Adjuvant Treatment Strategies Research Articles

Combination of grade and spread through air spaces (STAS) predicts recurrence in early stage lung adenocarcinoma: a retrospective cohort study.

Adenocarcinomas, a common subtype of lung cancer, exhibit diverse histological patterns. In 2020, The International Association for the Study of Lung Cancer (IASLC) introduced a grading system emphasizing high-grade components, which has shown prognostic value. Spread through air spaces (STAS) is recognized as a prognostic feature increasing the risk of recurrence in lung cancer. This study evaluates the combination of STAS status and the IASLC-grading system in surgically resected Stage I lung adenocarcinomas. This study is a retrospective analysis of 123 patients with Stage I lung adenocarcinoma who underwent lobectomy between 2011 and 2019. Histological patterns were assessed according to the IASLC criteria, and STAS status was documented. Patients were categorized based on their IASLC Grade and STAS status. Statistical analyses included Kaplan-Meier survival estimates, Cox proportional hazards models, and comparisons using Chi-square and t-tests. The cohort comprised 43 females and 80 males with a mean age of 61.8 ± 7.6years. STAS positivity was noted in 52.8% of patients. STAS positivity correlated significantly with Grade 3 tumors (p < 0.001). The 5-year recurrence-free survival was significantly lower in STAS-positive patients (70.7% vs. 88.7%, p = 0.026). Patients with Grade 3 and STAS positivity had significantly lower recurrence-free survival compared to other groups (p = 0.002). Grade 3 and STAS positivity were independent predictors of poor recurrence-free survival in multivariate analysis. IASLC Grade 3 tumors and STAS positivity are independent prognostic factors for poor recurrence-free survival in Stage I lung adenocarcinomas. Adjuvant treatment strategies should be considered for patients with these characteristics to improve outcomes.

A Novel Liver Metastasis Score for Patients Undergoing Surgical Resection of Gastroenteropancreatic Neuroendocrine Tumors: A Multi-institutional Study.

Liver metastasis impacts survival in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs); however, current guidelines lack consensus on post-resection surveillance and adjuvant therapy. A comprehensive risk stratification tool is needed to guide personalized management. We aimed to develop and validate a predictive model for liver metastasis risk after surgical resection of GEP-NETs that incorporates pathological factors and adjuvant therapy. Patients with GEP-NETs who underwent surgical resection with curative intent at three major Chinese hospitals (2010-2022) were identified. Univariable and multivariable Cox regression analysis identified independent risk factors of liver metastasis. The liver metastasis score (LMS) was developed using weighted risk factors and validated by tenfold cross-validation. Among the 724 patients included in the analytic cohort, liver metastasis occurred in 66 patients (9.1%) at a median of 36 months; patients with liver metastasis had a worse 5-year overall survival (no liver metastasis 63.6% vs. liver metastasis 95.8%; p<0.001). Independent predictors were Ki-67 index (hazard ratio [HR] 10.36 for Ki-67 3-20%, HR 18.30 for Ki-67 >20%, vs. <3%), vascular invasion (HR 5.03), lymph node metastases (HR 2.24), and lack of adjuvant therapy (HR 3.03). The LMS demonstrated excellent discrimination (C-index 0.888) and stratified patients into low, intermediate, and high-risk relative to 5-year risk of liver metastasis: 2.9%, 20.8%, and 49.7%, respectively (p<0.001). The novel LMS effectively predicted the risk of liver metastasis after surgical resection of GEP-NETs. This validated model can help guide personalized surveillance and adjuvant treatment strategies, potentially improving outcomes for high-risk patients.

Recurrent symptomatic intracranial hemorrhage in high-grade astrocytoma with piloid features: illustrative case.

High-grade astrocytoma with piloid features (HGAP) is a novel condition introduced in the 2021 World Health Organization classification. Given that it has been recently classified, reports clarifying its clinical features or diagnostic criteria are lacking, especially in cases of atypical presentation. Herein, the authors present a rare case of HGAP with repeated symptomatic hemorrhages. A woman in her 20s presented with an acute headache and vertigo. Computed tomography and magnetic resonance imaging revealed a 2.5 × 2.8 × 2.3-cm hemorrhagic cerebellar mass with calcifications. After moderate improvement of her symptoms, she developed recurrent hemorrhage, and the tumor size increased (3.0 × 3.6 × 4.0 cm) 18 days later, necessitating resection. Pathological and molecular analyses confirmed the diagnosis of HGAP with an FGFR1-TACC1 fusion, MTAP/CDKN2A/B deletion, and SETD2 rearrangement. Radiologically, the presence of calcification and cystic components and the absence of perilesional edema were atypical features of previously reported HGAP. Although recurrent symptomatic intracranial hemorrhages are rare in HGAP, enhancing lesions on magnetic resonance imaging suggest the need for resection to obtain tissue for molecular diagnosis and guide adjuvant treatment strategies. https://thejns.org/doi/10.3171/CASE24395.

Exploring the anti-cancer and antimetastatic effect of Silymarin against lung cancer

Lung cancer metastasis remains a significant challenge in cancer therapy, necessitating the exploration of novel treatment modalities. Silymarin, a natural compound derived from milk thistle, has demonstrated promising anticancer properties. This work explored the inhibitory effects of silymarin on lung cancer metastasis and revealed the underlying processes, focusing on matrix metalloproteinase (MMP) 2 and MMP-9 activities. Using a combination of in vitro and molecular docking analyses, we found that silymarin effectively reducing the lung cancer cells' motility and invasion by modulation of expression of MMP-2 and MMP-9. Furthermore, MTT assays revealed a dose-dependent inhibition of cell proliferation upon silymarin treatment and found the IC50 value at 58 μM. We observe that apoptotic morphology characteristic in silymarin treated groups. Cell cycle analysis exhibit the cell cycle arrest at G1 phase, 25.8 % increased apoptosis in silymarin treated groups, as evidenced by Annexin V staining. Moreover, silymarin treatment shows the lipid peroxidation in elevated level and reduced in enzymatic antioxidant level, indicating its potential role in mitigating oxidative stress induce cell death. Gelatin zymography assay indicates the silymarin has ability to inhibit the MMP-2 and MMP-9 expression in lung cancer. Additionally, cell migration assays and colony formation assays demonstrated impaired migratory and colony-forming abilities of lung cancer cells when treated with silymarin. Molecular docking studies further supported the binding affinity of silymarin with MMP-2 and MMP-9, demonstrate the −10.26 and −6.69 kcal/mol of binding energy. Collectively, our findings highlight the multifaceted anticancer properties of silymarin against lung cancer metastasis, providing insights into its therapeutic potential as an adjuvant treatment strategy.

Engineered probiotic-mediated intratumoral delivery and controlled release of bacterial collagenase for cancer therapy

Elevated collagen levels within breast tumors are strongly associated with tumor progression and present a barrier to effective therapeutic agent penetration within the tumor microenvironment (TME), leading to poor clinical outcomes. To address this challenge, we engineered a probiotic strain to degrade collagen within the TME by selectively colonizing in tumors and releasing bacterial collagenase in a lysis-dependent manner. Initially, we constructed a therapeutic bacterial strain designed to lyse within the TME and release an encoded immunotoxin comprising a nanobody targeting CD47 (CD47nb) and a modified Pseudomonas exotoxin A (PE38KDEL). The introduction of collagenase-expressing bacteria, in conjunction with therapeutic immunotoxin, reduced collagen fiber levels within the TME, resulting in inhibited tumor growth and prolonged survival in a murine model of breast cancer. Furthermore, we investigated the broader applicability of the collagenase-expressing bacterial strain in combination with chemotherapeutic drugs, such as doxorubicin. Remarkably, synergistic antitumor effects were observed in mice treated with this combination therapy. In conclusion, our study demonstrates that probiotic delivery of bacterial collagenase offers a promising adjuvant treatment strategy for selectively degrading intratumoral collagen, thereby improving the efficacy of anticancer therapies in breast cancer.

236. THE ROLE OF ADJUVANT THERAPY FOLLOWING NEOADJUVANT CHEMORADIOTHERAPY AND ESOPHAGECTOMY IN ESOPHAGEAL CANCER

Abstract Background The objective of this study was to assess the role of adjuvant therapy following neoadjuvant chemoradiotherapy and esophagectomy in esophageal squamous cell carcinoma (ESCC). Methods We conducted a retrospective analysis involving 506 ESCC patients who underwent trimodal therapy. The clinical significance of adjuvant therapy on overall survival and disease-free survival was evaluated using Kaplan–Meier curves with log-rank tests, the Cox regression model, and a forest plot displaying hazard ratios (HR) with 95% confidence intervals. Results Among the 506 patients who had clinically positive lymph nodes and no metastasis after neoadjuvant chemoradiotherapy and esophagectomy, those who received adjuvant therapy exhibited shorter post-resection overall survival (OS) and disease-free survival (DFS), with a statistically significant difference between the two groups (Log-Rank, OS: P = 0.002; DFS: P &amp;lt; 0.001). Adjuvant therapy was not identified as an independent prognostic factor for OS (HR: 1.249; 95% CI: 0.869-1.796; P = 0.230), but it was a significantly unfavorable independent prognostic factor for DFS (HR: 1.868; 95% CI: 0.349-2.586; P &amp;lt; 0.001). Conclusion Adjuvant therapy is associated with poorer overall survival (OS) and disease-free survival (DFS) outcomes in ESCC patients with ypTNM stage I and II on final pathology following neoadjuvant chemoradiotherapy and esophagectomy. However, there was no significant difference observed in patients with ypTNM stage III or IV. Therefore, it is not recommended to undergo postoperative adjuvant therapy for patients with ypTNM stage I and II ESCC. However, for patients with ypTNM stage III and IV ESCC, further research is needed to explore adjuvant treatment strategies.

357. OUTCOMES OF TWO-COURSE NEOADJUVANT CHEMOTHERAPY WITH DOCETAXEL, CISPLATIN, AND 5-FLUOROURACIL ON ADVANCED ESOPHAGEAL CANCER: A SINGLE INSTITUTION STUDY

Abstract Background The CROSS trial established neoadjuvant chemoradiotherapy (CRT) as a cornerstone in treating esophageal cancer, making it the standard approach worldwide. However, in Japan, the JCOG1109 trial, a three-arm study, redefined the standard by showing the superiority of neoadjuvant chemotherapy (NAC) with docetaxel, cisplatin, and 5-fluorouracil (DCF) over the conventional cisplatin and 5-fluorouracil (CF) regimen. Notably, it found no significant difference between neoadjuvant CRT with CF and CF. This trial adopted a 3-week cycle of 3 courses for the DCF regimen. Nonetheless, subsequent findings by Makino et al. suggested no difference in outcomes between 2-course and 3-course DCF regimens. This report presents the results of a 2-course neoadjuvant DCF regimen at our institution. Method This study included esophageal cancer patients who underwent esophagectomy after a 2-course NAC-DCF regimen at Okayama University Hospital from January 2014 to December 2019. Eligible participants were 20 to 80 years old, with a performance status of 0–1, histologically confirmed esophageal squamous cell carcinoma (ESCC), and adequate organ function. The stages ranged from cT1-4a N0-3 M0. We evaluated recurrence patterns, overall survival (OS), and recurrence-free survival (RFS) using the Kaplan-Meier method and explored histopathological factors associated with RFS through COX regression analysis. Results Out of 209 cases, 63 were eligible. The median follow-up was 71 months, with 17 instances of recurrence observed, categorized as lymphatic (6 cases), hematinic (3 cases), local (2 cases), dissemination (2 cases), and multiple (4 cases). The 5-year RFS was 64.5%, and the 5-year OS was 65.8%. Univariate analysis identified pathological T, N, Stage, and chemotherapy response grade as significant factors related to RFS, with multivariate analysis highlighting pathological N as an independent factor. Kaplan-Meier analysis demonstrated significant survival differences across N stages, particularly between N1 and N2. Conclusion Our findings from the 2-course neoadjuvant DCF regimen highlight pathological N stage as a crucial independent predictor of recurrence in ESCC patients treated with NAC-DCF. Specifically, patients above N2 exhibited notably poorer prognoses, underscoring the need for adjuvant treatment strategies.

Quercetin alleviates depressive-like behavior by modulating acetyl-H3K9 mediated ferroptosis pathway in hypothalamus of perimenopausal depression rat model

Perimenopausal depression is a subtype of depression and is prevalent among perimenopausal women, which has brought a heavy burden to family and society. The pathogenesis of perimenopausal depression is still unclear, which affects the prevention and treatment of perimenopausal depression to a certain extent. Quercetin is a flavonoid compound, and has estrogenic activity and pharmacological effects such as antioxidant, anti-inflammatory, and neuroprotective effects. This study investigated whether quercetin improved perimenopausal depression-like behaviors and potential mechanism. The results demonstrated that quercetin could alleviate the depression-like behaviors in perimenopausal depression rat model, inhibit astrocyte activation, improve ferroptosis-associated mitochondrial damage (such as mitochondrial pyknosis and mitochondrial cristae reduction) in hypothalamus, increase the expressions of histone 3 lysine 9 acetylation (acetyl-H3K9), ferroptosis-associated protein including glutathione peroxidase 4 (GPX4) and Xc- antiporter (SLC7A11), and reduce the expressions of endoplasmic reticulum stress-related proteins including inositol-requiring enzyme 1 (IRE1α), phosphorylated IRE1α (p-IRE1α), X-box binding protein 1 (XBP1) and glucose-regulated protein 78 (GRP78) in hypothalamus of perimenopausal depression rat model. Furtherly, in vitro study indicated that quercetin could restore histone acetylase (HAT)/histone deacetylase (HDAC) homeostasis through binding to estrogen receptors and increase the expression of acetyl-H3K9, inhibiting ferroptosis through IRE1α/XBP1 pathway in astrocytes of hypothalamus. Our findings demonstrated that acetyl-H3K9 is a crucial target in development of perimenopausal depression, and quercetin exhibited antidepressant effects through modulating acetyl-H3K9 mediated ferroptosis in perimenopausal depression. Quercetin might be the prevention and adjuvant treatment strategy of perimenopausal depression.

Research progress and prospect of postoperative adjuvant therapy for resectable intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary malignancy of the liver, following hepatocellular carcinoma (HCC). Surgical resection remains the only potentially curative treatment for ICC. However, due to its high malignancy and propensity for postoperative recurrence, the prognosis for ICC is generally poor, and there is currently little standardized approach for adjuvant therapy following curative surgery. This article aims to explore adjuvant treatment strategies for ICC post-curative surgery by reviewing retrospective studies and clinical trials conducted in recent years. The analysis focuses on the effectiveness, challenges, and potential developments in the management of ICC post-surgery, considering the high recurrence rates and the need for improved therapeutic approaches to enhance patient outcomes. Additionally, we discuss the various types of adjuvant treatments that have been explored, including chemotherapy, radiation therapy, and targeted therapies. The goal is to provide a comprehensive overview of the current landscape and highlight promising directions for future research to improve survival and quality of life for ICC patients.

Optimizing adjuvant treatment strategies for non-pancreatic periampullary cancers.

Non-pancreatic periampullary tumors have long been neglected, leading to blurred adjuvant treatment strategies. Recent research, like the ISGACA group's study, is uncovering nuances in chemotherapy efficacy for these diverse cancers. Tailored approaches show promise, with artificial intelligence (AI) aiding in personalized treatment plans.

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 ≥5 cm, 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.