors for LRR. Tailored adjuvant treatment, taking these prognostic factors into account, is essential to improve patient outcomes and minimize unnecessary treatment-related toxicity.

Predicting Regional Recurrence and Prognosis in Stereotactic Body Radiation Therapy-Treated Clinical Stage I Non-small Cell Lung Cancer Using a Radiomics Model Constructed With Surgical Data

BackgroundRisk stratification of regional recurrence (RR) is clinically important in the design of adjuvant treatment and surveillance strategies in patients with clinical stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). PurposeTo develop a radiomics model predicting occult lymph node metastasis (OLNM) using surgical data and apply it to the prediction of RR in SBRT-treated early-stage NSCLC patients. MethodsPatients with clinical stage I NSCLC who underwent curative surgery with systematic lymph node dissection from January 2013 to December 2018 (the training cohort) and from January 2019 to December 2020 (the validation cohort) were included. A pre-operative CT-based radiomics model, a clinical feature model, and a fusion model predicting OLNM were constructed. The performance of the three models was quantified and compared in the training and validation cohorts. Subsequently, the radiomics model was used to predict RR in a cohort of consecutive SBRT-treated early-stage NSCLC patients from two academic medical centers. ResultsA total of 769 patients were included. Eight CT features were identified in the radiomics model, achieving areas under the curves (AUCs) of 0.85 (95% CI 0.81-0.89) and 0.83 (95% CI 0.80-0.88) in the training and validation cohorts, respectively. Nevertheless, adding clinical features did not improve the performance of the radiomics model. With a median follow-up of 40.0 (95% CI 35.2-44.8) months, 32 of the 213 patients in the SBRT cohort developed RR and those in the high-risk group based on the radiomics model had a higher cumulative incidence of RR (p<0.001) and shorter regional recurrence-free survival (p=0.02), progression-free survival (p=0.004) and overall survival (p=0.006) than those in the low-risk group. ConclusionThe radiomics model based on pathologically confirmed data effectively identified patients with ONLM, which may be useful in the risk stratification among SBRT-treated patients with clinical stage I NSCLC.

The Evolving Role of Genomic Testing in Early Breast Cancer: Implications for Diagnosis, Prognosis, and Therapy.

Multigene prognostic genomic assays have become indispensable in managing early breast cancer (EBC), offering crucial information for risk stratification and guiding adjuvant treatment strategies in conjunction with traditional clinicopathological parameters. The American Society of Clinical Oncology (ASCO) guidelines endorse these assays, though some clinical contexts still lack definitive recommendations. The dynamic landscape of EBC management demands further refinement and optimization of genomic assays to streamline their incorporation into clinical practice. The breast cancer community is poised at the brink of transformative advances in enhancing the clinical utility of genomic assays, aiming to significantly improve the precision and effectiveness of both diagnosis and treatment for women with EBC. This article methodically examines the testing methodologies, clinical validity and utility, costs, diagnostic frameworks, and methodologies of the established genomic tests, including the Oncotype Dx Breast Recurrence Score®, MammaPrint, Prosigna®, EndoPredict®, and Breast Cancer Index (BCI). Among these tests, Prosigna and EndoPredict® have at present been validated only on a prognostic level, while Oncotype Dx, MammaPrint, and BCI hold both a prognostic and predictive role. Oncologists and pathologists engaged in the management of EBC will find in this review a thorough comparison of available genomic assays, as well as strategies to optimize the utilization of the information derived from them.

Adjuvant treatment strategy evolution and risk stratification for hormone receptor-positive, human epidermal growth factor receptor-2 negative early breast cancer in China.

Patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) early breast cancer (EBC) with high-risk clinicopathological features face an increased risk of recurrence. This study explored the evolving treatment landscape and clinical outcomes in patients with EBC using a nationwide database. The study cohort comprised HR+/HER2-, stages 1-3, patients with EBC who underwent surgery and received adjuvant endocrine therapy (AET) from January 2013 to March 2021. High-risk patients were defined by ≥4 positive axillary lymph nodes, or 1-3 positive lymph node(s) with at least one high-risk feature (histologic grade 3, tumor size ≥5cm, or Ki-67 ≥20%). A low-risk cohort included patients not meeting the criteria. Survival analysis was conducted with a cutoff of September 2021. The study included 4088 eligible patients (1310 high-risk patients and 2778 low-risk patients). High-risk patients were more likely to receive adjuvant chemotherapy and radiotherapy compared to low-risk patients. From 2013 to 2021, an increasing proportion of patients received aromatase inhibitors and ovarian function suppression as part of their AET. The 2-, 5-, and 7-year invasive disease-free survival for high-risk cohort were 90.67%, 75.26%, and 57.10%, respectively, these rates were notably higher for low-risk cohort at 97.14%, 89.85%, and 84.83%. High-risk patients demonstrated a higher risk of recurrence or death compared with low-risk patients (hazard ratio, 2.38; 95% CI, 1.82-3.12). In the setting of standard or even intensive AET, patients with EBC with high-risk features still present high recurrence risk, highlighting the urgent need for innovative adjuvant treatment strategies.

Cobalt-containing calcium silicate nanowires incorporated scaffolds for the repair of osteochondral defect induced by chondrosarcoma

Considering the difficulty in the treatment of chondrosarcoma in clinic, multifunctional composite hydrogel scaffolds were designed with excellent photothermal ability for the regeneration of damaged bone and cartilage tissue. The chitosan solution/polyvinyl alcohol (CP) hydrogels with different contents of cobalt doped calcium silicate (Co-CSH) nanowires were prepared via 3D printing method. Attributing to the excellent photothermal performance of Co-CSH nanowires, the average survival rate of human chondrosarcoma cells in the CP-5Co-13.4 % and CP-5Co-16.2 % scaffolds with near infrared laser irradiation was about 10.5 % and 9.9 %, respectively. At the same time, the prepared composite hydrogel scaffolds possessed satisfactory biocompatibility and could support the adhesion and spread of rabbit bone mesenchymal stem cells (rBMSCs) and rabbit chondrocytes in the hydrogel scaffolds, and further promoted the formation of new bone and cartilage tissue in vivo, on account of the stimulation effect of released bioactive ions. Therefore, the prepared composite hydrogel scaffolds is expected to provide a new therapeutic strategy for the postoperative adjuvant treatment of chondrosarcoma.

Abstract PO4-15-12: Personalized circulating tumor DNA monitoring to predict response to neoadjuvant therapy in patients with early-stage breast cancer

Abstract Introduction Longitudinal ctDNA testing offers a minimally invasive approach for monitoring treatment response in patients with breast cancer (BC). In this study, we evaluated whether serial ctDNA testing during neoadjuvant therapy (NAT) can provide an early indication of treatment response or resistance and disease progression. Methods In this real world study, longitudinal blood samples collected from 159 patients with stage I-III BC were analyzed using a personalized, tumor-informed ctDNA assay (SignateraTM bespoke mPCR-NGS assay). Of the 159 patients, 157 received standard of care NAT; the remaining 2 patients were treated with endocrine therapy only in the neoadjuvant setting. Blood samples were collected at the time of diagnosis from 71 patients (baseline) and longitudinally during treatment from 159 patients (median time between time points: 1.5 months). ctDNA status and dynamics were correlated with clinicopathological features and surgical outcomes available at the time of data cut off. Results At baseline, ctDNA was detected in 72% (51/71) of patients. Baseline ctDNA detection rates varied based on histologic subtypes: 82% (28/34) in patients with triple negative breast cancer, 88% (15/17) in patients with HER2+ disease and 40% (8/20) in patients with ER+HER2- BC. ctDNA was detectable at baseline in 72% (26/36) of patients with clinical T1-2 disease and 92% (11/12) of patients with T3-4 disease. ctDNA was detected in 64% (16/25) of patients with clinical N0, whereas among patients with at least one positive lymph node, ctDNA was detected in 92% (22/24). At baseline, 65% (31/48) of patients with low/intermediate-grade disease were ctDNA-positive, while 81% (25/31) of patients with high-grade disease were ctDNA-positive. Similarly, 83% (24/29) of patients with high levels (&amp;gt;20%) of Ki67 expression had detectable ctDNA prior to treatment initiation, while only 22% (2/9) of those with low level (&amp;lt; 20%) of Ki67 expression had ctDNA detected. Surgical outcomes were available for 22 patients of whom 16 had achieved pathologic complete response (pCR). While 3/16 pts were ctDNA negative at baseline, all of the remaining cases except one patient with baseline ctDNA detection and serial measurements (11/12) became ctDNA negative by the end of two months of treatment. Despite achieving pCR, one patient with inflammatory ER+HER2+ BC remained ctDNA positive before and after the surgery, which informed a change in the adjuvant treatment strategy. Among those with residual disease (pT1c-T3), 28% (7/25) remained ctDNA positive after two months of NAT. Association between ctDNA dynamics and surgical outcomes of the remaining 137 patients will be presented at the time of the conference. Conclusions This real world study demonstrates the prevalence of ctDNA detection and dynamics in patients with eBC treated with NAT. ctDNA monitoring during NAT can facilitate real-time assessment of treatment response and serve as an early indicator of subsequent pCR to NAT. Citation Format: Mridula George, Trishala Meghal, Coral Omene, Ekaterina Kalashnikova, Janie Fielder, Nisha Ohri, Shicha Kumar, Valeria Burkovskaya, Preena Patel, Ashley Young, Melanie Racenstein, Tinamarie Bauman, Wassim Mchayleh, Deborah Toppmeyer, Shridar Ganesan, Barry Rosen, Angel Rodriguez, Minetta Liu. Personalized circulating tumor DNA monitoring to predict response to neoadjuvant therapy in patients with early-stage breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-15-12.

Abstract PO4-19-01: The SURVIVE-HERoes trial – a secondary adjuvant treatment intervention study with trastuzumab-deruxtecan in patients with HER2 positive/HER2 low early breast cancer and a molecular relapse, based on a positive ctDNA result

Abstract Background: Despite current adjuvant treatment strategies, ≥ 20% of patients with early breast cancer (EBC) experience a metastatic relapse. In the new era of highly effective antibody drug conjugates (ADCs), secondary adjuvant treatment options for EBC patients at a high risk of relapse arise. The ADC trastuzumab-deruxtecan (T-DXd) has so far shown promising efficacy in patients with HER2-positive and HER2-low metastatic breast cancer (DESTINY Breast 03 and -04 trial) and is currently tested in the post-neoadjuvant setting in patients with non-pCR (DESTINY Breast 05 (TRUDY) trial). However, to successfully apply ADCs as a secondary adjuvant treatment, identification of patients who would benefit the most is required. The detection of minimal residual disease (MRD) using liquid biopsy, e.g. ctDNA, may offer a promising approach for patient selection. The efficacy of such a secondary adjuvant treatment in terms of delaying or even preventing distant metastases has yet to be evaluated in a randomized clinical trial. Trial design: The SURVIVE-HERoes trial is a prospective, randomized, open label comparative Phase III superiority trial in patients with intermediate to high-risk HER2-positive or HER2-low EBC, who participate in the large breast cancer surveillance trial SURVIVE (NCT05658172) and experience a molecular relapse as determined by a positive ctDNA result, but show no evidence of relapse or metastatic disease based on imaging by CT-scan and SPECT. In total, 180 patients will be enrolled and randomized with 2:1 allocation to treatment with T-DXd + (only endocrine therapy, if HR positive) versus standard of care (including endocrine treatment +/- CDK4/6-inhibitors or Neratinib). The treatment period lasts 12 months during which ctDNA levels will be repeatedly measured every 3 months (additional ctDNA testing will be performed at month 24 and 36). Stratification factors are HER2-, hormonal- and nodal status. Recruitment start is planned for Q1 2024. Eligibility criteria: Eligible patients are adult females/males, with HER2-positive or HER2-low EBC, as defined in the ASCO-CAP guidelines, and a positive ctDNA result (obtained in the SURVIVE study) that has to be confirmed ≤ 8 weeks before randomization. Primary anti-tumor therapy (surgery, adjuvant chemo- or radiotherapy) has to be completed ≥14 months, (postneo)-adjuvant treatment with anti-HER2-antibodies, T-DM1, Capecitabine, Pembrolizumab and Olaparib ≥ 4 weeks before randomization. Adequate bone marrow and cardiac function and no signs of ILD are mandatory. Statistics: The primary objective of SURVIVE-HERoes is the comparison of ctDNA clearance rates 6 months after randomization between the two study arms, which will be analysed using the chi square test for two independent proportions. Secondary objectives include the comparison of overall survival (OS), invasive disease-free survival (IDFS), distant disease-free survival (DDFS), distant recurrence-free survival (DRFS), breast cancer specific survival (BCSS), invasive breast cancer free survival (IBCFS) and quality of life (QoL) between the study arms as well as the safety and tolerability of T-DXd. Secondary survival endpoints will be estimated by the Kaplan Meier method and compared between the randomization arms using log-rank tests and cox regression models. Special aims: This trial is a proof of principle study with the aim to establish the efficacy of secondary adjuvant treatment with the ADC T-DXd in patients with HER2-positive/HER2-low early breast cancer, who are at high risk of relapse, as evidenced by detection of ctDNA in the blood. Conclusion: If SURVIVE-HERoes is successful, it could lead to a treatment shift towards early intervention with secondary adjuvant targeted therapies following liquid-biopsy based MRD detection. Contact: University Hospital Ulm, Dpt. Obstetrics &amp; Gynecology, Germany, mail: studienzentrale.ufk@uniklinik-ulm.de Citation Format: Sophia Huesmann, Franziska Mergel, Kerstin Pfister, Angelina Fink, Forca Mehmeti, Peter Möller, Tanja Fehm, Volkmar Müller, Klaus Pantel, Thomas Friedl, Andreas Hartkopf, Brigitte Rack, Wolfgang Janni. The SURVIVE-HERoes trial – a secondary adjuvant treatment intervention study with trastuzumab-deruxtecan in patients with HER2 positive/HER2 low early breast cancer and a molecular relapse, based on a positive ctDNA result [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-19-01.

Long-term clinical outcomes of hypofractionated stereotactic radiotherapy using the CyberKnife robotic radiosurgery system for jugular foramen schwannomas.

Jugular foramen schwannomas (JFSs) are rarely seen, benign tumors with slow growth. Today, management options for JFSs include observation, surgery, and radiation. However, the optimal treatment strategy remains controversial. Stereotactic radiosurgery serves as a minimally invasive alternative or adjuvant therapeutic regimen of microsurgery. Gamma Knife radiosurgery is suitable for patients with JFS who have small- and medium-sized tumors and normal cranial nerve (CN) function. Hypofractionated stereotactic radiotherapy (HSRT) offers a potential radiobiological advantage and may result in better preservation of normal structures compared to single-fraction stereotactic radiosurgery. The aim of the article was to review the clinical and radiographic outcomes of patients with JFS who were treated using HSRT. The authors retrospectively analyzed 74 patients with JFS who received HSRT between January 2009 and January 2020 in the authors' center. Among them, 53 patients were newly diagnosed with JFS, 19 patients had a previous history of microsurgical resection, and the other 2 patients underwent CyberKnife because of tumor recurrence after Gamma Knife radiosurgery. A total of 73 patients had preexisting CN symptoms and signs. The median tumor volume was 14.8 cm3 (range 0.5-41.2 cm3), and most of them (70.3%) were ≥ 10 cm3. The radiation dose regimen was prescribed depending on the tumor size, and more fractions were used in larger tumors. The median margin doses prescribed were 18.2 Gy/2 fractions, 21.0 Gy/3 fractions, and 21.6 Gy/4 fractions. The median follow-up was 103 months (range 18-158 months). After treatment, 42 (56.8%) patients had tumor regression, 27 (36.5%) patients had stable tumors, and 5 (6.8%) experienced tumor progression. Among them, MRI revealed that 1 patient had a complete response. Three patients received surgery at a median of 25 months because of tumor progression. One patient underwent ventriculoperitoneal shunt insertion for hydrocephalus that developed after HSRT independent of tumor progression. The 5-year progression-free survival rate was 93.2%. Preexisting cranial neuropathies improved in 46 patients, remained stable in 14, and worsened in 14. HSRT proved to be a safe and effective primary or adjuvant treatment strategy for JFSs, although 14 patients (18.9%) experienced some degree of delayed symptomatic deterioration posttreatment. This therapeutic option was demonstrated to provide both excellent tumor control and improvement in CN function.

A randomised double-blind placebo-controlled trial of a probiotic combination for manipulating the gut microbiota and managing metabolic syndrome

An increasing number of studies indicate that the occurrence of metabolic syndrome is significantly influenced by the host's gut microbiota and its metabolites. This study evaluated the potential application of a combination of Bifidobacterium adolescentis CCFM8630 and Lactobacillus reuteri CCFM8631 for the clinical remission of metabolic syndrome. This research comprised 40 individuals with metabolic syndrome, 21 of whom were in the probiotic intervention group and 19 in the placebo control group. The intervention duration was 11 weeks and involved the daily intake of 1 × 1010 CFU of a probiotic combination comprising Bifidobacterium adolescentis CCFM8630 and Lactobacillus reuteri CCFM8631. The serum biochemical indexes of the participants before and after the intervention were measured. After the intervention, faecal samples were collected to comprehensively analyse the gut microbiota of the participants by high-throughput sequencing and the faecal concentrations of target short-chain fatty acids by gas chromatography–mass spectrometry. The results showed that the 11-week probiotic intervention significantly reduced fasting blood glucose, fasting insulin, triglyceride, and low-density lipoprotein cholesterol concentrations in patients with metabolic syndrome and significantly increased the abundance of Bacteroidetes and some genera that produce short-chain fatty acids by regulating the abundance of gut microbial taxa that are strongly correlated with the clinical indicators of metabolic syndrome. These results demonstrated the beneficial effects of the probiotic combination on the clinical remission of metabolic syndrome, suggesting its potential application as an adjuvant strategy for the clinical treatment of metabolic syndrome in the future and laying a foundation for the further study of the mechanism of action of probiotics in alleviating metabolic syndrome.

Case Study On Pulmonary and Right Atrial Cardiac Metastases Among Children with Hepatocellular Carcinoma

The occurrence of hepatocellular carcinoma(HpC) hepato-blastoma (HB) in children with metastases in both the right atrium and lungs is a rare occurrence. Overcoming these challenges in treatment is an intricate and demanding process. We present a rare clinical case involving a pediatric patient diagnosed with hepatoblastoma (HpC) that exhibited metastasis to both the lungs and the right atrium. In response to this complex condition, surgical intervention was undertaken, complemented by a carefully administered combination of chemotherapy. This dual-phase chemotherapy, administered both pre- and post-operation, served as an adjuvant treatment strategy. The primary objective of this comprehensive therapeutic approach was to attain full remission, eliminating any traces of the malignancy. The intricacies of managing metastatic HpC in pediatric cases underscore the importance of multidisciplinary interventions, emphasizing the critical role of surgery and adjuvant chemotherapy in the pursuit of a positive treatment outcome. Thus, individuals with HB that has spread to the lungs and right atrium may have a favorable outcome by undergoing proactive and multimodal therapy.

Abstract 2902: CA-4948 (emavusertib) improves treatment response of preclinical metastatic brain melanoma to anti-PD-1 immune checkpoint blockade

Abstract Background: Although recent advances in immunotherapy for metastatic melanoma have transformed the treatment paradigm for a disease that once carried a grim prognosis, nearly 50% of patients fail to reach a complete response to immune checkpoint blockade (ICB) due to multiple mechanisms of tumor-induced immune resistance. These challenges are amplified in the CNS tumor microenvironment (TME) where metastatic brain melanoma (MBM) demonstrates diminished clinical benefit to ICB treatment. A deeper understanding of these mechanisms are required to improve therapeutic response to ICB for these patients. Our group has previously identified that aberrant activation of the myddosomal cascade through downstream interleukin (IL)-1 receptor-associated kinase (IRAK-4) signaling results in chronic stimulation of MAPK and NF-κB in MBM. Further investigation reveals myddosome signaling emanates in large part from the TME, resulting in reflexive immune suppression. CA-4948 (emavusertib), a small molecule inhibitor of IRAK-4, is capable of reaching therapeutic dose levels in the brain where it demonstrates on-target inhibition of this pathway. These data highlight a unique therapeutic opportunity where selective inhibition of immune-suppressive signaling via targeted IRAK-4 blockade may sensitize MBM to anti-PD-1 ICB. Methods Multispectral imaging of patient MBM samples were analyzed for myddosome expression in the TME. Melanoma preclinical models, including both primary site (cutaneous) and metastatic brain disease, were evaluated for tumor burden and survival in response to CA-4948 treatment alone and in combination with anti-PD-1 ICB. Immunological responses of tumor to treatment were evaluated in two transgenic reporter models, CCR2RFPCX3CR1GFP and IFNγIRES-EYFP, to determine both the distribution and activation of infiltrating immune cells. Tumor-associated myeloid cells were assessed for phenotypic markers by multiparameter flow cytometry. Results Myddosome signaling was found to be elevated in tumor-associated immune cells in patient MBM specimens. Treatment of preclinical melanoma with CA-4948 combined with anti-PD-1 ICB resulted in significantly reduced tumor growth and improved survival in three independent models. CA-4948 treatment was associated with reduced tumor recruitment of peripherally derived tumor-associated macrophages, as well as increased lymphocyte infiltration and improved pro-inflammatory signaling measured by increased IFNγ expression in the combinatorial setting. Conclusion Targeted inhibition of IRAK-4 with CA-4948 improves immune surveillance and activation in preclinical models when combined with anti-PD-1 ICB, resulting in reduced tumor growth and increased survival. Thus, CA-4948 may be an effective adjuvant treatment strategy alongside anti-PD-1 ICB for the treatment of metastatic melanoma. Citation Format: Christina A. von Roemeling, Bently P. Doonan, Amanda M. Acevedo, Jeet A. Patel, Savannah L. Carpenter, Alisha Bhatia, Reinhard W. von Roemeling, Jamison Hoffman, Maureen Lane, Duane A. Mitchell. CA-4948 (emavusertib) improves treatment response of preclinical metastatic brain melanoma to anti-PD-1 immune checkpoint blockade [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 2902.

Metagenomic analysis of the intestinal microbiome reveals the potential mechanism involved in Bacillus amyloliquefaciens in treating schistosomiasis japonica in mice.

Targeted interventions of probiotics on gut microbiome were used to explore the mechanism of alleviating schistosomiasis japonica. Through metagenomic analysis, there were significant changes in the composition of gut microbiota in mice infected with Schistosoma japonicum and significant increase in the abundance of beneficial bacteria after the intervention of Bacillus amyloliquefaciens. At the same time, the abundance of functional genes was found to change significantly. The abundance of genes related to urease metabolism and xfp/xpk related to D-erythrose 4-phosphate production was significantly restored, highlighting the importance of Limosilactobacillus reuteri in the recovery and abundance of predicted genes of the gut microbiome. These results indicated potential regulatory mechanism between the gene function of gut microbiome and host immune response. Our research lays the foundation for elucidating the regulatory mechanism of probiotic intervention in alleviating schistosomiasis japonica, and provides potential adjuvant treatment strategies for early prevention and treatment of schistosomiasis japonica.

The Effect of Body Temperature Changes on the Course of Treatment in Patients With Pneumonia and Sepsis: Results of an Observational Study.

Traditionally, patients who are critically ill with infection and fever have been treated with antipyretics or even physically cooled. Presumed benefits of the reduction of body temperature are mostly based on decreased metabolic demands. However, it has been shown that decreasing body temperature in patients who are critically ill is not associated with improvement in treatment outcomes. Additionally, there is some data to support the use of temperature modulation (therapeutic hyperthermia) as an adjuvant treatment strategy in patients with infection. This study aims to determine the effect of body temperature on the course of intensive care unit (ICU) treatment of patients who are mechanically ventilated with pneumonia, sepsis, and positive tracheal aspirates on admission. We performed a single-center retrospective study. Core body temperature was measured in all patients. We analyzed associations between average temperatures in the first 48 hours after admission to ICU and ICU treatment parameters. Additionally, patients were divided into three groups: patients with negative tracheal aspirates 1 week after ICU admission (P-N group), patients with a different pathogen in tracheal aspirates 1 week after ICU admission (P-HAP group), and patients with a persisting pathogen in tracheal aspirates 1 week after ICU admission (P-P group). Differences in body temperature and interventions aimed at temperature modulation were determined. We observed a significantly higher average temperature in the first 48 hours after admission to ICU in patients who survived to hospital discharge compared to nonsurvivors (mean 37.2 °C, SD 1 °C vs mean 36.9 °C, SD 1.6 °C; P=.04). We observed no associations between average temperatures in the first 48 hours after ICU admission and days of mechanical ventilation in the first 7 days of treatment (ρ=-0.090; P=.30), the average maximum daily requirement for noradrenaline in the first 7 days of treatment (ρ=-0.029; P=.80), average maximum FiO2 in the first 7 days of ICU treatment (ρ=0.040; P=.70), and requirement for renal replacement therapy in the first 7 days of ICU treatment (mean 37.3 °C, SD 1.4 °C vs mean 37.0 °C, SD 1.3 °C; P=.23). In an additional analysis, we observed a significantly greater use of paracetamol in the P-N group (mean 1.0, SD 1.1 g vs mean 0.4, SD 0.7 g vs mean 0.4, SD 0.8 g; P=.009), a trend toward greater use of active cooling in the first 24 hours after ICU admission in the P-N group (n=11, 44% vs n=14, 33.3% vs n=16, 32%; P=.57), and no other significant differences in parameters of ICU treatment between patient groups. We observed better survival in patients who developed higher body temperatures in the first 48 hours after admission to the ICU; however, we observed no changes in other treatment parameters. Similarly, we observed greater use of paracetamol in patients with negative tracheal aspirates 1 week after ICU admission. Our results support the strategy of temperature tolerance in patients who are intubated with pneumonia and sepsis.

Molecular classification guides for the postoperative adjuvant therapy of early-stage endometrial carcinoma

Surgical treatment has been widely used for early-stage endometrial carcinoma patients, but 15-20% of patients had a poor prognosis, requiring a postoperative adjuvant therapy. With the development of molecular classification of endometrial carcinoma, the combination of molecular and clinicopathological factors can guide the prognosis risk assessment and make the adjuvant therapy selection more accurate, as a result, the survival outcome of patients can be greatly improved. In this article, the molecular classification of endometrial carcinoma is reviewed, and its guidance to the postoperative adjuvant therapy for early-stage endometrial carcinoma is discussed. It concludes that the molecular classification opens up the opportunity of creating new ideas for adjuvant treatment strategies for early endometrial cancer.

Nanocarrier-mediated curcumin delivery: An adjuvant strategy for CNS disease treatment.

Neurological disorders are a major global challenge, which counts for a substantial slice of disease burden around the globe. In these, the challenging landscape of central nervous system (CNS) diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and neuro-AIDS, demands innovative and novel therapeutic approaches. Curcumin, a versatile natural compound with antioxidant and anti-inflammatory properties, shows great potential as a CNS adjuvant therapy. However, its limited bioavailability and suboptimal permeability to the blood-brain barrier (BBB) hamper the therapeutic efficacy of curcumin. This review explores how nanocarrier facilitates curcumin delivery, which has shown therapeutic efficacy for various non-CNS diseases, for example, cancers, and can also revolutionize the treatment outcomes in patients with CNS diseases. Toward this, intranasal administration of curcumin as a non-invasive CNS drug delivery route can also aid its therapeutic outcomes as an adjuvant therapy for CNS diseases. Intranasal delivery of nanocarriers with curcumin improves the bioavailability of curcumin and its BBB permeability, which is instrumental in promoting its therapeutic potential. Furthermore, curcumin's inhibitory effect on efflux transporters will help to enhance the BBB and cellular permeability of various CNS drugs. The therapeutic potential of curcumin as an adjuvant has the potential to yield synergistic effects with CNS drugs and will help to reduce CNS drug doses and improve their safety profile. Taken together, this approach holds a promise for reshaping CNS disease management by maximizing curcumin's and other drugs' therapeutic benefits.

Recent Advances in Adjuvant Therapy for Non-Small-Cell Lung Cancer.

After the successful development of targeted therapy and immunotherapy for the treatment of advanced-stage non-small cell lung cancer (NSCLC), these innovative treatment options are rapidly being applied in the adjuvant setting for early-stage NSCLC. Some adjuvants that have recently been approved include osimertinib for epidermal growth factor receptor-mutated tumors and atezolizumab and pembrolizumab for selected patients with resectable NSCLC. Numerous studies on various targeted therapies and immunotherapy with or without chemotherapy are currently ongoing in the adjuvant setting. However, several questions regarding optimal strategies for adjuvant treatment remain unanswered. The present review summarizes the available literature, focusing on recent advances and ongoing trials with targeted therapy and immunotherapy in the adjuvant treatment of early-stage NSCLC.

Chinese expert consensus on multigene testing for adjuvant treatment of HR-positive, HER-2 negative early breast cancer(2023 edition)

Breast cancer is the most common malignant tumor in women, of which the majority is early breast cancer (EBC). The strategy of postoperative adjuvant treatment relies mainly on the clinicopathologic characteristics of patients, but there are certain deficiencies if only depending on it to assess treatment benefits and disease prognosis. Multigene testing tools can evaluate the prognosis and predict therapeutic effects of breast cancer patients to guide the clinical decision-making on whether to use adjuvant chemotherapy, radiotherapy, and endocrine therapy by detecting the expression levels of specific genes. The consensus-writing expert group, based on the characteristics, validation results, and accessibility of the multigene testing tools and combined with clinical practice, described the result interpretation and clinical application of OncotypeDx(®) (21-gene), Mammaprint(®) (70-gene), RecurIndex(®) (28-gene), EndoPredict(®)(12-gene), and BreastCancerIndex(®) (BCI, 7-gene) for hormone receptor-positive and human epidermal growth factor receptor 2-negative EBC. The development and validation process of each tool was also briefly introduced. It is expected that the consensus will help guide and standardize the clinical use of multigene testing tools and further improve the level of precise treatment for EBC.

256P Evolution and risk stratification of adjuvant treatment strategies for early breast cancer: A Chinese perspective based on a national cancer database

256P Evolution and risk stratification of adjuvant treatment strategies for early breast cancer: A Chinese perspective based on a national cancer database

Risk factor modification as a treatment pillar in managing atrial fibrillation.

Atrial fibrillation (AF) is common, with many modifiable and nonmodifiable risk factors contributing to its increasing prevalence. Pharmacologic management and invasive procedures are the mainstays of treatment, but cardiovascular risk modification is overlooked as a key adjuvant treatment strategy. This article describes the clinical effects of implementing a risk factor modification strategy to reduce dysrhythmia load.

Longitudinal Analysis of Circulating Tumor DNA and Detection of Tumor Genomic Alterations Using Liquid Biopsy in Patients with Locally Advanced Esophagogastric Carcinoma

For locally advanced esophageal (E), esophagogastric junction (EGJ), and gastric (G) carcinoma, the standard treatment is neoadjuvant chemoradiotherapy followed by surgery. The curative goal is to control the tumor locally, prevent regional recurrence, and prevent or delay metastatic progression. Up to one-third of patients will achieve complete pathologic response rate (pCR) under this treatment. Yet disease recurrence can occur in one-third of patients after definitive treatment. Our study provides real-world longitudinal data of liquid biopsy to analyze circulating tumor deoxyribonucleotide acid (ctDNA) for minimal residual disease (MRD) as an informative marker for early therapeutic response, detectable disease, and risk for recurrence. Furthermore, the liquid biopsy reveals variable tumor-specific sequence alterations. A total of 8 patients with newly diagnosed locoregional esophagogastric cancers were evaluated with non-invasive plasma sample, collected at baseline, post-neoadjuvant chemoradiation, post-surgery, and serially as disease surveillance. Bespoke mPCR-NGS assay measured the ctDNA-based MRD levels and identified a comprehensive tumor-specific genomic profile. The primary outcome is assay recurrence compared to radiologic disease recurrence, defined as radiologic confirmed disease. Exploratory endpoints are used to examine the profile of tumor. Baseline ctDNA levels were detected in 8 newly diagnosed patients. Longitudinal testing showed a decrease in ctDNA in 4 patients and residual disease in 2 patients after the start of neoadjuvant therapy. 1 patient demonstrated pCR in conjunction with ctDNA clearance. Clearance of ctDNA may correlate to a favorable pCR and indicate a lower risk of relapse, guiding the strategy for adjuvant treatment. Personalized, tumor-informed sequence alterations of the 8 patients revealed a high frequency in TP53 alterations, which occurs early during development in esophagogastric cancer. This prospective study seeks to validate the application of ctDNA surveillance and tumor molecular alterations in a larger cohort after 5 years.