Rate Of Liver Metastasis Research Articles

The Effect of Metformin on Survival in Patients with Non-Small Cell Lung Cancer

Aim: Lung cancer is the most common cause of cancer- related deaths in the world. Diabetes mellitus (DM) can be seen frequently in the lung cancer patient group as well as in the normal population. Metformin is one of the most commonly used biguanide drugs in the treatment of DM. Studies conducted in patients with different types of cancer, such as breast, liver, and prostate, have shown that metformin use may contribute to survival. The aim of the study is to evaluate the effect of metformin on survival in patients with non-small cell lung cancer (NSCLC). Matherial and Methods: In this study, 85 patients diagnosed with non-small cell lung cancer and concurrent type 2 DM retrospectively were analyzed, and the last follow-up date was 31.11.2020. Neutrophil/lymphocyte ratio (NLR) of the patients was calculated. Alkaline phosphatase (ALP), lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA) values and their contribution to survival were examined. Results: The 1, 3, and 5-year overall survival rates for all patients were 76.0%, 46.5%, and 34.3%, respectively, and the median OS was 64.1 (95% CI: 44.7-83.5). Lymph node (LN) positivity, liver metastasis, and death rates were less common in the patient group receiving metformin. Overall survival (OS) results and determined survival rates were worse in the non-metformin patient group. Conclusion: Metformin usage and the control of hyperinsulinemia and hyperglycemia may contribute to survival rates. Larger and prospective studies are needed to determine the effect of metformin which is used for glycemic control and insülin resistance, in NSCLC patients' survival.

Abstract B007: Optimization of an Orthotopic Mouse Model of Pancreatic Cancer to Simulate Liver Metastasis and Cancer Cachexia

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with a poor prognosis due to two key features. The first is metastasis at presentation, occurring in approximately 80% of PDAC patients, with 90% of these metastases occurring in the liver. The second is cachexia, which compromises treatment tolerance and reduces the quality of life for patients. Although various mouse models of PDAC exist, recapitulating both metastatic and cachectic features have been challenging. In this study, we optimized an orthotopic mouse model of PDAC by altering implantation sites, subcloning parental murine PDAC cells, adjusting the number of transplanted cells, and varying the age of recipient mice to study liver metastasis and cancer cachexia. These modifications significantly increased the latency of tumor development and the time course of the disease, concurrently increasing the rate of liver metastasis to approximately 70%. Furthermore, reliable cachexia endpoints were also achieved in both PDAC mice with and without metastases, mirroring the condition in patients. We also found that cachectic muscles from PDAC mice with metastasis exhibit a similar transcriptional profile to muscles derived from mice and patients without metastasis. Together, this model is likely to be advantageous in both advancing our understanding of the mechanisms of PDAC cachexia and in evaluating novel therapeutics. Citation Format: David J Wang, Victoria Spadafora, Benjamin R Pryce, Alexander Oles, Erin E Talbert, Micheal C Ostrowski, Denis C Guttridge. Optimization of an Orthotopic Mouse Model of Pancreatic Cancer to Simulate Liver Metastasis and Cancer Cachexia [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B007.

Clinicopathological features of hepatoid adenocarcinoma and non-hepatoid adenocarcinoma of the stomach: A systematic review and meta-analysis.

Hepatoid adenocarcinoma of the stomach (HAS) is an extremely rare and unique malignant gastric tumor with a significantly worse prognosis than non-hepatoid adenocarcinoma of the stomach (non-HAS). The present study explored the clinicopathological features of HAS and non-HAS patients to provide insights into HAS treatment strategies. From December 26, 2023, we performed a comprehensive search of the PubMed, Web of Science, Cochrane Library, and Embase.com databases for relevant studies. Two authors independently screened the studies, evaluated their quality, extracted data, and performed the analyses. This study was registered with PROSPERO on January 2, 2024. Nine retrospective studies were included for analysis after screening 833 articles. A total of 350 and 924 patients were enrolled in the HAS and non-HAS groups, respectively. While no significant differences were observed in age, sex, tumor size, T3 or T4 stage, and N2 or N3 stage between the two groups, the HAS group exhibited higher rates of lymph node metastasis (OR = 1.93, 95% CI: 1.19-3.13, p = 0.007), liver metastasis (OR = 3.45, 95% CI: 2.26-5.28, p < 0.001), and vascular invasion (OR = 2.76, 95% CI: 2.05-3.71, p < 0.001). Additionally, the HAS group had lower 3-year survival rates (HR = 2.35, 95% CI: 1.70-3.25, p < 0.001) and 5-year survival rates (HR = 3.63, 95% CI: 1.49-8.88, p = 0.005), but lower rates of lymphatic permeation (OR = 0.68, 95% CI: 0.47-0.99, p = 0.040). Based on the current clinical evidence, patients with HAS present distinct clinicopathological features, greater invasiveness, and poorer prognosis than non-HAS patients. Further research is warranted to develop optimal treatment strategies for HAS.

Clinical Characteristics and Special Considerations in the Management of Rare Melanoma Subtypes.

Rare histologic subtypes of melanoma, including acral, mucosal, uveal, and desmoplastic melanomas, only make up 5% of all diagnosed melanomas and are often underrepresented in large, randomized trials. Recent advancements in systemic therapy have shown marked improvement in pathologic response rates, improving progression-free and overall survival among cutaneous melanoma patients, but there are limited data to demonstrate improved survival among rarer subtypes of melanoma. Acral melanoma has a poor response to immunotherapy and is associated with worse survival. Mucosal melanoma has a large variability in its presentation, a poor prognosis, and a low mutational burden. Uveal melanoma is associated with a high rate of liver metastasis; recent adoption of infusion and perfusion therapies has demonstrated improved survival among these patients. Desmoplastic melanoma, a high-risk cutaneous melanoma, is associated with high locoregional recurrence rates and mutational burden, suggesting this melanoma may have enhanced response to immunotherapy. While these variants of melanoma represent distinct disease entities, this review highlights the clinicopathologic characteristics and treatment recommendations for each of these rare melanomas and highlights the utility of modern therapies for each of them.

Novel Near-Infrared Fluorescent Probe for Hepatocyte Growth Factor in Vivo Imaging in Surgical Navigation of Colorectal Cancer.

Despite recent advancements in colorectal cancer (CRC) treatment, the prognosis remains unfavorable primarily due to high recurrence and liver metastasis rates. Fluorescence molecular imaging technologies, combined with specific probes, have gained prominence in facilitating real-time tumor resection guided by fluorescence. Hepatocyte growth factor (HGF) is overexpressed in CRC, but the advancement of HGF fluorescent probes has been impeded by the absence of effective HGF-targeting small-molecular ligands. Herein, we present the targeted capabilities of the novel V-1-GGGK-MPA probe labeled with a near-infrared fluorescent dye, which targets HGF in CRC. The V-1-GGGK peptide exhibits high specificity and selectivity for HGF-positive in vitro tumor cells and in vivo tumors. Biodistribution analysis of V-1-GGGK-MPA revealed tumor-specific accumulation with low background uptake, yielding signal-to-noise ratio (SNR) values of tumor-to-colorectal >6 in multiple subcutaneous CRC models 12 h postinjection. Quantitative analysis confirmed the probe's high uptake in SW480 and HT29 orthotopic and liver metastatic models, with SNR values of tumor-to-colorectal and -liver being 5.6 ± 0.4, 4.6 ± 0.5, and 2.1 ± 0.3, 2.0 ± 0.5, respectively, enabling precise tumor visualization for surgical navigation. Pathological analysis demonstrated the excellent tumor boundaries discrimination capacity of the V-1-GGGK-MPA probe at the molecular level. With its rapid tumor targeting, sustained tumor retention, and precise tumor boundary delineation, V-1-GGGK-MPA merges as a promising HGF imaging agent, enriching the toolbox of intraoperative navigational fluorescent probes for CRC.

Aprospective study of detection and clinical significance of bone marrow tumor cells in small cell lung cancer

Objective: To investigate the detection of bone marrow tumor cells in small cell lung cancer (SCLC) patients and their relationship with clinical features, treatment response and prognosis. Methods: A total of 113patients with newly diagnosed SCLC from January 2018 to October 2022 at Beijing Chest Hospital were prospectively enrolled. Before treatment, bone marrow was aspirated and separately submitted for tumor cells detection by liquid-based cytology and disseminated tumor cells (DTCs) detection by the substrction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) platform. The correlation between the detection results of the two methods with patients' clinical features and treatment response was evaluated by Chi-square. Kaplan-Meier method was applied to create survival curves and the Cox regression model was used for multivariate analysis. Results: The positive rate of bone marrow liquid-based cytology in SCLC was 15.93% (18/113). The liver and bone metastases rates were significantly higher (55.56% vs 11.58% for liver metastasis, P＜0.001; 77.78% vs 16.84% for bone metastasis, P＜0.001) and thrombocytopenia was more common (16.67% vs 2.11%, P=0.033) in patients with tumor cells detected in liquid-based cytology than those without detected tumor cells. As for SE-iFISH, DTCs were detected in 92.92% of patients (105/113), the liver and bone metastasis rates were significantly higher (37.93% vs 11.90% for liver metastasis, P=0.002; 44.83% vs 20.23 % for bone metastasis, P=0.010), and the incidence of thrombocytopenia was significantly increased (13.79% vs 1.19%, P=0.020) in patients with DTCs≥111 per 3 ml than those with DTCs＜111 per 3 ml. The positive rates of bone marrow liquid-based cytology in the disease control group and the disease progression group were 12.00% (12/100) and 46.15% (6/13), respectively, and the difference was statistically significant (P=0.002). However, the result of SE-iFISH revealed the DTCs quantities of the above two groups were 29 (8,110) and 64 (15,257) per 3 ml, and there was no statistical difference between the two groups (P=0.329). Univariate analysis depicted that the median progression-free survival (PFS) and median overall survival (OS) of liquid-based cytology positive patients were significantly shorter than those of tumor cell negative patients (6.33 months vs 9.27 months for PFS, P=0.019; 8.03 months vs 19.50 months for OS, P=0.019, P=0.033). The median PFS and median OS in patients with DTCs≥111 per 3 ml decreased significantly than those with DTCs＜111 per 3 ml (6.83 months vs 9.50 months for PFS, P=0.004; 11.2 months vs 20.60 months for OS, P=0.019). Multivariate analysis showed that disease stage (HR=2.806, 95%CI:1.499-5.251, P=0.001) and DTCs quantity detected by SE-iFISH (HR=1.841, 95%CI:1.095-3.095, P=0.021) were independent factors of PFS, while disease stage was the independent factor of OS (HR=2.538, 95%CI:1.169-5.512, P=0.019). Conclusions: Both bone marrow liquid-based cytology and SE-iFISH are clinically feasible. The positive detection of liquid-based cytology or DTCs≥111 per 3 ml was correlated with distant metastasis, and DTCs≥111 per 3 ml was an independent prognostic factor of decreased PFS in SCLC.

Multicenter randomized phase II study on S-1 and oxaliplatin therapy as an adjuvant after hepatectomy for colorectal liver metastases (YCOG1001).

The high recurrence rate of colorectal cancer liver metastasis (CRCLM) after surgery remains a crucial problem. However, adjuvant chemotherapy after hepatectomy for CRCLM has not yet been established. This study evaluated the efficacy of adjuvant therapy with S-1 and oxaliplatin (SOX). In a multicenter, randomized, phase II study, patients undergoing curative resection of CRCLM were randomly enrolled in a 1:1 ratio to either the low- or high-dose group. S-1 and oxaliplatin were administered from days 1 to 14 of a 3-week cycle as a 2-h infusion every 3weeks. The dose of S-1 was fixed at 80mg/m2. The doses in the low- and high-dose oxaliplatin groups were 100mg/m2 (low-dose group) and 130mg/m2 (high-dose group), respectively. This treatment was repeated eight times. The primary endpoint was the rate of discontinuation owing to toxicity. The secondary endpoints were the relapse-free survival (RFS) and frequency of adverse events (AEs). Between August 2010 and March 2015, 44 patients (low-dose group: 31 patients and high-dose group: 13 patients) were enrolled in the study. Of these, one patient was excluded from the efficacy analysis. In the high-dose group, five of nine patients were unable to continue the study due to toxicity in February 2013. At that time, recruitment to the high-dose group was stopped from the protocol. The relative dose intensity (RDI) for S-1 in the low- and high-dose groups were 49.8 and 48.7% (p = 0.712), and that for oxaliplatin was 75.9 and 73.0% (p = 0.528), respectively. The rates of discontinuation due to toxicity were 60 and 53.8% in the low- and high-dose groups, respectively, with no marked difference noted between the groups (p = 0.747). The frequency of grade ≥ 3 common adverse events was neutropenia (23.3%/23.1%), diarrhea (13.3%/15.4%), and peripheral sensory neuropathy (6.7%/7.7%). The disease-free survival (DFS) at 3years was 52.9% in the low-dose group, which was not significantly different from that in the high-dose group (46.2%; p = 0.705). SOX regimens as adjuvant therapy after hepatectomy for CRCLM had high rates of discontinuation due to toxicity in both groups. In particular, the RDI of S-1 was < 50%. Therefore, the SOX regimen is not recommended as adjuvant chemotherapy after hepatectomy for CRCLM.

Causes of liver test abnormalities in newly diagnosed cancer patients and the investigation of etiological factors

ABSTRACT Objectives In this study, we aimed to investigate the causes of liver test abnormalities in newly diagnosed patients naive to anti-tumoral therapy. Method This study included a total of 490 patients with ALT levels > 5X ULN on liver function tests at the initial presentation to our clinic. Data from 247 (50.4%) patients diagnosed with cancer (cohort A) and 243 (49.6%) patients without cancer (cohort B) were compared with regard to the etiology of liver test abnormalities and the risk factors. Results The most common etiological factor in cohort A was presence of liver metastasis (31.2%, n = 77). In the comparison of the two groups with regard to etiological factors; the rates of liver metastasis [31.2% vs 0%, (p < 0.001)], drug-induced liver toxicity [30/4% vs 19.8%, (p = 0.007)], pancreaticobiliary pathology [21.5% vs 14%, (p = 0.03)] and chronic viral hepatitis [14.2% vs 7.4%, (p = 0.02)] were higher in the cohort A. The rate of NAFLD was higher in the cohort B [6.9% vs 42.2% (p < 0.001). Conclusion In our study, the most common cause of liver test abnormalities was the presence of liver metastasis in cohort A and NAFLD in cohort B.

Do Histology and Primary Tumor Location Influence Metastatic Patterns in Bladder Cancer?

Metastasis is the leading cause of death in patients with bladder cancer. This study utilized a statistical analysis of patient data from the Surveillance, Epidemiology, and End Results database to examine the influence of histological type and primary site on the metastatic behavior of bladder cancer. Significantly different metastatic patterns were observed among bladder cancer patients depending on their histological type. Patients with squamous cell carcinoma showed a significantly (p < 0.001) lower bone metastasis rate (27.2%) than patients with urothelial carcinoma (UC) (38.3%). Patients with neuroendocrine carcinoma showed a significantly (p < 0.001) higher liver metastasis rate (52.1%) and a significantly (p = 0.001) lower lung metastasis rate (25.7%) than patients with UC (22.6% and 33.5%, respectively). UC patients also demonstrated differences in metastatic behavior according to histological subtype. The sarcomatoid subtype showed a significantly (p < 0.001) higher lung metastasis rate (51.6%) and a significantly lower (p = 0.002) lymph node metastasis rate (22.6%) than the micropapillary subtype (12.1% and 54.1%, respectively). Significant differences in metastatic behavior were also observed among patients with conventional UCs originating from the bladder, ureter, and renal pelvis. This study highlights the impact of histological characteristics and primary site on metastatic tendencies in bladder cancer, highlighting the importance of tailoring treatment and surveillance strategies.

The Japanese Nationwide Cohort Data of Proton Beam Therapy for Liver Oligometastasis in Breast Cancer Patients

A nationwide multicenter cohort study on particle therapy was launched by the Japanese Society for Radiation Oncology (JASTRO) in Japan. We analyzed the outcome of proton beam therapy (PBT) for liver oligometastasis in breast cancers. Cases in which PBT was performed at all Japanese proton therapy facilities between May 2016 and February 2019 were enrolled. The patients were selected based on the following criteria: the primary cancer was controlled, liver recurrence without extrahepatic tumors, and no more than three liver lesions. The treatment indication and strategy were discussed at cancer boards in each institution. The dose and fraction of PBT were determined by referring to the unified treatment policy established by JASTRO. We used the following protocol: 64 gray (Gy) (relative biological effectiveness [RBE])/8 fraction (fr) for the hepatic periphery area away from the GI tract, and 72.6 GyE/22 fr for the adjacent hilar region type. Regarding safety, the HCC irradiation protocols of 66 GyE/10 fr, 72.6-76 GyE/20-22 fr, and 74-76 GyE/37-38 fr could be used. The local control (LC), overall survival (OS), and progression free survival (PFS) rates were calculated using the Kaplan-Meier method. Factors possibly related to OS, such as tumor size, number of liver tumors, intervention of chemotherapy, and/or hormone therapy, were investigated. The cut-off values were estimated using the receiver operating characteristic curve and area under the curve. Univariate analysis was performed using the log-rank test. Fourteen females, with a median age of 57 (range, 44-73) years and twenty-two lesions were included. Nine patients had one lesion, two patients had two lesions, and three patients had three lesions. PBT was selected because nine patients had underlying disease and five patients had general conditions (age, etc.). The median lesion size, fraction size, and biological effective dose using the linear-quadratic model with α/β = 10 Gy ((BED)10) were 44 (20-130) mm, 6.6 (2-8) (relative biological effectiveness [RBE])/fraction (fr), and 109.6 (52.7-115.2) Gy, respectively. The median follow-up period of breast cancers was 22.8 (4-54) months. The 1-, 2-, and 3-year LC rates of liver metastasis from breast cancers were 100% for all. The 1-, 2-, and 3-year OS rates were 85.7%, 62.5%, and 62.5%, respectively. The 1-, 2-, and 3-year PFS rates were 50.0%, 33.3%, and 16.7%, respectively, and median PFS time was 16 months. Tumor size, the number of liver tumors, and the intervention of chemotherapy and/or hormone therapy at any time were not significantly related to the OS. Only one patient did not complete PBT due to current disease progression. The other patients completed PBT without interruption. One patient had grade 3 radiation-induced dermatitis. Based on the low incidence of adverse events and the high LC rate, PBT appears to be a feasible option for liver oligometastasis in breast cancer patients.

485. MATTHEW EFFECT OF NEOADJUVANT THERAPY IN ESOPHAGEAL CANCER

Abstract Carcinoma. Background Neoadjuvant therapy benefits long-term survival to patients with locally advanced Esophageal Squamous Cell Carcinoma (ESCC). If the survival benefit brought by neoadjuvant therapy is considered as a positive improvement for majority patients, outweighing the negative harms, it means that some patients will experience a reduction in survival due to the negative harms, just as the Matthew effect. This study focuses on these failures of Matthew effect who may not benefit from neoadjuvant therapy and explores the specific recurrent patterns. Method A total of 457 recurrent ESCC patients undergoing curative esophagectomy were enrolled, including 140 patients treated with neoadjuvant therapy. The median progression time (MPT) were 24.3 months. Tumor recurrences or metastases occurring before MPT were defined as treatment failure. We retrospectively investigated the patterns of recurrence and the prognosis in patients with neoadjuvant therapy. Results Among recurrent patients, locoregional recurrence, lung and bone metastases were the most common recurrence sites. The median progression time to the first recurrence was 24.3 months. The locoregional recurrence rate of neoadjuvant group was lower than that of none-adjuvant group (46% vs 60.2%), while the liver and brain metastasis rates was higher (16% vs 7.5% and 8.1% vs 3.3% respectively). Kaplan–Meier analysis showed unsatisfactory prognosis for neoadjuvant therapy failures than those without neoadjuvant therapy. Moreover, for non-neoadjuvant ESCC, shorter overall survival was found in distant recurrence failures than those with locoregional recurrence, while the different recurrence patterns shared similar prognosis for neoadjuvant therapy failures. Conclusion For treatment failure patients with early progression, neoadjuvant therapy has an advantage in controlling local recurrence, but this positive improvement does not transform into survival benefits, indicating Matthew effect of neoadjuvant therapy in ESCC.

FGF19-Induced Inflammatory CAF Promoted Neutrophil Extracellular Trap Formation in the Liver Metastasis of Colorectal Cancer.

Liver metastasis is the main cause of death in patients with colorectal cancer (CRC); thus, necessitating effective biomarkers and therapeutic targets for colorectal cancer liver metastasis (CRLM). Fibroblast growth factor 19 (FGF19) is a protumorigenic gene in numerous human malignancies. In this study, it is shown that FGF19 plays an indispensable role in CRLM. FGF19 expression and secretion aremarkedly correlated with liver metastasis and lower overall survival rates of patients with CRC. An in vivo metastasis model shows that FGF19 overexpression confers stronger liver-metastatic potential in CRC cells. Mechanistically, FGF19 exerts an immunomodulatory function that creates an environment conducive for metastasis in CRLM. FGF19 mediates the polarization of hepatic stellate cells to inflammatory cancer-associated fibroblasts (iCAFs) by activating the autocrine effect of IL-1α via the FGFR4-JAK2-STAT3 pathway. FGF19-induced iCAFs promote neutrophil infiltration and mediate neutrophil extracellular trap (NET) formation in liver metastatic niches via the production of complement C5a and IL-1β, which in turn accelerates the liver colonization of CRC cells. Importantly, targeting FGF19 signaling with fisogatinib efficiently suppresses FGF19-induced liver metastasis in a mouse model. In summary, thisstudy describes the mechanism by which FGF19 regulates CRLM, thereby providing a novel target for CRLM intervention.

Leveraging longitudinal clinical annotations and panel sequencing to characterize dynamics of organotropism in metastatic melanoma.

9526 Background: Although metastasis plays a major role in the mortality and morbidity of melanoma, patterns of metastasis and drivers of organotropism have not been well characterized clinically. Although previous efforts have been made to examine genomic drivers of organotropism, a longitudinal examination of metastasis dynamics has not been well characterized clinically. Methods: To address these questions, we leveraged a clinico-genomic dataset of patients with metastatic melanoma (Kehl et al. 2021). From this dataset, we assembled a cohort consisting of 26,143 artificial intelligence-annotated imaging reports from 879 patients with metastatic melanoma with an average of 2 years of followup after initial metastatic diagnosis. Annotated metastasis sites included brain, bone, adrenal, liver, lymph node, lung, and mesentery. All patients were evaluated at the Dana-Farber Cancer Institute, and each patient has at least one tumor biopsy sequenced with OncoPanel, a next-generation sequencing panel that identifies mutations in 447 cancer-related genes. Lifetime incidence of metastatic sites was defined as whether a patient ever had a report annotated with that site. Time-to-event analyses on metastatic sites used the acquisition of a metastatic site as the event of interest. For each patient index dates were defined as the date of the first scan with cancer present. We used cumulative incidence models to examine the incidence of each site in our cohort, and both cause-specific hazard models and Fine-Gray modeling to account for competing events and determine the effect of genomic covariates. Results: For lifetime metastasis status, the overall incidence varied by site, with LN being the most common, occurring in ~75% of patients, and mesentery the rarest, occurring in ~12% of patients. For lifetime metastasis status, patients with adrenal metastases were positively enriched for mutations in SETD2 (P &lt; 0.005). Among the significant genes for all sites were many genes encoding epigenetic modifiers. In the time-to-event setting, the order of the cumulative incidence functions for each site matched the lifetime frequency of sites. Through time-to-event analysis we found genes whose mutant status were significantly associated with a change in risk and/or rate of certain metastatic sites. Among other results, we found that having a mutation in SETD2 is significantly positively associated with an increase rate and risk of adrenal metastases (cause-specific HR 2.4, P &lt; 0.005, Fine-Gray HR 2.6, P &lt; 0.005), and NRAS mutations were significantly associated with lower rate and risk of liver metastasis (cause-specific HR 0.59 P &lt; 0.05, Fine-Gray HR 0.58 P &lt; 0.01). Conclusions: By using time-to-event analysis with longitudinal metastatic annotations, we identify potential drivers of organotropism in melanoma patients.

Evaluation of liver metastasis in patients with breast cancer: Comparison of single-phase abdominopelvic CT and multi-phase liver CT.

To compare the usefulness of multi-phase liver CT and single-phase abdominopelvic CT (APCT) in evaluating liver metastasis in newly diagnosed breast cancer patients. In this retrospective study, a total of 7621 newly diagnosed breast cancer patients (mean age, 49.7years ± 10.1; 7598 women) who underwent single-phase APCT (n = 5536) or multi-phase liver CT (n = 2085) for staging workup between January 2016 and June 2019 were included. The staging CTs were categorized as having no metastasis, probable metastasis, or indeterminate lesions. MRI referral rate (proportion of patients underwent additional liver MRI), negative MRI rate (patients without true hepatic metastasis / patients underwent liver MRI), true positive CT rate (patients with true metastasis / patients categorized as probable metastasis), true metastasis rate among CT indeterminate (patients with true metastasis / patients categorized as indeterminate lesions), and overall liver metastasis rate were compared between the two groups. Further, the radiation dose was recorded for every patient. The proportions of having no metastasis and indeterminate lesions on the results of CT interpretation were significantly different between the two groups (P = 0.006). However, the MRI referral rate, negative MR rate, true positive CT rate, true metastasis rate among CT indeterminate, and overall liver metastasis rate were not significantly different between the two groups. Radiation dose of multi-phase CT was three times higher than that of single-phase CT. Multi-phase liver CT has little benefit over single-phase APCT in assessing liver metastasis in patients with breast cancer.

Abstract PD7-06: Characteristics of Long-Term Survival in Breast Cancer Brain Metastasis after Stereotactic Radiation

Abstract Background: Advances in imaging and systemic therapy have improved the survival for patients with breast cancer brain metastases (BCBM). However, an improved understanding of patients with long-term survival after stereotactic radiation (SRT) for BCBM is warranted and could allow for better prognostication and personalized treatment. Methods: This is a single institution retrospective review of 188 patients who underwent SRT sessions to 685 BCBM from August 2004 to June 2020. Patients who were lost to follow up within 2 years after SRT were excluded. Patients were stratified into 2 groups: those with overall survival (OS) from SRT less than 2 years (short-term survival, STS) and those with OS from SRT of at least 2 years (long-term survival, LTS). Patient, tumor, and treatment characteristics were compared between the 2 groups via the student t-test and Chi-square testing as appropriate. The Kaplan-Meier (KM) method was used to calculate OS, local control (LC), and distant intracranial control (DIC) from the date of SRT. The reverse KM method was used to estimate follow-up from SRT. Results: The median follow up from BCBM diagnosis was 52.8 months (95% CI: 40.5-75.2 months). Of the 685 treated BCBMs, 552 (81%) received stereotactic radiosurgery (SRS) to a median dose of 21 Gy (12-24 Gy) and 133 received fractionated stereotactic radiation therapy (FSRT) to a median dose of 25 Gy (20-35 Gy) in 3-5 fractions. The 2-year LC, DIC, and OS was 78.4%, 26.5%, and 38.3%, respectively. The 5-year OS was 19%. There were 72 patients (38%) in the LTS group and 116 patients (62%) in the STS group. The LTS group had lower rates of invasive lobular carcinoma (0% vs 6%, p=0.001) and higher rate of HER2+ disease (61% vs 30%, p&amp;lt; 0.001). The LTS group had lower rates of concurrent extracranial metastasis (74% vs 89%, p=0.008) and lung metastasis (33% vs 53%, p=0.009), though there were no differences in the rates of bone or liver metastasis. The LTS group had less BCBM at the time of SRT (mean 1.9 vs 2.5, p=0.013) and more often received SRT to a single BCBM (65% vs 42%, p=0.002). There were no significant differences in age or performance status between the groups. Conclusion: Prognosis for patients with BCBM is heterogeneous, as a minority of patients have prolonged OS after SRT. These patients more often have limited BCBM, HER2+ disease, and a lower extracranial disease burden. Citation Format: Joseph D. Tang, Matthew N. Mills, Chetna Thawani, Daniel E. Oliver, Aixa Soyano, Arnold Etame, Hsiang-Hsuan Michael Yu, Nam Tran, Michael A. Vogelbaum, Peter A. Forsyth, Brian J. Czerniecki, Hatem H. Soliman, Hyo S. Han, Kamran A. Ahmed. Characteristics of Long-Term Survival in Breast Cancer Brain Metastasis after Stereotactic Radiation [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD7-06.

Exploring the relationships between hormone receptor, HER2 status, and bone involvement in the first distant metastases of in Chinese breast cancer patients who lacked HER2 targeted therapy

BackgroundThis retrospective study explored the relationship between hormone receptor (HR), human epidermal growth factor receptor 2 (HER2) status, and bone involvement in the first distant metastases (DM) of Chinese breast cancer (BC) patients who lacked the HER2 targeted therapy. Such therapy was rarely received due to its lag approval or high cost in China compared with the developed countries.MethodsAll eligible women with primary unilateral stage I – III BC and first DM diagnosed in 2008—2018 at one cancer center were identified for enrollment. Based on chart records, a full or no/partial compliance status of endocrine therapy (ET) was assigned for HR-positive patients. Multivariate logistic regression was used to estimate the adjusted odd ratio (aOR), its 95%CI and p value.ResultsFour hundred eighteen patients had an average age of 50.7 years and median disease-free survival of 27.1 months at DM. Bone, lung, liver and brain metastasis rates in patients were 55.7%, 34.7%, 33.0% and 8.1%, respectively. Compared to HR-negative patients, HR-positive patients with the full and non/partial compliance of ET were significantly associated with higher risk of bone involvement with an aOR of 2.329 (1.316 – 1.741, p = 0.004) and 2.317 (1.330 – 4.036, p = 0.003), respectively. No difference of such risk was found between the two groups of ET compliance (p = 0.984) nor between HER2-negative and HER2-positive patients (aOR 0.827, p = 0.431). Stratified analyses further indicated that HR-positive was associated with bone involvement only in HER2-negative BC patients (p = 0.006—0.015).ConclusionsHR-positive tumors are significantly associated with bone involvement in HER2-negative metastatic BC patients. ET does not appear to impact this association. HER2 status per se is not associated with such risk.

Long Term Outcomes of No-Touch Isolation Principles Applied in Pancreaticoduodenectomy for Treatment of Pancreatic Adenocarcinoma: A Multicenter Retrospective Study with Propensity Score Matching.

Background: The recurrence and liver metastasis rates are still high in pancreatic head cancer with curative surgical resection. A no-touch isolation principle in pancreaticoduodenectomy (PD) may improve this situation, however, the exact advantages and efficacy of these principles have not been confirmed. Materials and methods: Among 370 patients who underwent PD, three centers were selected and classified into two groups: the no-touch PD group (n = 70) and the conventional PD group (n = 300). Propensity score matching was used to control for selection bias at a ratio of 1:1. The confounding variables were age, sex, body mass index, adjuvant chemotherapy, carbohydrate antigen 19-9, tumor size and tumor differentiation. Results: Patients in the no-touch PD group had better overall survival (OS) and disease-free survival (DFS) than those in the conventional PD group (OS: 17 vs. 13 months, p = 0.0035, DFS: 15 vs. 12 months, p = 0.087), with lower 1- and 2-year disease-related mortality rates (1-year: 32.9% vs. 47%, p = 0.032; 2-year: 42.5% vs. 82% p = 0.000) and recurrence and liver metastasis rates (1-year: 30.0% vs. 43.3%, p = 0.041; 2-year: 34.3% vs. 48.7%, p = 0.030). Compared with the matched conventional PD group, the no-touch PD group also had a better OS (17 vs. 12 months, p = 0.032). Conclusions: Our study showed the no-touch isolation principle may be a better choice to improve long-term survival for pancreatic cancer patients.

Not all Rectal Cancer Patients Could Benefit From the Surgery on the Primary Site.

Previous studies have provided evidence that primary site surgery can improve the prognosis of rectal cancer patients, even in those with advanced age and distant metastasis, though results have been inconsistent. The current study aims to determine if all rectal cancer patients are likely to benefit from surgery in terms of overall survival. This study examined the impact of primary site surgery on the prognosis of rectal cancer patients diagnosed between 2010 and 2019 using multivariable Cox regression analysis. The study also stratified patients by age group, M stage, chemotherapy, radiotherapy, and number of distant metastatic organs. The propensity score matching method was used to balance observed covariates between patients who received and did not receive surgery. The Kaplan-Meier method was used to analyze the data, and the log-rank test was used to determine differences between patients who did and did not undergo surgery. The study included 76,941 rectal cancer patients, with a median survival of 81.0months (95% CI: 79.2-82.8months). Of these patients, 52,360 (68.1%) received primary site surgery, and they tended to be younger, have higher differentiated grade, earlier T, N, M stage, and lower rates of bone, brain, lung, and liver metastasis, chemotherapy, and radiotherapy than those without surgery. Multivariable Cox regression analysis revealed that surgery had a protective effect on the prognosis of rectal cancer patients, including those with advanced age, distant metastasis, and multiple organ metastasis, but not in patients with four organ metastases. The results were also confirmed using propensity score matching. Not all rectal cancer patients could benefit from the surgery on the primary site, especially the patients with more than four distant metastases. The results could help the clinicians to tailor targeted treatment regimens and provide a guideline for making surgical decisions.

Classification of rectal cancer according to recurrence types - comparison of Japanese guidelines and Western guidelines.

Rectal cancer is characterized by more local recurrence (LR) and lung metastasis than colon cancer. However, the diagnosis of rectal cancer is not standardized as there is no global consensus on its definition and classification. The classification of rectal cancer differs between Japanese and Western guidelines. To clarify the characteristics of rectal cancer by comparing the tumor location and characteristics of rectal cancer with those of colon cancer according to each set of guidelines. A total of 958 patients with Stage II and III colorectal cancer were included in the analysis: 607 with colon cancer and 351 with rectal cancer. Localization of rectal cancers was assessed by enema examination and rigid endoscopy. According to Japan guidelines, rectal cancer is classified as Rb (below the peritoneal inversion), Ra (between the inferior margin of second sacral vertebrae and Rb) or RS (between Ra and sacral promontory). There were no significant differences between RS rectal cancer and colon cancer in the rates of liver and lung metastasis or LR. Lung metastasis and LR were significantly more common among Rb rectal cancer (in Japan) than in colon cancer (P = 0.0043 and P = 0.0002, respectively). Lung metastases and LR occurred at significantly higher rates in rectal cancer measuring ≤ 12 cm and ≤ 10 cm than in colon cancers (P = 0.0117, P = 0.0467, P = 0.0036, P = 0.0010). Finally, the rates of liver metastasis, lung metastasis, and LR in rectal cancers measuring 11 cm to 15 cm were 6.9%, 2.8%, and 5.7%, respectively. These were equivalent to the rates in colon cancer. High rectal cancer may be treated with the same treatment strategies as colon cancer. There was no difference in the classification of colorectal cancer between Japan and Western countries.

Low Expression of SNAI1 in Lymph Node Metastasis Indicates Delayed Recurrence of Colonic Cancer.

Even though epithelial-mesenchymal transition markers in primary tumors are identified as a helpful indicator of cancer metastasis and prognosis, their expression in lymph node metastases (LNMs) remains poorly described. We aimed to investigate the difference between snail family transcriptional repressor 1 (SNAI1) and E-cadherin expression in primary tumors and LNMs, and how it affects prognosis. From 2010 to 2014, 127 patients who underwent radical surgery for stage III colonic adenocarcinoma without preoperative treatment were retrospectively reviewed for SNAI1 and E-cadherin expression in primary tumors and LNMs. High SNAI1 expression was found in 76% and 70% of primary tumors and LNMs, respectively, and low E-cadherin expression was found in 73% and 84%, respectively. High expression of SNAI1 in LNMs significantly correlated with poor overall and relapse-free survival rates. Even though the rate of liver metastasis at 5 years was similar for the groups with high and low SNAI1 expression in LNMs, the incidence in the group with low SNAI1 expression in the second year was higher than that in the first year (33% vs. 17%), whilst in the group with high SNAI1 expression, the incidence in the first year was higher than in the second year (71% vs. 29%). The rate of recurrence of lung metastasis was significantly lower when SNAI1 expression in LNMs was low (p=0.031). Low expression of SNAI1 in LNMs of colonic adenocarcinoma may indicate delayed recurrence in the liver and lung.