Poor Prognostic Factor For OS Research Articles

Abstract PO4-05-02: The clinical impact of NOLUS in unresectable/metastatic hormone receptor-positive (HR+)/HER2-negative breast cancer

Abstract Background A non-luminal disease score (NOLUS) is pathology-based predictive model to identify PAM50 non-luminal disease within HR+/HER2-negative breast cancer. NOLUS is a new model, therefore, its clinical utility is not sufficiently elucidated. In this study, the clinical impact of NOLUS was investigated in unresectable/metastatic estrogen receptor (ER) positive (ER+)/HER2-negative breast cancer. Patients and Methods The total of 61 patients, who were diagnosed unresectable/metastatic ER+/HER2-negative breast cancer between 2010 and Apr 2023, were included in this study. A NOLUS status was calculated with formula:−0.45∗ER −0.28∗PR +0.27∗Ki67 + 73.02 and diagnosed as NOLUS-positive (≥51.38) and NOLUS-negative (< 51.38) according to the previous reports (Pascual T et al, Front Oncol 2019; 9:303). The relationships between NOLUS status and clinicopathological factors and the prognosis were analyzed. Results Among 61 patients, 10 patients (16.4%) were NOLUS-positive and 51 (83.6%) were NOLOS-negative. NOLUS-positivity was significantly associated with progesterone receptor (PgR)-negativity (p=0.0051) and higher histological grade (0.0234), and had tendency to have shorter recurrence free interval and liver metastasis. NOLUS-positivity was not associated with age, menopausal status and the Ki67. The proportion of the patients whose first line treatment for unresectable/metastatic was endocrine therapy with or without targeted therapy was higher in the NOLUS-negative group. NOLUS-positivity was significantly associated with shorter overall survival (OS; log-rank p=0.0012). Uni- and multivariate analysis, NOLUS-positivity was the poor prognostic factor for OS. Conclusion The prognosis in of the patients with NOLUS-positive unresectable/metastatic HR+/HER2-negative breast cancer was significantly poor. NOLUS is useful to predict the prognosis of these patients. Table. NOLUS and clinicopathological characteristics. NOLUS-positivity was significantly associated with progesterone receptor (PgR)-negativity (p=0.0051) and higher histological grade (0.0234), and had tendency to have shorter recurrence free interval and liver metastasis. NOLUS-positivity was not associated with age, menopausal status and the Ki67. Table. Univariate and multivariate analysis for OS after recurrence NOLUS-positivity was significantly associated with shorter overall survival (OS; log-rank p=0.0012). Uni- and multivariate analysis, NOLUS-positivity was the poor prognostic factor for OS. Citation Format: Wakako Tajiri, Yoshiaki Nakamura, Junji Kawasaki, Yumiko Koi, Sayuri Akiyoshi, Chinami Koga, Eriko Tokunaga. The clinical impact of NOLUS in unresectable/metastatic hormone receptor-positive (HR+)/HER2-negative 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 PO4-05-02.

Survival outcomes of lung metastases from colorectal cancer treated with pulmonary metastasectomy or modern systemic chemotherapy: a single institution experience

BackgroundAlthough pulmonary metastasectomy is an accepted treatment strategy for resectable lung metastases (LM) from colorectal cancer (CRC), its survival benefits are controversial. In contrast, recent advancements in chemotherapy have significantly improved metastatic CRC prognosis. This study aimed to evaluate survival outcome of LM from CRC in the age of newly developed chemotherapy.MethodsWe retrospectively reviewed 50 patients who underwent complete resection and 22 patients who received chemotherapy as definitive treatment for LM from resected CRC at our hospital. The present study was limited to patients who started treatment for isolated LM after molecular targeted drugs became available in Japan.ResultsOverall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS) rates after pulmonary resection were 64.5%, 66.4%, and 32.6% at five years, respectively. OS and CSS rates of chemotherapy patients were 26.8% and 28.3% at five years, with a median progression-free survival time of 10.0 months. When compared the characteristics of surgical and chemotherapy patients, patients with pN factors of CRC (p = 0.013), smaller size (p < 0.001), larger number (p < 0.001), and bilateral (p < 0.001) LM received chemotherapy. Univariate analysis showed that multiple LM and rectal lesions were poor prognostic factors for OS (p = 0.012) and DFS (p = 0.017) in surgical patients, and rectal lesions were a poor prognostic factor for OS (p = 0.013) in chemotherapy patients.ConclusionsPulmonary metastasectomy showed a favorable survival in patients with LM from CRC. Despite the high recurrence rate after metastasectomy and recent advances in chemotherapy, surgical resection could still be considered as a valid option among multidisciplinary treatments.Trial registrationThe research plan was approved by the Institutional Review Board of Shinko Hospital (No. 2142) on February 7, 2022.

Neoadjuvant chemotherapy for borderline resectable colorectal cancer liver metastases: a single-institution retrospective study

IntroductionThis study aimed to extract prognostic factors in patients undergoing neoadjuvant chemotherapy (NAC) for borderline resectable colorectal liver metastasis (BR-CRLM) (tumor size ≥5 cm, number of tumors ≥4, or resectable extrahepatic diseases) and assess validity of this strategy. Materials and methodsSince 2010, patients with BR-CRLM were treated with hepatectomy after six cycles of NAC. Prognostic factors of these patients were evaluated using clinicopathological data. ResultsOf 650 patients who underwent initial hepatectomy for CRLM from 2010 to 2018, 246 BR-CRLM cases underwent hepatectomy after NAC (BR-NAC). The 5-year recurrence-free survival rate was 16.7% and the 5-year overall survival rate (5y-OS) was 52.9%. Number of tumors ≥6, carcinoembryonic antigen (CEA) level ≥25 ng/mL, tumor diameter ≥5 cm, and progressive disease (PD) after NAC were identified as independent poor prognostic factors for OS. Patients were divided into four groups according to the number of risk factors, and prognoses of the four groups were well stratified. ConclusionIn patients with BR-NAC, number of tumors ≥6, CEA ≥25 ng/mL, tumor diameter ≥5 cm, and PD after NAC were independent poor prognostic factors. Patients with three or four risk factors showed poor prognosis and may need to switch chemotherapy.

Clinical Features and Outcomes of the Patients with B-Cell Chronic Lymphoproliferative Disease in the New Drug Era

To analyze the clinical characteristics of the patients with B-cell chronic lymphoproliferative disease（B-CLPD） in the new drug era and the effect of new drug treatment on efficacy and survival. The clinical and laboratory data of 200 cases B-CLPD patients diagnosed between April 2015 and August 2021 were analyzed retrospectively. The clinical efficacy and survival of the patients under different treatments including Bruton tyrosine kinase（BTK） inhibitors， rituximab， and chemotherapy alone were analyzed. The prognostic factors affecting the survival of patients were analyzed by univarite analysis and multivariate analysis. There were 119 male（59.5％） and 81 female（40.5%） in 200 cases B-CLPD patients， the sex ratio(male/female) was 1.5∶1 with median age of 61（30- 91） years old. The distribution of subtypes were as fallows: 51 cases (25.5%) of chronic lymphocytic leukemia/small lymphocytic lymphoma（CLL/SLL）， 64（32.0%） cases of follicular lymphoma（FL）， 40（20.0%） cases mantle cell lymphoma（MCL）， 30（15.0%） cases of marginal zone lymphoma（MZL）， 10（5%） cases of lymphoplasmacytic lymphoma/waldenstrom macroglobulinemia（LPL/WM）， 5（2.5%） cases of B cell chronic lymphoproliferative disorders unclassified（B-CLPD-U） . The main clinical manifestation of 102 patients was lymph node enlargement, 32 cases were complicated with B symptoms. Among CLL/SLL patients， there were 12（23.5%） cases in Binet A and 39（76.5%） cases in Binet B/C. There were 29 patients（20.9%） in Ann Arbor or Lugano stage I-II and 110 cases（79.1%） in stage III-IV of other subtypes. The complete remission（CR） rate was 43.1%（25/58）， 40.2%（39/97）， 7.1%（1/14）， and overaIl response rate（ORR） was 87.9%（51/58）， 62.9%（61/97）， 28.6%（4/14） in the groups of BTK inhibitors， rituximab-based therapy， and chemotherapy alone. The 3-year OS rate and PFS rate in all patients was 79.2% and 72.4% respectively. The 3-year OS rate of patient with MZL, CLL/SLL, FL,WM was 94.7%, 87.7%, 86.8% and 83.3% respectively, while the 3-year OS rate of MCL was only 40.6%, which was significantly lower than other subtypes. The median OS of patients treated with BTK inhibitors and rituximab-based therapy was 20.5 and 18.5 months respectively， and the 3-year OS rate was 97.4% and 90.7%. However， the median PFS of patients receiving chemotherapy alone was 4 months， and the 1-year OS rate was 52.7%， which was statistically significant compared with the other two groups（P<0.05）. Univarite analysis showed that anemia， elevated lactate dehydrogenase， elevated β2-microglobulin， and splenomegaly were the poor prognostic factors for OS（P<0.05）， elevated lactate dehydrogenase was also poor prognostic factors for PFS（P<0.05）. Multifactor analysis showed that anemia and elevated lactate dehydrogenase were the independent poor prognostic factors for survival（P<0.05）. The clinical features of B-CLPD was various， anemia and elevated lactate dehydrogenase are the prognostic factors for poor survival. BTK inhibitors and new immunotherapy can improve the survival and prognosis of patients in the new drug era.

Conditional Survival After Hepatectomy for Colorectal Liver Metastasis: Results from the Colorectal Liver Operative Metastasis International Collaborative (COLOMIC).

Complete resection of colorectal liver metastasis (CLM) improves long-term survival in colorectal cancer. However, there is limited recent data on conditional survival (CS) as postoperative survival milestones are achieved post-hepatectomy. A retrospective analysis was performed on the penta-institutional Colorectal Liver Operative Metastasis International Collaborative (COLOMIC), with 906 consecutive CLM hepatectomy cases. CS was calculated using Bayes' theorem and Kaplan-Meier analysis. Additional CS analyses were performed on additional clinicopathologic risk factors, including colon cancer laterality, KRAS mutation status, and extrahepatic disease. The 5-year CS was 40.6%, 45.3%, 52.8%, and 65.3% at 0, 1, 2, and 3 years postoperatively, with significant improvements each year (p < 0.005). CS was not significantly different between right-sided and left-sided colorectal cancers by 3 years postoperatively. Patients with KRAS mutations had worse CS at all timepoints (p < 0.001). Extrahepatic disease was a poor prognostic factor for OS and CS (p < 0.001). However, CS for patients with KRAS mutations or extrahepatic disease improved significantly as 2-year, postoperative survival was achieved (p < 0.05). Five-year CS after hepatectomy for CLM improved with each passing year of survival postoperatively. Although extrahepatic disease and KRAS mutations are poor prognostic factors for OS, these populations still had improved CS after 2 years postoperatively.

Preoperative serum interleukin-6 level in head and neck cancer reflects systemic inflammatory response and is a predictor of postoperative prognosis.

The outcome of head and neck cancer has improved in recent years but survival is not yet satisfactory. Interleukin (IL)-6 is a representative inflammatory cytokine and inducer of systemic inflammatory response. It is not known whether preoperative serum level of IL-6 is a prognostic factor in head and neck cancer surgery. We studied 181 consecutive patients who underwent head and neck surgery with free tissue transfer reconstruction (HNS-FTTR) between September 2016 and December 2020. Whether preoperative serum IL-6 level was a prognostic risk factor was retrospectively investigated by univariate and multivariate analyses. We also investigated the association between preoperative IL-6 level and representative systemic inflammatory response markers. The preoperative IL-6≥8pg/mL group had a significantly worse prognosis than the preoperative IL-6<8pg/mL group (overall survival [OS]: hazard ratio [HR] 3.098, P=0.0006; disease-specific survival [DSS]: HR 3.335, P=0.0008). In multivariate analysis, IL-6≥8pg/mL and age≥70years were independent poor prognostic factors for OS (HR 1.860, P=0.0435 and HR 1.883, P=0.0233, respectively). The only independent poor prognostic factor for DSS was IL-6≥8pg/mL (HR 2.052, P=0.0329). Serum albumin was significantly lower and serum C-reactive protein and neutrophil-to-lymphocyte ratio were significantly higher in the IL-6≥8pg/mL group than in the IL-6<8pg/mL group (all P<0.0001). Preoperative serum IL-6 level is an independent poor prognostic factor for both OS and DSS after HNS-FTTR, reflecting the degree of preoperative systemic inflammatory response.

Sarcopenia is Associated With Oncological Prognosis and the Incidence of Secondary Cancer in Patients With Middle/Lower Rectal Cancer

ObjectiveThis study evaluated the clinical implications of sarcopenia for patients with rectal cancer according to cancer progression. Summary Background DataThe negative impact of body composition on long-term outcome has been demonstrated for various malignancies. MethodsWe retrospectively reviewed 708 patients with rectal cancer who underwent curative resection at our institution between 2003 and 2020. Factors contributing to long-term outcomes and the incidence of secondary cancer (ISC) were analyzed. Psoas muscle mass index (PMI) was assessed using preoperative computed tomography. Sarcopenia was defined using the PMI cut-off values for Asian adults (6.36 cm2/m2 for males and 3.92 cm2/m2 for females). ResultsSarcopenia was identified in 306 patients (43.2%). Sarcopenia was associated with advanced age, low body mass index, smoking history, and advanced T-stage. Multivariate analysis showed sarcopenia was an independent poor prognostic factor for OS (HR 1.71; P = .0102) and cancer-specific survival (HR 1.64; P = .0490). Patients with sarcopenia had significantly higher mortality due to cancer-related death in stages III and IV, whereas non-rectal cancer-related death, including secondary cancer, was markedly increased in stage 0-II sarcopenic rectal patients. Five-year cumulative ISC in patients with and without sarcopenia was 11.8% and 5.9%, respectively. Multivariate analysis revealed that sarcopenia was an independent predictive factor for ISC (HR 2.05; P = .0063). ConclusionsSarcopenia helps predict survival outcomes and cause of death according to cancer stage for patients with middle/lower rectal cancer who underwent radical surgery. Furthermore, sarcopenia increased the development of secondary cancer in those patients.

Ringed fluorodeoxyglucose uptake predicted poor prognosis after resection of pulmonary pleomorphic carcinoma

BackgroundPulmonary pleomorphic carcinoma (PPC) is a relatively rare and poorly differentiated non-small cell carcinoma. This study aimed to investigate the clinicopathological features including programmed cell death ligand 1 (PD-L1) expression status in patients with PPC who underwent curative resection.MethodsWe retrospectively studied 29 consecutive patients who had undergone anatomical lung resections for PPC. Perioperative and pathological variables, including radiological findings, were investigated to define prognostic factors.ResultsOverall survival (OS) rates were 71.8% at 1 year and 60.0% at 5 years. Disease-free survival (DFS) rates were 54.8% at 1 year and 43.6% at 5 years. Univariate analysis revealed that ringed fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) (p = 0.003), a cavity in the tumor on CT (p = 0.004), and tumor size (> 40 mm) (p = 0.014) were poor prognostic factors for OS. Regarding DFS, ringed FDG uptake (p = 0.002), a cavity on CT (p < 0.001), tumor size (p = 0.007), and pleural invasion (p = 0.014) were poor prognostic factors. PD-L1 expression was not a prognostic factor.ConclusionThis study showed for the first time that ringed FDG uptake on PET/CT is a poor prognostic factor of PPC. PD-L1 expression status was not related to the prognosis.Trial registration The study was approved by the Kobe City Medical Center General Hospital’s ethics board (No. 20112) on August 20, 2020.

Influence of sarcopenia, clinical data, and 2-[18F] FDG PET/CT in outcome prediction of patients with early-stage adenocarcinoma esophageal cancer.

To determine the prognostic value of sarcopenia measurements done on staging 2-[18F] FDG PET/CT together with metabolic activity of the tumor in patients with adenocarcinoma esophagogastric cancer with surgical treatment. Patients with early-stage, surgically treated esophageal adenocarcinoma and available pre-treatment 2-[18F] FDG PET/CT were included. The standard uptake value (SUV) and SUV normalized by lean body mass (SUL) were recorded. Skeletal muscle index (SMI) was measured at the L3 level on the CT component of the PET/CT. Sarcopenia was defined as SMI < 34.4cm2/m2 in women and < 45.4cm2/m2 in men. Of the included 145 patients. 30% were sarcopenic at baseline. On the univariable Cox proportional hazards analysis, ECOG, surgical T and N staging, lymphovascular invasion (LVI) positive lymph nodes, and sarcopenia were significant prognostic factors concerning RFS and OS. On multivariable Cox regression analysis, surgical N staging (p = 0.025) and sarcopenia (p = 0.022) remained significant poor prognostic factors for OS and RFS. Combining the clinical parameters with the imaging-derived nutritional evaluation of the patient but not metabolic parameters of the tumor showed improved predictive ability for OS and RFS. Combining the patients' imaging-derived sarcopenic status with standard clinical data, but not metabolic parameters, offered an overall improved prognostic value concerning OS and RFS.

Prognostic Impact and Clinicopathological Features of Multiple Colorectal Cancers and Extracolorectal Malignancies: A Nationwide Retrospective Study

Introduction: Multiple primary malignancies (MPMs) are likely to develop in patients with colorectal cancer (CRC); however, their prognoses are unclear. This study aims to investigate the prognostic impacts and clinicopathological features of multiple CRCs and extracolorectal malignancies (EMs) with CRC. Methods: We retrospectively evaluated a total of 22,628 patients with stage I–III CRC who underwent curative resection at 24 referral institutes in Japan between January 2004 and December 2012. MPMs were classified as synchronous CRCs (SCRCs), metachronous CRCs, synchronous EMs (SEMs), and metachronous EMs. Results: The presence of SCRCs (odds ratio 1.54, p < 0.001) was independently associated with SEMs in the multivariate analyses. SEMs were the strongest poor prognostic factor for OS (hazard ratio [HR] 2.21, p < 0.001) and RFS (HR 1.69, p < 0.001) compared with age, sex, and primary T and N factors. The incidence of stomach cancer was the highest in EMs, followed by lung, breast, and prostate cancers. Multiple CRCs were evenly distributed throughout the right-side colon to the rectum. Discussion/Conclusion: SEMs were a strong poor prognostic factor for patients with stage I–III CRC. Patients with CRC, particularly those with SCRCs, should be surveyed for SEMs, especially for stomach and lung cancers.

Prognostic value of PTEN in de novo diagnosed metastatic prostate cancer.

The purpose of our study is to investigate the prognostic value of phosphatase and tensin homolog on chromosome 10 (PTEN) expression in patients with de novo metastatic castration naïve prostate cancer (mCNPC). A total of 205 patients with mCNPC at Fudan University Shanghai Cancer Center (Shanghai, China) were retrospectively examined. Immunohistochemical staining of PTEN was performed on prostate biopsy samples of these patients. Associations among clinicopathological features, patient survival and PTEN protein expression were analyzed. PTEN loss occurred in 58 of 205 (28.3%) patients. Loss of PTEN was significantly correlated with high metastatic volume (P = 0.017). No association between PTEN expression and Gleason score was observed. Patients with PTEN loss had significantly shorter progression-free survival (PFS, P < 0.001) and overall survival (OS, P < 0.001) compared with patients with intact PTEN expression. Multivariate analysis showed that elevated alkaline phosphatase, high metastatic volume and PTEN loss were independent poor prognostic factors for PFS. The Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 and PTEN loss were independent poor prognostic factors for OS. The adjusted hazard ratio of PTEN loss for PFS and OS was 1.67 (95% confidence interval [CI]: 1.14–2.43, P = 0.008) and 1.95 (95% CI: 1.23–3.10, P = 0.005), respectively. PTEN loss was also significantly associated with shorter PFS (P = 0.025) and OS (P < 0.001) in patients with low-volume metastatic disease. Our data showed that PTEN loss is an independent predictor for shorter PFS and OS in patients with de novo mCNPC.

Role of Thermal Ablation in Colorectal Cancer Lung Metastases.

Simple SummaryFor a long time, surgery has been the only local treatment for pulmonary metastases. Percutaneous thermal ablation appeared in the early 2000s as a minimally invasive alternative technique to surgery for patients who were not eligible for surgery or wanted to preserve quality of life. In this review, we discuss the role of thermal ablation in the management of lung metastases of colorectal cancer, and present the main results of the literature concerning oncological outcomes (local tumor control, survival) based on 12 relevant original studies each involving a minimum of 50 patients, with a minimal follow-up of 12 months.Background: Consensus guidelines of the European Society for Medical Oncology (ESMO) (2016) provided recommendations for the management of lung metastases. Thermal ablation appears as a tool in the management of these secondary pulmonary lesions, in the same manner as surgical resection or stereotactic ablative radiotherapy (SABR). Methods: Indications, technical considerations, oncological outcomes such as survival (OS) or local control (LC), prognostic factors and complications of thermal ablation in colorectal cancer lung metastases were reviewed and put into perspective with results of surgery and SABR. Results: LC rates varied from 62 to 91%, with size of the metastasis (<2 cm), proximity to the bronchi or vessels, and size of ablation margins (>5 mm) as predictive factors of LC. Median OS varied between 33 and 68 months. Pulmonary free disease interval <12 months, positive carcinoembryonic antigen, absence of neoadjuvant chemotherapy and uncontrolled extra-pulmonary metastases were poor prognostic factors for OS. While chest drainage for less than 48 h was required in 13 to 47% of treatments, major complications were rare. Conclusions: Thermal ablation of a selected subpopulation of patients with colorectal cancer lung metastases is safe and can provide excellent LC and delay systemic chemotherapy.

Abstract PS6-52: Identification of Aurora kinase A as a biomarker for prognosis in obesity patients with early breast cancer

Abstract Background: Obesity is associated both with a higher risk of developing breast cancer, particularly in postmenopausal women, and with worse disease outcome for women of all ages. The molecular mechanisms that link obesity-breast cancer are complex and unclear. We hypothesized that overexpression of Aurora A was associated with poor survival in obesity breast cancer and related axis mechanism were involved.Methods: Fifty hundred and eighteen primary breast cancer specimens were collected from First Affiliated Hospital of China Medical University between January 2011 and November 2016. Our independent variable was BMI at baseline, categorized as overweight (BMI ≥ 25 kg/m2, as Obesity cohort), and normal (18.5 ≤ BMI &amp;lt; 25 kg/m2, as Non-obesity cohort). The Immunohistochemical (IHC) staining was performed with Aurora A, Survivin, MMP11, Cyclin B1 and Cathepsin L. Kaplan-Meier curve was used to analyze overall survival in our cohorts and TCGA-BRCA data (GSE3494). Log-rank test was used to calculate P value. PPI network analysis and MCODE model was used to analysis Aurora- altered signal pathway from GSE78958.Results: We validated Aurora A over expression using an independent cohort with a total of 517 breast carcinoma tissues (319 Non-Obesity patients and 198 Obesity Patients). The expression level of Aurora A-positive was significant higher in obesity breast carcinoma compared with non-obesity cancer carcinoma (χ2=9.79, P=0.002). In the immunohistochemistry assay, the results confirmed that the expression level of Aurora A-positive was significantly associated with hormone receptor status (68.4% vs 77.9%, P=0.015) and HER2 status (28.7% vs 17.9%, P=0.003). Aurora A-positive tumors had larger tumor size, though not statistically significant (78.1% vs. 71.1%, P=0.070). High Aurora A expression was remarkably and significantly associated with OS (8-year OS ratio: 69.5% vs 81.1%, OR=1.76, 95% CI:1.03~3.02, P=0.041) in Obesity Cohort. Interesting, higher expression of Aurora A was not associated with a shorter overall survival time among the Non-obesity breast cancer (8-year OS ratio:81.4% vs 85.8%, OR=1.40, 95% CI:0.79~2.45, P=0.229). As for RFS, the expression levels of Aurora A expression genes have no significance with RFS statistically in Non-Obesity patients. The in Aurora A low expression group was in high Aurora A expression in Non-Obesity Cohort ( 5-year RFS ratio:82.2% vs 83.2%, OR=1.29, 95% CI: 0.77~2.16, P=0.307). While 5-year RFS ratio in high Aurora A expression group of Aurora A were 71.3% was a little shorter than the 5-year RFS ratio in low Aurora A expression group (OR=1.58, 95% CI:0.96~2.57, P=0.072). Aurora A and Lymph node metastases were significantly poor prognostic factors for OS, and borderline significance was noted for high BMI. Kaplan-Meier survival analysis from TCGA database confirmed that the high Aurora A expression group had worse prognosis (HR=1.47, 95%CI:1.14-1.90, P=0.003). The KEGG pathway enrichment results were consistent with GO biological process term analysis, in which CCNB1 was enriched for upregulated Aurora A. In IHC correlation analyasis, Aurora A level on tumor cytoplasm had broad connections with Cyclin B1 (correlation coefficient = 0.227, P=0.001).Conclusions: Our finding demonstrate here for the first time that high expression of Aurora A was notably correlated with early recurrence and poor overall survival in obesity patients with early breast cancer. The Aurora A-Cyclin B1 axis could be a potential promising therapeutic target for cancer intervention and therapy. Keywords: Early breast cancer, obesity, Aurora A, Overall survival, Cyclin B1 Citation Format: Junnnan Xu, Tao Sun. Identification of Aurora kinase A as a biomarker for prognosis in obesity patients with early breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-52.

Clinical Analysis of 46 Cases of Multiple Myeloma with Extramedullary Disease

To investigate the effect of clinical baseline data on prognosis in patients with multiple myeloma (MM) complicated by extramedullary disease (EMD). The clinical data of 46 MM patients with EMD were retrospectively analyzed. The clinical data and survival prognosis of MM patients in primary EMD group and recurrent EMD group were analyzed. The classified baseline data were expressed by the number of cases (percentage), the χ2 test was used to compare the two classification data groups. The OS and PFS curves were drawn by multiplication positive limit method (Kaplan-Meier). Log-rank test was used for the univariate analysis of prognosis, and COX proportional risk regression model was used for the multiple factors of prognosis. β 2 microglobulin≥2.7 g/L, lactic dehydrogenase≥250 U/L, serum calcium≥2.75 mmol/L, plasma cells in bone marrow≥60% were the poor prognostic factors for PFS. Serum calcium≥2.75 mmol/L and the plasma cells in bone marrow≥60% were the poor prognostic factors for OS. Multivariate regression analysis enroling the statistically significant factors in univariate analysis baseline date in factors in showed that plasma cell level≥60% in bone marrow was independent poor prognostic factors for PFS, and serum calcium≥2.75 mmol/L was an independent poor prognostic factor for OS. The IgG type is the most common type of MM complicated by EMD. The remission depth of primary EMD group≥VGPR was lower than that of recurrent EMD group, and there was significant difference between the two groups (P<0.05), and the median OS time of patients with primary EMD group was shorter than that of patients with recurrent EMD group, the difference was statistically significant (P<0.05). The 3-year survival rates of primary EMD group and recurrent EMD group were 10.0% and 34%, respectively, there was no significant difference between the two groups (P>0.05). The 5-year survival rate was 0 and 20%, respectively, there was significant difference between the two groups (P<0.05). The remission depth of primary EMD group≥VGPR is lower than that of recurrent EMD group，and the OS time of patients in primary EMD group is shorter than that in recurrent EMD group. Bortezomib-based chemotherapy could not improve the prognosis of patients with primary EMD and recurrent EMD, and the prognosis of patients with primary EMD is even worse.

Clinical significance of skeletal muscle density and sarcopenia in patients with pancreatic cancer undergoing first-line chemotherapy: a retrospective observational study

BackgroundTo investigate the clinical impact of sarcopenia and skeletal muscle density (SMD) among patients with metastatic pancreatic adenocarcinoma who underwent palliative first line gemcitabine-based chemotherapy.MethodsA total of 330 patients treated with first line gemcitabine-based chemotherapy between January 2010 and March 2017 were included. CT scans before chemotherapy and after 8±2 weeks were evaluated. The L3 skeletal muscle index (SMI) was used to detect sarcopenia and calculated as the total area of the L3 skeletal muscle divided by the height-squared (cm2/m2). SMD was quantified as the mean muscle radiation attenuation of the muscle cross-sectional area across the L3 vertebral body level and was assessed between − 29 and + 150 Hounsfield units.ResultsA SMI to SMD comparison revealed a positive correlation (R2 = 0.058, P < 0.001). Compared with high SMD, the risks of low SMI were 1.516 (95% confidence interval [CI]: 1.164–1.973) among patients with low SMD. Kaplan–Meier analysis showed that the low SMD was related to poor overall survival (OS, median, 6.1 versus [vs.] 7.9 months, P = 0.010). Multivariate analysis using Cox regression showed that low SMI (hazard ratio [HR]: 1.35, 95% CI: 1.03–1.78, P = 0.032) and low SMD (HR: 1.45, 95% CI: 1.09–1.93, P = 0.011) were poor prognostic factors for OS, respectively. Co-presence of low SMI and low SMD had more powerful prognostic implication for OS (HR: 1.58, 95% CI: 1.12–2.23, P = 0.010). Grade 3 or higher toxicity of chemotherapy was more frequently observed in patients who have a low SMI (43% vs. 59%, P = 0.019) and low SMD (44% vs. 60%, P = 0.023). OS was not related to SMD status among patients who were chemotherapy responders (complete or partial responses). However, among non-responders (stable or progressive disease), low SMD groups had significantly poorer OS in comparison with high SMD groups (median, 5.6 vs 7.4 months, P = 0.006).ConclusionsSarcopenia and SMD status can be considered a prognostic factor in patients with metastatic pancreatic adenocarcinoma who received palliative first line gemcitabine-based chemotherapy. Severe chemotherapy toxicity occurred in the sarcopenia and low SMD groups. Our data suggest that a comprehensive assessment of skeletal muscle parameters may be more useful prognostic factors.

High FIB-4 Index Predicts Poor Prognosis in Alcoholic Drinkers with Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is one of the most aggressive cancer with a poor prognosis. Prediction of the prognosis is important to determine the treatment strategy. Alcohol consumption is a well-known major risk factor for liver fibrosis and HCC. FIB-4 index is a non-invasive and easily applicable indicator of liver fibrosis based on age, AST, ALT and platelets, which is a highly predictive risk factor for HCC. The aim of this study is to evaluate the association between preoperative FIB-4 index and prognosis in patients with HCC among alcohol drinkers. Methods: Consecutive 197 patients who underwent surgical resection of HCC between 2000 and 2018 were included. The cut off value of FIB-4 was determined by ROC analysis. We analyzed the relationship between clinicopathological variables including FIB-4 and survival after hepatectomy. Survival data were analyzed using the Log-rank test for univariate analysis and Cox proportional hazards for multivariate analysis. P value of < 0.05 was judged as significant. Results: A univariate analysis revealed that HCV positive (p=0.023), high preoperative ICG retention rate at 15 minutes (p=0.020), high AFP (p=0.030), high PIVKA-Ⅱ (p=0.005) and high FIB-4 index (≥2.6; p< 0.001) were significant poor prognostic factors for OS. FIB-4 index retained its significance on multivariate analysis for OS (HR 2.281, 95%CI 1.309-3.975) along with PIVKA-Ⅱ (p=0.0006). High FIB-4 index was also an independent prognostic factor for DFS (HR 1.772 95%CI 1.231-2.552). Conclusion: Preoperative high FIB-4 index is an independent prognostic factor for OS and DFS in resected HCC.

Prognostic significance of nutritional markers in metastatic gastric and esophageal adenocarcinoma.

BackgroundMalnutrition and sarcopenia are poor prognostic factors in many cancers. Studies in gastric and esophageal (GE) cancer have focused on curative intent patients. This study aims to evaluate the prognostic utility of malnutrition and sarcopenia in de novo metastatic GE adenocarcinoma.MethodsPatients with de novo metastatic GE adenocarcinoma seen at the Princess Margaret Cancer Centre from 2010 to 2016 with an available pre‐treatment abdominal computed tomography (CT) were included. Malnutrition was defined as nutritional risk index (NRI) <97.5. Skeletal muscle index (SMI) was measured at the L3 level (sarcopenia defined as SMI <34.4 cm2/m2 in women and <45.4 cm2/m2 in men). Patients receiving chemotherapy had NRI and SMI recalculated at the time of first restaging CT.ResultsOf 175 consecutive patients, 33% were malnourished and 39% were sarcopenic at baseline. Patients with pretreatment malnourishment had significantly shorter overall survival (OS; 5.8 vs. 10.9 months, p = 0.000475). Patients who became malnourished during chemotherapy had worse OS compared to those who maintained their nutrition (12.2 vs. 17.5 months p = 0.0484). On univariable analysis, ECOG (p < 0.001), number of metastatic sites (p = 0.029) and NRI (p < 0.001) were significant prognostic factors while BMI (p = 0.57) and sarcopenia (p = 0.19) were not. On multivariable analysis, ECOG (p < 0.001), baseline NRI (p = 0.025), and change in NRI during treatment (p < 0.001) were significant poor prognostic factors for OS.ConclusionsIn de novo metastatic GE adenocarcinoma patients, ECOG, pretreatment NRI and change in NRI were significant prognostic factors for OS while sarcopenia was not. Use of NRI at baseline and during treatment can provide useful prognostic information.

Neutrophil-lymphocyte ratio and nutritional status are clinically useful in predicting prognosis in colorectal cancer patients

Background: Neutrophil-lymphocyte ratio (NLR) and nutritional status may provide a prognostic value in colorectal cancer (CRC). Thus, aim of this study was to evaluate the prognostic value of nutritional status and NLR in CRC patients.Methods: A retrospective analysis was conducted in CRC patients. The independent variables were body mass index (BMI), weight loss (WL) and NLR. Logistic regression was used to estimate the odds chance of low NLR. Kaplan-Meier curves and Cox regression were used to evaluate the overall survival at 5 years old.Results: In the 148 patients evaluated, the most prevalent nutritional status was overweight/obesity (43.2%) and 27.0% had severe WL. Sixty-seven subjects (45.3%) had NLR ≥ 3 that was associated with the lower OS (P < 0.001). There was a higher OS for overweight/obese patients (P = 0.002) and a lower among subjects with severe WL (P = 0.009). The NLR ≥3 (HR: 3.639; 95% CI, 1.708–7.771) was an independent poor prognostic factor for OS. Patients without WL (HR: 0.367, 95% CI, 0.141–0.954) and classified as overweight/obesity (HR: 0.260; 95% CI, 0.106–0.639) presented better prognostic.Conclusion: NLR, WL, BMI assessments are promising prognostic indicators in the CRC.

Survival after Resection of Multiple Tumor Foci of Intrahepatic Cholangiocarcinoma

BackgroundMultiple tumor foci of intrahepatic cholangiocarcinoma (ICC) are often considered a contra-indication for resection. We sought to define long-term outcomes after resection of ICC in patients with multiple foci. MethodsPatients who underwent resection for ICC between 1990 and 2017 were identified from 12 major HPB centers. Outcomes of patients with solitary lesions, multiple lesions (ML), and oligometastases (OM) were compared. OM were defined as extrahepatic metastases spread to a single organ. ResultsOne thousand thirteen patients underwent resection of ICC. On final pathology, 185 patients (18.4%) had ML and 27 (2.7%) had OM. Median survival of patients with a solitary tumor was 43.2 months, while the median survival of patients with 2 tumors was 21.2 months; the median survival of patients with 3 or more tumors was 15.3 months (p < 0.001). Five-year survival was 43.3%, 28.0%, and 8.6%, respectively. The median survival of patients without OM was 37.8 months versus 14.9 months among patients with OM (p < 0.001); estimated 5-year survival was 39.3% and 10.6%, respectively. In multivariable analysis, the presence of two lesions was not an independent poor prognostic factor for OS (HR 1.19; 95%CI 0.90–1.57; p = 0.229). However, the presence of three or more tumors was an independent poor prognostic factor for OS (HR 1.97; 95%CI 1.48–2.64; p < 0.001). ConclusionResection of multiple liver tumors for patients with ICC did not preclude 5-year survival: in particular, estimated 5-year OS for resection of two tumors was 28.0%.

Comparison between S-1 monotherapy and S-1 plus cisplatin as postoperative chemotherapy after R0 resection for stage IV gastric cancer patients with oligometastasis: A multicenter retrospective study.

123 Background: Gastric cancer (GC) with liver metastasis (M1: HEP) and para-aortic lymph node metastasis (M1: LYM) is categorized as stage IV. Based on the retrospective reports, surgical resection is weakly recommended for oligo-metastasis (O-Meta), if resectable, in the Japanese GC Treatment Guidelines 2018. Whereas S-1 monotherapy as adjuvant chemotherapy after surgery for stage II/III GC and S-1 plus cisplatin (SP) as palliative chemotherapy for unresectable stage IV GC are standard treatments, there is no consensus about post-operative chemotherapy (Post-Cx) after R0 resection of stage IV GC with O-Meta. Methods: The criteria for this retrospective study were: 1) no prior treatment for GC, 2) R0 resection including O-Meta (HEP or LYM) at 20 institutions in the Stomach Cancer Group of the Japan Clinical Oncology Group between 2007 and 2012, 3) histological confirmation of adenocarcinoma for primary tumor and O-Meta (M1: HEP or LYM), 4) no other distant metastasis such as peritoneal metastasis. Results: A total of 110 patients were collected. Of the 94 eligible patients, 84 patients underwent gastrectomy followed by Post-Cx with S-1 (S-1 group: n = 55), SP (SP group: n = 22) or others (Others group: n = 7), and 10 patients did not receive post-Cx (non-Cx group). Median age for the S-1, SP, Others and non-Cx groups were 66, 60, 61, and 79 years old. Sites of oligo-metastasis (HEP/LYM) was 21/34, 9/13, 2/5, and 7/3 in the S-1, SP, Others and non-Cx groups. The 3- / 5-year overall and relapse free survival (OS and PFS) rates of all the patients were 45.6/31.4% and 24.5/21.3%, respectively. Median OS was 28.5 and 36.5 months in the S-1 and SP groups (HR 0.99; 95% CI 0.54-1.82, p = 0.986). In multivariate analysis, no Post-Cx, over 70 years old were identified as the independent poor prognostic factor for OS (p &lt; 0.05). Conclusions: R0 resection followed by Post-Cx for GC patients with O-Meta showed favorable survival, while there seems no additional benefit of cisplatin to S-1 alone.