Metastasis In Patients Research Articles

Effect of circulating tumor cells (CTC) and CTC clusters with PD-L1 dynamic biomarker on cellular burden in patients with ovarian cancer.

e17566 Background: In the precision oncology era, monitoring response to the treatments using circulating blood-based biomarkers e.g. circulating tumor DNA (ctDNA) and Circulating Tumor Cells (CTCs) are being rapidly evaluated and established. The leading cause of ovarian cancer patient mortality is owing to the delayed diagnosis, inability of patient selection for targeted therapies, including the use of immune checkpoint blockade (ICB) agents. The treatment of ovarian cancer usually involves a combination of surgery and chemotherapy. However, post operative resection and therapy with curative intent often fails in accounting the Minimal Cellular Disease (MCD). The dissemination of Circulating Tumor Cells (CTC) remains a dogma of Minimal Residual Disease (MRD) that diffuse and cause micro-metastasis through their epithelial to mesenchymal transitions (EMT) and ‘bio-mechanistic activation’ in blood circulation. Simultaneous detection of over-expression of Programmed Cell Death-Ligand 1 (PD-L1) on CTCs as a dynamic biomarker may be expedient for assessing patients for immune checkpoint inhibitor (ICT) therapy. Methods: In retrospective analysis of real-world data, 75 ovarian cancer patient’s peripheral blood was analyzed for the presence of CTCs with and without the expression of PD-L1 and CTC clusters. CTC were positively detected using OncoDiscover platform approved by CDSCO in 1.5 ml peripheral blood. The platform is multifunctional magneto nanosystem mediated by anti-epithelial cellular adhesion molecule (EpCAM) antibody. CTCs were identified as positive if they were EpCAM +ve, CK+ve, PD-L1 +ve, DAPI +ve and CD45-ve. PD-L1 expression on the CTCs was analyzed based on the linear intensity gradients of the fluorescence signals using image acquisition on an automated Zeiss Microscope. Results: At baseline sample analysis, 86 % (n=65) of the patients showed ≥ 1CTCs per 1.5 ml of blood. The CTC distribution in this study ranged from 1-9 CTCs. Whereas, 46.15 % (n=30) patients with CTCs showed the expression of PD-L1. Noteworthy, the highest number of CTCs were observed ~ 26.7 % (n=23) in age group 41-50. Interestingly, 8 % (n=6) of total patients showed the presence of CTC clusters. The presence of CTCs with expression of PD-L1 and CTC clusters did not correlate with factors like staging, follow ups, metastasis, and DFS status. Conclusions: We observed presence of MCD and MRD in CRC patients, in spite of curative intent in ovarian cancers. Detection of CTCs, CTC clusters with over-expression of PD-L1- as a real time dynamic biomarker may be useful for assessing the patients for early metastasis, regression, and selecting patient suitable for immune checkpoint inhibitor (ICT) therapy when the tissue is inadequate or unavailable for better outcome.

The clinical, molecular, and therapeutic implications of time from primary diagnosis to brain metastasis in lung and breast cancer patients

AbstractPurposeLung cancer (LC) and breast cancer (BC) are the most common causes of brain metastases (BMs). Time from primary diagnosis to BM (TPDBM) refers to the time interval between initial LC or BC diagnosis and development of BM. This research aims to identify clinical, molecular, and therapeutic risk factors associated with shorter TPDBM.MethodsWe retrospectively reviewed all diagnosed LC and BC patients with BM at Harbin Medical University Cancer Hospital from 2016 to 2020. A total of 570 patients with LC brain metastasis (LCBM) and 173 patients with breast cancer brain metastasis (BCBM) patients who met the inclusion criteria were enrolled for further analysis. BM free survival time curves were generated using Kaplan–Meier analyses. Univariate and multivariate Cox regression analyses were applied to identify risk factors associated with earlier development of BM in LC and BC, respectively.ResultsThe median TPDBM was 5.3 months in LC and 44.4 months in BC. In multivariate analysis, clinical stage IV and M1 stage were independent risk factors for early development of LCBM. LC patients who received chemotherapy, targeted therapy, pulmonary radiotherapy, and pulmonary surgery had longer TPDBM. For BC patients, age ≥ 50 years, Ki67 ≥ 0.3, HER2 positive or triple‐negative breast cancer subtype, advanced N stage, and no mastectomy were correlated with shorter TPDBM.ConclusionsThis single‐institutional study helps identify patients who have a high risk of developing BM early. For these patients, early detection and intervention could have clinical benefits.

First-line serplulimab plus HLX04 and XELOX versus placebo plus bevacizumab and XELOX in metastatic colorectal cancer: A phase 2/3 study.

3569 Background: This is a randomized, double-blind, multicenter phase 2/3 study comparing the efficacy and safety of serplulimab (a novel anti-PD-1 antibody) plus HLX04 (an approved bevacizumab biosimilar) and XELOX chemotherapy vs. placebo plus bevacizumab and XELOX as first-line treatment for metastatic colorectal cancer (mCRC). Interim analysis presented at the 2024 ASCO Gastrointestinal Cancers Symposium showed improvement in progression-free survival (PFS), and duration of response (DOR) for the serplulimab arm. Here we present the updated results with an extended follow-up duration of 24.2 months and the subgroup analysis results. Methods: In the phase 2 part, 114 patients with mCRC and no prior systemic therapy were randomized 1:1 (serplulimab arm, n = 57; placebo arm, n = 57) to receive intravenous (IV) serplulimab (300 mg) plus HLX04 (7.5 mg/kg) and XELOX (IV oxaliplatin [130 mg/m2] and oral capecitabine [1000 mg/m2]) (group A) or placebo plus bevacizumab and XELOX (group B) once every 3 weeks. Stratification factors were PD-L1 expression level, ECOG PS score, and primary tumor site. The primary endpoint was independent radiological review committee (IRRC)-assessed PFS per RECIST 1.1. Secondary endpoints included other efficacy endpoints, safety, pharmacokinetics, biomarker explorations, and quality-of-life assessments. Results: By the data cutoff of December 15, 2023, continuing improvements in PFS (16.8 vs. 10.7 months; stratified HR 0.62, 95% CI 0.33–1.12) and DOR (19.4 vs. 12.6 months; stratified HR 0.33, 95% CI 0.13–0.85) were observed for group A compared to group B. 55/112 (49.1%) patients in the efficacy evaluable set has died; 24/55 (43.6%) patients in group A and 31/57 (54.4%) in group B. Median overall survival (OS) was not reached (NR) in group A, and 21.2 months in group B (stratified HR 0.75, 95% CI 0.43–1.30). Subgroup analysis showed similar trends towards an improved median OS for key subgroups including microsatellite stable (MSS) (NR vs. 21.2 months; stratified HR 0.73, 95% CI 0.39–1.37), KRAS-mutant (21.9 vs. 18.2 months; unstratified HR 0.72, 95% CI 0.37–1.39), and liver metastasis (NR vs. 20.2 months; unstratified HR 0.75, 95% CI 0.40–1.41) patients. The estimated OS rate at 2 years was 53.7% (95% CI 39.1–66.2), and 43.1% (95% CI 29.5–55.9) in group A, and group B, respectively. 38 (69.1%) patients in group A and 34 (59.6%) in group B had grade ≥3 treatment-related adverse events. Serplulimab/placebo-related deaths occurred in 2 (3.6%) patients in group A and 1 (1.8%) patient in group B. Conclusions: With an extended follow-up duration, improved survival benefits demonstrated with the addition of serplulimab were maintained in the first-line treatment of mCRC, alongside a manageable safety profile. These results support serplulimab plus HLX04 and XELOX as a promising first-line treatment option for mCRC that warrants further investigation. Clinical trial information: NCT04547166 .

Melanoma brain metastasis treated with stereotactic radiosurgery (SRS) and systemic agents (SACT): A single centre perspective from Northeast England.

e21500 Background: Melanoma incidence rates in the UK will increase and given its proclivity for brain metastasis, it will be a growing challenge. Real-world survival data reflecting the impact of modern SACTs and SRS is lacking. Here we report our single-centre experience. Methods: All melanoma brain metastasis patients treated with both SRS and SACT in Newcastle-upon-Tyne, UK between January 2017 and January 2022 were identified. Data was collected from patient records until data-lock in January 2023. Survival analysis was performed using R (version 4.2.2). The primary objective was to measure the overall survival. Results: 51 patients were included. The median age was 60 years. Most patients had ECOG PS of 0 (43%, n = 22) or 1 (53%, n = 27). 15 (29%) had de-novo brain metastasis. 21 (41%) were on SACT before diagnosis of brain metastasis. 28 (55%) patients had solitary brain metastasis. 8 (16%) had no radiologically reported extracranial disease. Superficial spreading melanoma was the most common histological subtype (45%, n = 23). 55% (n = 26) had a sensitizing BRAF mutation. 25 patients (49%) received SRS before SACT. 12 (26%) patients had undergone primary debulking surgery. The median time to start SRS was 54 days (IQR 35 - 90) from brain metastasis diagnosis. Median extracranial progression-free survival was 25 months (95% CI 10 – NA). Median intracranial progression-free survival was 29 months (95% CI 15 – NA). 17 (33%) patients had both intra and extracranial progression. 7 (13%) had in-field intracranial progression. The median target volume was similar between subgroups that had infield (1.78mL, IQR 0.56 - 13.81), out-of-field (1.78mL, IRQ 1.62 - 3.97) or no intracranial progression (2.38mL, IQR 1.29 - 6.73). The median total dose to target was 21 Grays for all subgroups. Median overall survival was 27 months (95% CI 16 - NA). With intracranial progression, the median overall survival was 21 months (95% CI 10 –36). The survival was 15 months (95% CI 9.5 - 27) with extracranial progression, which was significantly less than without extracranial progression (HR = 0.25, 95% CI 0.11 – 0.60, p = 0.002). In the absence of intracranial progression, median overall survival was not reached. Patients with infield progression had an overall survival of 8.6 months (95% CI 6.8 – NA), HR 2.83 (95% CI 1.20 - 6.7), p = 0.018. Those with melanoma-specific Graded Prognostic Assessment score (molGPA) > 2.5 had a median overall survival of 31 months (95% CI 14 – NA) with a HR of 0.73 (95% CI 0.32 - 1.64, p = 0.4). Conclusions: Survival in our cohort is notably better than reports from prior series. This is despite our catchment in the North East of England being adversely affected by health disparity. This could be explained by the selection bias of our cohort. However, in the wake of improved treatment modalities, the need for more up-to-date cancer data tracking cannot be overstated.

Risk factors and clinical significance of lower perigastric lymph node metastases in Siewert type II and III esophagogastric junction adenocarcinoma: a retrospective cohort study

BackgroundNo consensus has been concluded with regarding to the scope of lymph node (LN) dissection for Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG). This study aimed to explore risk factors for lower perigastric LN (LPLN) metastases (including no. 4d, 5, 6, and 12a LN stations) and analyze the indications for LPLN dissection.MethodsIn total, 302 consecutive patients with Siewert type II and III AEG who underwent total gastrectomy (TG) were enrolled. The logistic regression model was used to perform uni- and multivariate analyses of risk factors for LPLN metastases. Kaplan–Meier curves were used for survival analysis, and log-rank tests were used for group comparisons. Basing on the guidelines of Japanese Gastric Cancer Association, the LN metastases (LNM) as well as the efficiency index (EI) of each LN station was further evaluated.ResultsThe independent risk factors for LPLN metastases in patients with Siewert type II and III AEG were distance from the esophagogastric junction (EGJ) to the distal end of the tumor (> 4.0 cm), preoperative carcinoembryonic antigen (CEA) ( +), pT4 stage, and HER-2 ( +). LPLN metastases was an independent risk factor for overall survival following TG. The LNM and EI of LPLN were 8.6% and 2.31%, respectively. The LNM of LPLN > 10% under the stratification of the distance from the EGJ to the distal end of the tumor (> 4.0 cm), pT4, preoperative CEA ( +), and HER-2 ( +) exhibited EI values of 3.55%, 2.09%, 2.51%, and 3.64%, respectively.ConclusionsLPLN metastases was a malignant factor for the prognosis of patients with Siewert type II and III AEG. For patients with preoperative CEA ( +), pT4 stage, HER-2 ( +), and the distance from the EGJ to the distal end of the tumor (> 4.0 cm), TG with LPLN dissection is prioritized for clinical recommendation.

Clinical‑imaging‑radiomic nomogram based on unenhanced CT effectively predicts adrenal metastases in patients with lung cancer with small hyperattenuating adrenal incidentalomas

Clinical‑imaging‑radiomic nomogram based on unenhanced CT effectively predicts adrenal metastases in patients with lung cancer with small hyperattenuating adrenal incidentalomas

P.091 Synthetic data reliably reproduces brain tumor primary research data

Background: Synthetic data has garnered heightened attention in contemporary research due to confidentiality barriers and its capacity to simulate variables challenging to obtain. This study aimed to evaluate the reliability and validity of synthetic data in the context of neuro-oncology research, comparing findings from two published studies with results from synthetic datasets. Methods: Two published neuro-oncology studies focusing on prognostic factors such as serum albumin and systemic inflammation scores were selected, and their methodologies were replicated using MDClone Platform to generate five synthetic datasets for each. We used Chi-Square test to assess inter-variability between synthetic datasets. Survival outcomes were evaluated using Kaplan-Meier and t-test was used to determine statistical significance. Results: Findings from synthetic data consistently matched outcomes from both original articles, with serum albumin and systemc inflammation scores correlating with survival prognosis in glioblastoma and metastasis patients (p<0.05) Reported findings, demographic trends and survival outcomes showed significant similarity (P > 0.05) with synthetic datasets. Conclusions: Synthetic data consistently reproduced the statistical attributes of real patient data. Integrating synthetic data into clinical research offers excellent potential for providing accurate predictive insights without compromising patient privacy. In neuro-oncology, where patient follow-up pose challenges, the adoption of synthetic datasets can be transformative.

Abdominal Parietal Metastasis from Cervical Cancer: A Review of One of the Most Uncommon Sites of Recurrence Including a Report of a New Case.

Cervical cancer is the fourth most common cancer in women, the highest mortality being found in low- and middle-income countries. Abdominal parietal metastases in cervical cancer are a very rare entity, with an incidence of 0.1-1.3%, and represent an unfavorable prognostic factor with the survival rate falling to 17%. Here, we present a review of cases of abdominal parietal metastasis in recent decades, including a new case of a 4.5 cm abdominal parietal metastasis at the site of the scar of the former drain tube 28 months after diagnosis of stage IIB cervical cancer (adenosquamous carcinoma), treated by external radiotherapy with concurrent chemotherapy and intracavitary brachytherapy and subsequent surgery (type B radical hysterectomy). The tumor was resected within oncological limits with the histopathological result of adenosquamous carcinoma. The case study highlights the importance of early detection and appropriate treatment of metastases in patients with cervical cancer. The discussion explores the potential pathways for parietal metastasis and the impact of incomplete surgical procedures on the development of metastases. The conclusion emphasizes the poor prognosis associated with this type of metastasis in cervical cancer patients and the potential benefits of surgical resection associated with systemic therapy in improving survival rates.

Complications Rate and Related Factors After Laparoscopic Sphincter-Preserving Total Mesorectal Excision for Low Rectal Cancer: A Single-Center Study in Vietnam.

Colorectal cancer is a significant health concern. Surgery remains a critical component of the multimodal treatment strategy. The laparoscopic sphincter-preserving total mesorectal excision (TME) is increasingly utilized and effective, offering enhanced quality of life for patients compared to previous traditional methods. This study aims to determine the rate of complications and the related factors associated with complications following laparoscopic sphincter-preserving total mesorectal excision for low rectal cancer. This retrospective study was conducted at the University Medical Center of Ho Chi Minh City from March 2022 to March 2023. It included patients aged 18 years and older diagnosed with low rectal cancer who underwent laparoscopic sphincter-preserving total mesorectal excision. Data on patient demographics, surgical details, and postoperative complications were retrospectively collected and analyzed. Follow-ups were conducted up to six months after surgery. Of the 83 patients included, the postoperative complications rate was 14.5%. The complications observed included surgical wound infections (five cases), anastomotic leaks (five cases, including three recto-vaginal fistulas and two pelvic abscesses), urinary retention (one case), and pneumonia (one case). A significant finding was the higher rate of distant metastases in patients with complications compared to those without (p=0.033). Laparoscopic sphincter-preserving total mesorectal excision for low rectal cancer is safe and effective, with a high success rate and low complication rate during or after surgery. Anastomotic leakage remains the most significant complication. Despite advancements in surgery, modern suturing tools, and preoperative patient optimization, complications are avoidable. Therefore, understanding the related factors and implementing preventive interventions is crucial.

Development and internal validation of machine-learning models for predicting survival in patients who underwent surgery for spinal metastases.

A retrospective study. This study aimed to develop machine-learning algorithms for predicting survival in patients who underwent surgery for spinal metastasis. This study develops machine-learning models to predict postoperative survival in spinal metastasis patients, filling the gaps of traditional prognostic systems. Utilizing data from 389 patients, the study highlights XGBoost and CatBoost algorithms̓ effectiveness for 90, 180, and 365-day survival predictions, with preoperative serum albumin as a key predictor. These models offer a promising approach for enhancing clinical decision-making and personalized patient care. A registry of patients who underwent surgery (instrumentation, decompression, or fusion) for spinal metastases between 2004 and 2018 was used. The outcome measure was survival at postoperative days 90, 180, and 365. Preoperative variables were used to develop machine-learning algorithms to predict survival chance in each period. The performance of the algorithms was measured using the area under the receiver operating characteristic curve (AUC). A total of 389 patients were identified, with 90-, 180-, and 365-day mortality rates of 18%, 41%, and 45% postoperatively, respectively. The XGBoost algorithm showed the best performance for predicting 180-day and 365-day survival (AUCs of 0.744 and 0.693, respectively). The CatBoost algorithm demonstrated the best performance for predicting 90-day survival (AUC of 0.758). Serum albumin had the highest positive correlation with survival after surgery. These machine-learning algorithms showed promising results in predicting survival in patients who underwent spinal palliative surgery for spinal metastasis, which may assist surgeons in choosing appropriate treatment and increasing awareness of mortality-related factors before surgery.

Location of metastasis and complications in patients with venous thromboembolism and cancer: systematic review

According to current guidelines, patients with venous thromboembolism (VTE) and active cancer should receive prolonged anticoagulant treatment (>6 months). In patients with cancer-associated thrombosis (CAT), metastasis is a factor in recurrent VTE and bleeding; however, the function of metastasis location remains unclear. In order to assess the risk of complications (such as bleeding or recurrent VTE) based on the location of metastases in patients with CAT, we conducted a systematic review. The PubMed database search was used to perform a systematic review. MESH terms pertaining to metastasis, VTE, and neoplasms were employed. Patients with CAT who were at least eighteen years old and receiving therapeutic doses of anticoagulants were included, as were details regarding the locations of metastases and the availability of patients who had complications (bleeding or recurrent VTE). Among the 1,447 articles found by the search, 7 retrospective studies met all eligibility requirements and were added to the analysis. The majority of these studies addressed brain metastases. Studies found that intracranial hemorrhage occurred between 4% and 19% of the time. In the context of brain metastases and VTE, other studies examined the safety and effectiveness of direct oral anticoagulants in comparison to low-molecular-weight heparin. This systematic review draws attention to the paucity of data regarding the impact of metastasis location on complications in CAT patients. Further research is required to assess the effect of metastasis location on the risk of VTE complications in patients with CAT.

The development of brain metastases in patients with different therapeutic strategies for metastatic renal cell cancer.

A diagnosis of brain metastasis (BM) significantly affects quality of life in patients with metastatic renal cell cancer (mRCC). Although systemic treatments have shown efficacy in mRCC, active surveillance (AS) is still commonly used in clinical practice. In this single-center cohort study, we assessed the impact of different initial treatment strategies for metastatic RCC (mRCC) on the development of BM. All consecutive patients diagnosed with mRCC between 2011 and 2022 were included at the Erasmus MC Cancer Institute, the Netherlands, and a subgroup of patients with BM was selected. In total, 381 patients with mRCC (ECM, BM, or both) were identified. Forty-six patients had BM of whom 39 had metachronous BM (diagnosed ≥1 month after ECM). Twenty-five (64.1%) of these 39 patients with metachronous BM had received prior systemic treatment for ECM and 14 (35.9%) patients were treatment naive at BM diagnosis. The median BM-free survival since ECM diagnosis was significantly longer (p = .02) in previously treated patients (29.0 [IQR 12.6-57.0] months) compared to treatment naive patients (6.8 [IQR 1.0-7.0] months). In conclusion, patients with mRCC who received systemic treatment for ECM prior to BM diagnosis had a longer BM-free survival as compared to treatment naïve patients. These results emphasize the need for careful evaluation of treatment strategies, and especially AS, for patients with mRCC.

Abstract PO2-27-09: Clinical impact of routine MRI screening for brain metastases in patients with HER2 positive or triple negative metastatic breast cancer

Abstract Background: Routine screening for brain metastases (BMs) is currently not recommended in patients with metastatic breast cancer (BC). There is a growing consensus on the need for the screening of BMs in HER2 positive and triple negative breast cancer (TNBC) because 40% of patients experience BMs throughout the disease course and systemic treatment options with intracranial efficacy are now available. However, there is a lack of prospective study data on this matter. We conducted a prospective cohort study to evaluate the role of brain MRI screening for the patient with metastatic BC. Methods: Patients who newly diagnosed metastatic HER2+ or TNBC were eligible. Screening brain MRI was planned at diagnosis and failure from first line and second line of systemic therapy. All patients underwent complete physical examination and comprehensive neurologic assessment at baseline and thereafter. Patients who diagnosed symptomatic BMs were dropped from the study and subsequent treatment including local therapies and survival data were collected. Primary endpoint was the percentage of patients diagnosed with asymptomatic BMs. Results: A total of 147 patients were enrolled between Sep 2018 and Aug 2023 at Yonsei Cancer Center. The median age was 51 years (range, 29-80) and most patients (92.5%, n=136) had good performance status (ECOG 0-1). The tumor subtypes were as follows: TNBC, 51.0%; HER2 (ER-, HER2+), 29.3%; luminal-HER2 (ER+, HER2+), 19.7%. The cumulative incidence of asymptomatic BMs was 20.4% for overall patients; 24.0% for TNBC (18/75), 14.0% for HER2 (6/43), and 20.7% for luminal HER2 (6/29). Symptomatic detection of BMs during study period was 14.7% for TNBC, 18.6% for HER2, and 6.9% for luminal-HER2. Initial local treatment was stereotactic radiosurgery in 30 patients (58.8%), whole-brain radiation therapy in 14 patients (27.5%), surgical resection in 2 patients (3.9%) and 6 patients (11.8%) did not receive any treatment for BMs. After a median follow-up of 20.1 months, the median overall survival following a diagnosis of BMs was 23.7 vs 7.3 months (hazard ratio 0.41; 95% CI, 0.17 to 0.95; P = .04) in patients with asymptomatic and symptomatic BMs, respectively. Conclusions: We identified approximately 20% of patients with HER2+ or TNBC as asymptomatic BMs. Emerging systemic therapies showed promising intracranial response would warrant the detection of asymptomatic BMs through routine MRI screening. Incidence of brain metastases by subtypes Citation Format: Gun Min Kim, Joo Hyuk Sohn, Min Hwan Kim, Seul-Gi Kim, Hyung Soon Park, Jong Hee Jang, Yong Bae Kim, Seung-koo Lee. Clinical impact of routine MRI screening for brain metastases in patients with HER2 positive or triple negative metastatic 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 PO2-27-09.

Preoperative assessment of lymph nodal metastases with [68Ga]Ga-DOTATOC PET radiomics for improved surgical planning in well-differentiated pancreatic neuroendocrine tumours.

Accurate identification of lymph node (LN) metastases is pivotal for surgical planning of pancreatic neuroendocrine tumours (PanNETs); however, current imaging techniques have sub-optimal diagnostic sensitivity. Aim of this study is to investigate whether [68Ga]Ga-DOTATOC PET radiomics might improve the identification of LN metastases in patients with non-functioning PanNET (NF-PanNET) referred to surgical intervention. Seventy-two patients who performed preoperative [68Ga]Ga-DOTATOC PET between December 2017 and March 2022 for NF-PanNET. [68Ga]Ga-DOTATOC PET qualitative assessment of LN metastases was measured using diagnostic balanced accuracy (bACC), sensitivity (SN), specificity (SP), positive and negative predictive values (PPV, NPV). SUVmax, SUVmean, Somatostatin receptor density (SRD), total lesion SRD (TLSRD) and IBSI-compliant radiomic features (RFs) were obtained from the primary tumours. To predict LN involvement, these parameters were engineered, selected and used to train different machine learning models. Models were validated using tenfold repeated cross-validation and control models were developed. Models' bACC, SN, SP, PPV and NPV were collected and compared (Kruskal-Wallis, Mann-Whitney). LN metastases were detected in 29/72 patients at histology. [68Ga]Ga-DOTATOC PET qualitative examination of LN involvement provided bACC = 60%, SN = 24%, SP = 95%, PPV = 78% and NPV = 65%. The best-performing radiomic model provided a bACC = 70%, SN = 77%, SP = 61%, PPV = 60% and NPV = 83% (outperforming the control model, p < 0.05*). In this study, [68Ga]Ga-DOTATOC PET radiomics allowed to increase diagnostic sensitivity in detecting LN metastases from 24 to 77% in NF-PanNET patients candidate to surgery. Especially in case of micrometastatic involvement, this approach might assist clinicians in a better patients' stratification.

Abstract PO5-16-04: Tissue-informed personalized MRD detection assay may outperform tumor-informed fixed panel strategy in Triple Negative Breast Cancer (TNBC)

Abstract Background: Minimal residual disease (MRD) detection by ctDNA analysis enables identifying patients with high recurrence risk and refining risk stratification to guide treatment selection precisely, which may improve patient survival or avoid overtreatment. We previously developed a 1021-gene fixed panel MRD detection assay, MNavigator V1, demonstrating high prognostic evaluation value in various solid tumors, including lung cancer, colorectal cancer, and esophageal carcinoma, and relevant research results have been published. Recently, the assay upgraded to MNavigator V2, a customized patient-specific panel strategy to ultra-deep sequencing, with higher clinical performance and more economical. Here, we head-to-head compared the performance of MNavigator V1 with V2, using the same collection of blood samples from TNBC patients. Methods: The retrospective study recruited 48 patients diagnosed with stage II~III TNBC with adequate samples (NCT04501523/NCT04803539). Five patients in the cohort received neoadjuvant therapy (Neoad-group), and the standard treatment regimen of the remaining 43 patients was adjuvant therapy (ad-group) after surgery. The surgical tumor tissue of all these patients was collected. Peripheral blood samples were collected at various time points, baseline samples before neoadjuvant therapy, 7-day after neoadjuvant therapy, 1-month postoperative, 7-day after adjuvant therapy, and subsequent every 3~6 months follow-up. The personalized, tumor-informed MRD detection approach MNavigator V2 started by identifying somatic mutation of the resected tumor with a 1021-gene panel covering 1.6Mb of the human genome. Then, a customized panel consisting of up to 20 top-ranked patient-specific somatic variants was designed. After that, unique molecular identifiers (UMI) based 100,000X ultra-deep next-generation sequencing on plasma samples was conducted by adopting the mix panel of the patient-specific panel and a 5kb breast cancer universal core panel. MNavigator V1 assay, a fixed panel assay also applied the same off-the-shelf 1021-genes panel with a sequencing depth of 10,000X to detect MRD of blood samples. Results: Until May 2023, the median follow-up time of 660 days, and 8 patients were recurrence confirmed by CT imaging. The median tracked tissue-informed mutations was 7 (2~18). In this study, the screening time point was defined as the combined MRD status of the blood samples collected before and after neoadjuvant therapy, and 1-month post-surgery for the Neoad-group, as for the ad-group, the time point referred to 1-month post-surgery and post-adjuvant therapy. If any one of these time nodes' MRD was positive, the screening period MRD was positive. During the screening period, MNavigator V1 and V2 accurately predicted 6/8 (75.0%) recurrence. MRD-positive status was associated with a worse prognosis, compared to the MRD-negative population, with hazard ratios of 9.0 and 19.9 for V1 and V2 assay, respectively. The longitudinal MRD evaluation yield a higher sensitivity of 7/8 (87.5%) for recurrence prediction with MNavigator V2 at a median lead time of 104 days, whereas the V1 assay predicted 6/8 (75.0%) at 94 days, and the hazard ratio was 40.4 vs 8.5. In one brain-only metastasis patient, MRD was undetectable, which may be due to the limitation of the blood-brain barrier. For recurrence-free patients with 1 year of follow-up, 92.5% (37/40) were MRD-negative with MNavigator V2 assay. These three patients who detected MRD-positive after surgery, ctDNA cleared after adjuvant therapy, and persistently negative during follow-up, may benefit from treatment. Conclusion: Based on the patient-specific tumor mutation profile, the personalized MRD detection assay achieved better clinical performance than the fixed panel strategy. Citation Format: Shunying Li, Wei Gao, Ning Fu, Wuqiang Cao, Xiaoling Zeng, Xinhua Du, Qiang Liu. Tissue-informed personalized MRD detection assay may outperform tumor-informed fixed panel strategy in Triple Negative Breast Cancer (TNBC) [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 PO5-16-04.

LINC02257 regulates colorectal cancer liver metastases through JNK pathway

BackgroundLong noncoding RNAs (lncRNAs) have emerged as critical regulators of colorectal cancer (CRC) progression, but their roles and underlying mechanisms in colorectal cancer liver metastases (CRLMs) remain poorly understood. MethodsTo explore the expression patterns and functions of lncRNAs in CRLMs, we analyzed the expression profiles of lncRNAs in CRC tissues using the TCGA database and examined the expression patterns of lncRNAs in matched normal, CRC, and CRLM tissues using clinical samples. We further investigated the biological roles of LINC02257 in CRLM using in vitro and in vivo assays, and verified its therapeutic potential in a mouse model of CRLM. ResultsOur findings showed that LINC02257 was highly expressed in metastatic CRC tissues and its expression was negatively associated with overall survival. Functionally, LINC02257 promoted CRC cell growth, migration, metastasis, and inhibited cell apoptosis in vitro, and enhanced liver metastasis in vivo. Mechanistically, LINC02257 up-regulated phosphorylated c-Jun N-terminal kinase (JNK) to promote CRLM. ConclusionsOur study revealed that LINC02257 played a key role in the proliferation and metastasis of CRC cells through the LINC02257/JNK axis. Targeting this axis may represent a promising therapeutic strategy for the treatment of liver metastases in patients with CRC.

Audit of Presentation, Primary Site, and Pattern of Treatment in 778 Indian Patients with Brain Metastasis in 15 Years (2007–2022)

Background and Aim: Audit of brain metastasis (BM) patients treated with radiation therapy (RT) in a tertiary cancer center from South India was carried out to assess the incidence of BM by site with a specific focus on their primary origin, with an aim to evaluate the relationship between the primary site and the site of metastases, pattern of care, and RT over the years. Materials and Methods: All consecutive BM patients who received RT with whole-brain radiation therapy (WBRT), hippocampal avoidance WBRT (HA-WBRT), and radiosurgery SRS between 2007 and 2022 after radiologic confirmation of a known case of malignancy or histology-proven BM were audited. Results: From January 2007 to December 2022, hospital information system (HIS)-identified 778 patients with BM treated with RT were audited. Incidence of BM was 0.64% in 2008 and over the years, it had increased to 0.89% in 2020, 0.93% in 2021, and 1.24% in 2022. Usage of SRS was almost nil in 2007, whereas in 2022, it was 40%. Also, 593 (76%) patients were treated with WBRT, 157 (20%) with SRS, and only 23 (3%) received HA-WBRT. Lung and breast cancers (40%) were the most common primary, and among rare primary tumors were those of larynx (two), tonsil (one), tongue (three), pancreas (one), and blood disorders (two). Lung primary presented with frontal lesion in 51%, parietal lesion in 43%, cerebellar lesion in 38%, and temporal lesion in 33% of cases. Conclusions: Audit of BM in the Indian population suggests a shift in treatment paradigm from WBRT to SRS as a primary modality in oligo-brain metastasis with a good performance status. This audit provides us information regarding geographic variation in presentation and primary site.

Impact of Empowerment Theory-Based Nursing Intervention on the Quality of Life and Negative Emotions of Patients Diagnosed with Brain Metastasis Post Breast Cancer Surgery.

This study explores the impact of a nursing intervention grounded in empowerment theory, focusing on behavioral change, on brain metastasis patients post-breast cancer surgery. Between June 2021 and June 2023, 102 patients diagnosed with brain metastasis after breast cancer surgery at Bao Ding No.1 Central Hospital were randomized into two groups. The control group (51 patients) received standard nursing care, while the observation group (51 patients) participated in a behavioral change nursing intervention influenced by empowerment theory. The evaluation metrics included measures of negative emotions, compliance with treatment protocols, overall quality of life, and nursing satisfaction, assessed at multiple time points during the study period. The intervention led to significant reductions in negative emotions for all patients when compared to their pre-intervention statuses, with the observation group exhibiting notably lower depression and anxiety scores at one and three months post-intervention (P < 0.05). Additionally, this group achieved higher compliance scores and demonstrated greater improvements in quality of life than the control group (P < 0.05). Nursing satisfaction was also significantly higher in the observation group, with 96.08% reporting high satisfaction compared to 80.39% in the control group (P < 0.05). Implementing a nursing intervention that emphasizes behavioral changes and leverages empowerment theory significantly enhances the quality of life, reduces negative emotions, boosts compliance with treatment, and increases nursing satisfaction among patients with brain metastasis following breast cancer surgery. This suggests that such interventions could be a valuable component of postoperative care for this patient population.

Prediction of the treatment response and local failure of patients with brain metastasis treated with stereotactic radiosurgery using machine learning: A systematic review and meta-analysis.

Stereotactic radiosurgery (SRS) effectively treats brain metastases. It can provide local control, symptom relief, and improved survival rates, but it poses challenges in selecting optimal candidates, determining dose and fractionation, monitoring for toxicity, and integrating with other modalities. Practical tools to predict patient outcomes are also needed. Machine learning (ML) is currently used to predict treatment outcomes. We aim to investigate the accuracy of ML in predicting treatment response and local failure of brain metastasis treated with SRS. PubMed, Scopus, Web of Science (WoS), and Embase were searched until April 16th, which was repeated on October 17th, 2023 to find possible relevant papers. The study preparation adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The statistical analysis was performed by the MIDAS package of STATA v.17. A total of 17 articles were reviewed, of which seven and eleven were related to the clinical use of ML in predicting local failure and treatment response. The ML algorithms showed sensitivity and specificity of 0.89 (95% CI: 0.84-0.93) and 0.87 (95% CI: 0.81-0.92) for predicting treatment response. The positive likelihood ratio was 7.1 (95% CI: 4.5-11.1), the negative likelihood ratio was 0.13 (95% CI: 0.08-0.19), and the diagnostic odds ratio was 56 (95% CI: 25-125). Moreover, the pooled estimates for sensitivity and specificity of ML algorithms for predicting local failure were 0.93 (95% CI: 0.76-0.98) and 0.80 (95% CI: 0.53-0.94). The positive likelihood ratio was 4.7 (95% CI: 1.6-14.0), the negative likelihood ratio was 0.09 (95% CI: 0.02-0.39), and the diagnostic odds ratio was 53 (95% CI: 5-606). ML holds promise in predicting treatment response and local failure in brain metastasis patients receiving SRS. However, further studies and improvements in the treatment process can refine the models and effectively integrate them into clinical practice.

Ultrasound and clinical factors predicting central lymph node metastases in patients with unilateral multifocal papillary thyroid carcinoma.

This retrospective study involving a large dataset of unilateral multifocal papillary thyroid carcinoma (UM-PTC) sought to identify factors that predict central lymph node metastases (CLNM) in patients. We identified a cohort of 158 patients who underwent cervical ultrasonography followed by UM-PTC diagnosis based on postoperative pathology. The relationship between CLNM and UM-PTC clinical ultrasound features was evaluated using univariate and multivariate analyses. Receiver operating characteristic (ROC) curve analysis was used to determine the ability of total tumor diameter (TTD) to predict CLNM. Among the 158 UM-PTC patients, the incidence of CLNM was 29.7% (47/158). Univariate and multivariate analyses revealed that a number of similarity of sonographic features (NSSF) ≥4 (odds ratio [OR]=11.335, 95% confidence interval [CI]: 3.95-32.50, p=0.000), microcalcifications (OR=3.54, 95% CI: 1.30-9.70, p=0.014), a TTD of ≥2cm (OR=4.48, 95% CI: 1.62-12.34, p=0.004), number of nodules ≥3 (OR=13.17, 95% CI: 3.24-53.52, p=0.000), and Lateral cervical lymph node metastasis (LLNM) (OR=5.57, 95% CI: 1.59-19.48, p=0.007) were independently associated with CLNM in UM-PTC. ROC curve analysis revealed that the TTD cut-off of 1.795cm had a sensitivity of 0.723 and a specificity of 0.676 for predicting CLNM. Patients with UM-PTC are at high risk of CLNM. NSSF ≥4, microcalcifications, TTD of ≥2cm, LLNM, and a number of nodules ≥3 were independently associated with CLNM. Our data show that ultrasound may guide surgical decisions in the treatment of UM-PTC.