Factor For Poor Progression-free Survival Research Articles

Evaluating the Effectiveness of Cyclin-Dependent Kinase 4/6 Inhibitors in Early- and Very Early-Onset Metastatic Breast Cancer: A Multicenter Study.

Background and Objectives: Early-onset breast cancer (EOBC), particularly in patients under 40, presents with distinct biological characteristics and worse survival outcomes compared to late-onset cases. Despite intensive treatments, EOBC patients, especially those with hormone receptor-positive, HER2-negative (HR+/HER2-) subtypes, show poorer prognosis. CDK4/6 inhibitors, combined with endocrine therapy (ET) have become the standard for HR+/HER2- metastatic breast cancer, yet younger patients are underrepresented in clinical trials. This study aims to evaluate the efficacy of ribociclib and palbociclib with ET in HR+/HER2- metastatic breast cancer, addressing the critical gap in understanding treatment outcomes in younger patient populations. Materials and Methods: This multicenter, retrospective study evaluated the efficacy and safety of cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors, ribociclib, and palbociclib, in combination with endocrine therapy in patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer. Results: A total of 198 patients treated between 2019 and 2023 were analyzed for progression-free survival, overall survival, and prognostic factors. Very early-onset breast cancer, which is diagnosed before the age of 35, was identified as an independent prognostic factor for poor progression-free survival. Additional factors associated with poorer outcomes included liver metastasis, progesterone receptor negativity, high tumor grade, and the concurrent use of fulvestrant with CDK4/6 inhibitors. Both ribociclib and palbociclib demonstrated similar efficacy, and dose reductions due to treatment-related adverse events did not compromise therapeutic outcomes. Conclusions: This study is the first to focus specifically on the treatment of early-onset breast cancer with CDK4/6 inhibitors, providing critical insights into the unique challenges faced by this patient population. The findings underscore the urgent need for personalized treatment strategies, routine genetic testing, and dedicated clinical trials designed to address the specific needs of these high-risk subgroups. By advancing our understanding of the clinical and molecular landscape of early-onset breast cancer and very early-onset breast cancer, this study lays the groundwork for improving outcomes in these underserved patients through tailored therapeutic approaches.

Clinical Features and Prognosis Analysis of 168 Cases of MYC/BCL2 Double Expression Diffuse Large B Lymphoma

Objective: A retrospective study of the clinical features and prognosis of MYC/BCL2 double-expressor diffuse large B-cell lymphoma (DEL). Methods: A retrospective analysis was conducted on patients diagnosed with MYC/BCL2 double-expressor diffuse large B-cell lymphoma (DEL) for the first time by pathological and fluorescence in situ hybridization (FISH) techniques at Fujian Medical University Affiliated Union Hospital from January 2017 to December 2021. Clinical features, immunohistochemistry, laboratory tests, treatment plans, and follow-up information of all patients were collected. Kaplan-Meier analysis was used for univariate analysis, and Cox proportional hazards model was used for multivariate analysis. Results: Clinical characteristics:Among the 168 patients with diffuse large B-cell lymphoma (DLBCL), 13 cases (7.7%) involved the primary central nervous system. Of the patients, 95 (56.55%) were male and 73 (43.45%) were female, resulting in a male-to-female ratio of 1.3:1. The age of onset was at least 60 years for 93 cases (55.36%), with the youngest being 22 years old and the oldest being 88 years old. The median age was 62 years old. A total of 113 cases (72.90%) were classified as stage III-IV by the Ann Arbor staging system, 40 cases (23.81%) had B symptoms, 82 cases (52.90%) had an International Prognostic Index (IPI) score of 3-4, 84 cases (54.19%) had involvement of two or more extranodal sites, 87 cases (51.79%) had a β2-microglobulin (β2-MG) level of ≥2.53mg/L, 122 cases (72.62%) had a serum albumin (SA) level of <35g/L, and 103 cases (61.31%) had elevated levels of lactate dehydrogenase (LDH).Survival status: Complete follow-up data were available for 162 DEL patients, with a median follow-up time of 20.38 (1-73) months. The median overall survival (OS) was not reached, while the median progression-free survival (PFS) was 37.1 months. Among them, and 58 (34.5%) died. Survival analysis was performed on 168 DEL patients, with 1-year, 3-year, and 5-year OS rates of 82.1%, 61.1%, and 58.9%, respectively. The 1-year, 3-year, and 5-year PFS rates were 69.5%, 51.4%, and 45.6%, respectively. Among the 93 elderly (≥60 years old) DEL patients, the 1-year, 3-year, and 5-year OS rates were 77.2%, 52.7%, and 48.6%, respectively, and the 1-year, 3-year, and 5-year PFS rates were 67.4%, 47.4%, and 43.7%, respectively. The 1-year and 3-year OS rates of the 13 patients with primary central nervous system DLBCL were 25.50%, and the 1-year and 3-year PFS rates were 16.70%.Clinical efficacy analysis: Among 168 patients with DEL, the complete remission (CR) rate was 62.5% (105/168), the partial remission (PR) rate was 3.5% (6/168), the overall effective rate (ORR) was 66.1%, and the relapse/progression rate was 25.6% (43/168). Comparing the efficacy of 88 patients treated with the R-CHOP regimen with 32 patients treated with sildalafil combined with the R-CHOP regimen, the results showed a higher CR rate (81.25% vs. 67.05%) and a lower relapse rate (3.13% vs. 12.5%) in patients treated with sildalafil combined with the R-CHOP regimen.4. Univariate analysis: Age over 60 years ( P=0.031), B symptoms ( P=0.031), advanced Ann Arbor stage (P=0.003), high IPI score ( P<0.001), elevated LDH ( P=0.031), and elevated β2-MG( P<0.001) were significantly correlated with poor prognosis in DEL patients, and were identified as adverse prognostic factors. Non-GCB subtype ( P=0.029), B symptoms ( P<0.001), advanced Ann Arbor stage ( P<0.001), high IPI score ( P<0.001), decreased serum albumin ( P<0.001), elevated LDH (P=0.085), and elevated β2-MG(P<0.001) were significantly associated with poorer progression-free survival (PFS) among DEL patients.5.Multivariate analysis revealed that elevated β2-MG levels and high IPI scores were independent risk factors for poor overall survival (OS) in DEL patients, with HR values of 2.363 and 7.090, respectively. B symptoms, elevated β2-MG levels, and reduced serum albumin (SA) levels were independent risk factors for poor progression-free survival (PFS) in DEL patients, with HR values of 1.819, 2.879, and 1.987, respectively. Conclusion: Elevated β2-microglobulin and high IPI scores in DEL patients are risk factors for OS, while B symptoms, elevated β2-microglobulin, and decreased serum albumin are risk factors for PFS. Keywords: Lymphoma, diffuse large B-cell, clinical features, prognosis, double- expression lymphoma

375P The co-mutations and genetic features of BRAF-mutated gene mutations in a large Chinese MSS colorectal cancer cohort

BRAF p.V600E is a known prognostic factor for poor progression-free survival and overall survival in colorectal cancer (CRC), occurring in 5%-8% patients. This is a special population resistant to chemotherapies. A combined regimen of targeted drugs including MEK inhibitor, BRAF inhibitor and EGFR inhibitor is effective in BRAF V600E mutated patients, while it is only authorized as second-line treatment. BRAF V600E mutation was also considered correlated with sporadic MSI-H. However, studies on other alterations in the BRAF gene are few, and the differences of comprehensive genetic features between BRAF mutated and BRAF wild-type in microsatellite stable (MSS) CRC remain unclear.

Differential prognostic impact of complete blood count-related parameters by prior use of novel androgen receptor pathway inhibitors in docetaxel-treated castration-resistant prostate cancer patients.

There are multiple reports on the value of complete blood count (CBC)-related parameters on prognosis in docetaxel-treated castration-resistant prostate cancer (CRPC) patients before the emergence of androgen receptor pathway inhibitors (ARPIs). We investigated the prognostic significance of CBC-related parameters in docetaxel-treated CRPC patients. Patients treated with docetaxel chemotherapy for CRPC between 2008 and 2018 were included. We analyzed the relevance of CBC-related parameters to oncological prognosis in docetaxel chemotherapy, associated with prior use of novel ARPIs. Among 144 Japanese men treated with docetaxel, 49 men (34.0%) had already received ARPI therapy. A high neutrophil-lymphocyte ratio (NLR) was a prognostic factor for poor progression-free survival and overall survival (OS) in both univariate and multivariate analyses. In addition, a low hemoglobin (Hb) level and a high systemic immune-inflammation index (SII) were prognostic factors of poor OS in univariate analysis. Hb level was a prognostic factor of OS in both ARPI-naive and ARPI-treated patients. However, a high NLR and SII were only associated with a poor prognosis in ARPI-naive but not in ARPI-treated patients. Hb, NLR, and SII have been suggested to be prognosticators in docetaxel-treated CRPC patients. The differential prognostic value of NLR and SII between ARPI-naive and ARPI-treated patients may require caution when using these markers in docetaxel-treated CRPC patients.

Application value of plasma exosomal long RNA in SCLC diagnosis and prognosis.

8566 Background: Little research has focused on blood exosomal transcription profile in small cell lung cancer (SCLC). The aim of this study is to identify plasma exosomal specific transcriptional profile in SCLC and explore the application value of plasma exosomal long RNA (exLR) in SCLC diagnosis and prognosis. Methods: This study included 81 healthy people and 40 SCLC patients receiving standard first-line chemotherapy with etoposide and carboplatin/cisplatin. The efficacy was evaluated by progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR). 19 Patients who achieved complete response (CR) or partial response (PR) as best response during the first-line therapy and had not progressed within the following 90 days after the end of first-line therapy were defined as chemosensitive. 21 Patients who achieved stable disease (SD) as best response or received progressive disease during the first-line therapy or within the following 90 days after the end of first-line therapy were defined as chemoresistant. Baseline plasma samples were collected from 40 SCLC patients (17 patients’ samples after 2 courses were collected) and 81 healthy people. Plasma exosomes were isolated and purified; exosomal RNA were extracted for high-throughout sequencing analysis. Results: We obtained plasma exLRs profiles from 81 healthy control samples and 57 SCLC samples (baseline samples from 40 patients plus samples collected by 17 patients after 2 courses). Bioinformatics analysis found that exLRs were significantly different between the SCLC and the healthy control group; between the chemosensitive and the chemoresistant group; between the baseline samples and the paired samples after 2 courses. For 40 SCLC patients receiving first-line chemotherapy, ORR was 65.0%, DCR was 90.0% and mPFS was 6.0 months (95% CI, 4.3-7.7 months). Multivariate analysis showed that baseline brain metastases and baseline bone metastases were independent predictors of poor PFS; and 223 genes were independent predictors of PFS. There were 10 genes (AC107954.1, H2AFZP2, CALB2, IFITM9P, GFPT2, PLA1A, CHST10, AC021231.2, SETP20, HILPDA) intersected in differentially expressed genes between the SCLC and the healthy control group, differentially expressed genes between the chemosensitive and the chemoresistant group and independent predictors of PFS. These 10 genes were highly expressed in both the SCLC group and the chemoresistant group, and their high expression was an independent risk factor for poor PFS. Conclusions: This study firstly identified the plasma exLRs profiles in SCLC patients, verified the feasibility and value of identifying biomarkers based on exLRs profiles in SCLC diagnosis and prognosis.

Impact of time to relapse and response to salvage therapy on post autologous stem cell transplant outcomes in relapsed or refractory diffuse large B-cell lymphoma.

e19501 Background: The current standard of care for patients with relapsed or refractory (RR) diffuse large B-cell lymphoma (DLBCL) following frontline immunochemotherapy (IC) is salvage therapy, followed by high-dose chemotherapy and autologous stem cell transplant (ASCT) rescue in patients responding to salvage therapy. Time to first relapse (or refractory status) and response to salvage therapy in patients with RR DLBCL may reflect the chemosensitivity of the underlying disease. The aim of this study is to determine whether these factors impact post-ASCT outcomes. Methods: Patients with DLBCL that relapsed after R-CHOP or R-CHOP-like frontline therapy who underwent salvage therapy and ASCT at Mayo Clinic or University of Iowa between 07/2000 and 4/2020 were identified from institutional lymphoma and transplant databases. Clinical characteristics, treatment information, and outcome data were abstracted. Progression-free survival (PFS) and overall survival (OS) from the time of ASCT were analyzed using Kaplan-Meier method and Cox proportional hazards models. Results: A total of 437 patients with RR DLBCL who underwent salvage therapy and ASCT were identified. 280 (64%) were male. Median time from initial diagnosis to 1st relapse/salvage was 1.0 years (range 0.1-16.4). A median of 1 line (range 1-3) of salvage therapy was required. Response prior to ASCT was complete response (CR) in 211 (48%), partial response in 199 (46%), stable disease in 24 (5%), and unknown in 3 (1%) patients. Median age at ASCT was 61 years (range 19-78), and median follow up after ASCT was 8.0 years (95% CI 7.2-8.7). Median PFS and OS was 2.7 (95% CI 1.5-4.3) and 5.4 (4.2-7.4) years, respectively. Time to 1st relapse/salvage (≤1 vs 1-2 vs > 2 years) was not associated with PFS (median 0.8 vs 2.4 vs 4.9 years, p = 0.170) but was associated with OS (2.4 vs 7.4 vs 6.8 years, p = 0.013). Patients who required > 1 line of salvage therapy had significantly inferior PFS (median 0.3 vs 4.5 years, p < 0.001) and OS (0.9 vs 7.4 years, p < 0.001). In addition, patients who failed to achieve a CR prior to ASCT had significantly worse PFS (median 0.8 vs 5.3 years, p < 0.001) and OS (2.7 vs 9.2 years, p < 0.001). In multivariate Cox regression models adjusted for age and sex, time to 1st relapse/salvage was not associated with PFS (p = 0.313) or OS (p = 0.081); however, lines of salvage and response prior to ASCT remain significantly prognostic for PFS ( > 1 line of salvage: HR 2.14, 95% CI 1.59-2.87, p < 0.001; non-CR: HR 1.61, 95% CI 1.26-2.05, p < 0.001) and OS ( > 1 line of salvage: HR 2.25, 95% CI 1.66-3.05, p < 0.001; non-CR: HR 1.63, 95% CI 1.26-2.12, p < 0.001). Conclusions: In patients with RR DLBCL following frontline IC, requiring more than 1 line of salvage therapy and failure to achieve CR are strong independent risk factors for poor PFS and OS after ASCT. Novel therapies such as CAR-T cell therapy should be studied in this population.

Angiogenesis-related factors associated with nivolumab efficacy in patients with advanced gastric cancer after refractory or intolerant to ramucirumab-based therapy.

234 Background: Nivolumab (Nivo) is a standard therapy after ramucirumab (RAM)-based second-line chemotherapy in patients (pts) with advanced gastric cancer (AGC). However, the relationship between angiogenesis-related factors and the efficacies of immune-checkpoint inhibitors after anti-angiogenic chemotherapy is unclear. Methods: We retrospectively evaluated pts with AGCs who received Nivo after RAM-based second-line chemotherapy at a single institution from Nov 2017 to Aug 2019. Clinical benefit of Nivo was defined as CR, PR, or >4 months of SD and non-CR/non-PD. In addition, preserved serum samples at time points of pre-RAM, pre-Nivo, and post-Nivo (within 12 weeks from the start of Nivo) were analyzed by using the designated panel, containing vascular endothelial growth factor-A/D (VEGF-A/D), placental growth factor (PlGF), soluble vascular endothelial growth factor receptor-1/2/3 (sVEGFR-1/2/3), Interleukin-6/8 (IL-6/8), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), tissue inhibitor of metalloproteinase-1 (TIMP-1), angiopoietin-2, hepatocyte growth factor (HGF), interferon gamma (INF-γ), osteopontin (OPN), soluble neuropilin-1, and thrombospondin-2 (TSP-2). We investigated the association between angiogenesis-related factors and clinical outcomes with Nivo. Results: We evaluated 167 samples from 58 pts, including 10 pts (17.2%) exhibiting clinical benefit. Characteristics of pts were as follows: median age, 68; male, 74%; PS, 0/1-2, 17/83%; HER2 positive, 16%; prior gastrectomy, 40%; histology, intestinal/diffuse, 16/84%; disease status, metastatic/recurrent, 69/31%; lung metasstasis, 14%; liver metasstasis, 26%; peritoneum metastasis, 67%; lymph node metastasis, 31%. The median progression-free survival (PFS) and overall survival (OS) of Nivo were 1.7 and 6.2 months, respectively, with a median follow-up of 5.0 months. There were no correlations between pre-Nivo levels of angiogenesis-related factors and clinical benefit; however, the median post-Nivo/pre-Nivo VEGF-A ratio was significantly lower in pts with clinical benefit than in those without clinical benefit (0.44 versus 0.94, p = 0.008). By multivariate analysis using characteristics of pts and data from pre-Nivo samples, VEGF-A above the median level of 1400 pg/mL and sVCAM-1 below the median level of 1640000 pg/mL were independent prognostic factors for poor PFS (hazard ratio, 1.90, p = 0.033) and OS (hazard ratio, 2.02, p = 0.037), respectively. Conclusions: Our study suggests that rapid decline of serum VEGF-A level after Nivo and higher VEGF-A before Nivo were respectively associated with the clinical benefit of Nivo and poor survival in pts with AGC treated with Nivo after RAM-based second-line chemotherapy.

Microphthalmia-Associated Transcription Factor-Dependent Melanoma Cell Adhesion Molecule Activation Promotes Peritoneal Metastasis of Ovarian Cancer.

Ovarian cancer (OvCa) is one of the leading causes of death due to its high metastasis rate to the peritoneum. Recurrent peritoneal tumors also develop despite the use of conventional platinum-based chemotherapies. Therefore, it is still important to explore the factors associated with peritoneal metastasis, as these predict the prognosis of patients with OvCa. In this study, we investigated the function of microphthalmia-associated transcription factor (MITF), which contributes to the development of melanoma, in epithelial ovarian cancer (OvCa). High MITF expression was significantly associated with a poor prognosis in OvCa. Notably, MITF contributed to the motility and invasion of OvCa cells, and specifically with their peri-mesothelial migration. In addition, MITF-positive cells expressed the melanoma cell adhesion molecule (MCAM/CD146), which was initially identified as a marker of melanoma progression and metastasis, and MCAM expression was regulated by MITF. MCAM was also identified as a significant prognostic factor for poor progression-free survival in patients with OvCa. Collectively, our results suggest that MITF is a novel therapeutic target that potentially promotes peritoneal metastasis of OvCa.

The value of quantitative pentavalent 99mTc-dimercaptosuccinic acid scan in predicting progression-free survival and overall survival in patients with glioblastoma multiforme

AbstractAim:Glioblastoma multiforme (GBM) is the commonest and the most aggressive primary brain tumour. Pentavalent 99mTc-dimercaptosuccinic acid (99mTc (V)-DMSA) has been found to be a tumour-seeking agent. Pre-radiotherapy 99mTc (V)-DMSA positive scan was found to be significantly correlated with poor progression-free survival (PFS) and overall survival (OS). This study aims at evaluating the impact of quantitative 99mTc (V)-DMSA tumour uptake before and after radiotherapy on PFS and OS in patients with GBM.Methods:A prospective study included 40 patients with GBM. Single-photon emission computed tomography studies were done before and after adjuvant radiotherapy and were qualitatively and quantitatively evaluated. The retention index (RI) of the viable tumour was correlated with PFS and OS.Results:The qualitative enhancement of 99mTc (V)-DMSA uptake either positive or negative was significantly correlated with PFS at both early and late images (p-values 0·04 and 0·026, respectively) and OS only in the late image (p-value 0·036). The calculated ion/non-lesion ratios at late images were statistically correlated with PFS and OS (p-values 0·021 and 0·025, respectively). The baseline RI had significant correlation with PFS only (p-value 0·01).Conclusion:The degree of 99mTc (V)-DMSA scan positivity is a poor prognostic factor for PFS and OS in GBM patients.

Latest treatment strategies aiming for a cure in transplant-eligible multiple myeloma patients: how I cure younger MM patients with lower cost.

This article presents a practical overview of the treatment of younger, newly diagnosed multiple myeloma patients, focusing on novel treatment strategies. With the introduction of effective new agents, multiple myeloma is one of the most active and changing fields in clinical oncology. In addition, monitoring technology has become reliable and practical. Achieving and sustaining minimal residual disease negativity (MRD- ), such as multiparameter flow cytometry (MFC) < 10-5, is one of the goals of therapy. MRD- is significantly associated with prolonged progression-free survival, whereas MRD persistence (MRD +) is an independent factor for poor progression-free survival. Evidence from several recent studies evaluating modern therapy has further supported the positive correlation between depth of response and outcomes. Multiple myeloma can become a chronic illness with sustained MRD- in a significant number of patients. Our ultimate hope is to leverage tumoricidal-immunomodulatory sequential therapies and to cure a subset of our patients.

FGFR aberrations increase the risk of brain metastases and predict poor prognosis in metastatic breast cancer patients.

Background:The survival status of patients with breast cancer and brain metastasis (BCBM) receiving current treatments is poor.Method:We designed a real-world study to investigate using patients’ clinical and genetic aberrations to forecast the prognoses of BCBM patients. We recruited 146 BCBM patients and analyzed their clinical features to evaluate the overall survival (OS). For genetic testing, 30 BCBM and 165 non-brain-metastatic (BM) metastatic breast cancer (MBC) patients from Hunan Cancer Hospital, and 86 BCBM and 1416 non-BM MBC patients from the Geneplus database who received circulating tumor DNA testing, were compared and analyzed.Results:Ki67 >14% and >3 metastatic brain tumors were significant risk factors associated with poor OS, while chemotherapy and brain radiotherapy were beneficial factors for better OS. Compared with non-BM MBC patients, BCBM patients had more fibroblast growth factor receptor (FGFR) aberrations. The combination of FGFR, TP53 and FLT1 aberrations plus immunohistochemistry HER2-positive were associated with an increased risk of brain metastasis (AUC = 77.13%). FGFR aberration alone was not only a predictive factor (AUC = 67.90%), but also a significant risk factor for poor progression-free survival (Logrank p = 0.029). FGFR1 aberration was more frequent than other FGFR family genes in BCBM patients, and FGFR1 aberration was significantly higher in BCBM patients than non-BM MBC patients. Most FGFR1-amplified MBC patients progressed within 3 months of the late-line (>2 lines) treatment.Conclusion:A group of genetic events, including FGFR, TP53 and FLT1 genetic aberrations, and HER2-positivity, forecasted the occurrence of BM in breast cancers. FGFR genetic aberration alone predicted poor prognosis.

Abstract 3986: Digital droplet PCR measurement for plasma HER2 amplification in patients with AGC

Abstract Introduction: With the recent introduction of human epidermal growth factor receptor 2 (HER2) targeted therapies for patients with advanced gastric cancer (AGC), determining HER2 status is essential to select the patients who may benefit from this treatment. The current standard method assessing HER2 positivity is immunohistochemistry (IHC) or in situ hybridization assays, but this way of HER2 assessment has weaknesses especially when considering tumor heterogeneity. Using digital droplet polymerase chain reaction (ddPCR) technique, we evaluated HER2 amplification in both tissue and plasma samples collected from AGC patients and analyzed clinical implication of HER2 amplification in circulating tumor DNA. Method: Biopsied tissue and plasma samples were collected from patients with metastatic or recurrent AGC who were enrolled in AGC biomarker study conducted at Asan Medical Center. Samples were obtained before the start of anti-cancer treatment. HER2 amplification in DNA from tissue and cell-free DNA from plasma were determined by ddPCR, performed in Kindai University. Results: Samples of 63 patients with HER2 positive GC and 37 patients with HER2 negative GC enrolled between April 2014 and October 2017 were included in the analysis. As expected, the median HER2 copy number (CN) was higher in patients diagnosed as HER2 positive than negative, both for tissue (4.54 vs 0.95, P &amp;lt; 0.001) and plasma (1.49 vs 1.07, P &amp;lt; 0.001). ROC curve analysis showed 83.8% specificity and 69.8% sensitivity for tissue HER2 positivity at 1.17 CN of plasma HER2. In patients receiving anti-HER2 therapy (n=57), there was a trend for worse progression-free survival (PFS) outcome in patients with higher plasma HER2 CN (&amp;gt;1.5 vs ≤1.5), although no statistical significance was seen (median PFS 6.67 vs 8.19 months, P = 0.172). In multivariate Cox regression analysis including the age (&amp;gt;60 vs ≤60), HER2 IHC intensities (2+ vs 3+), and risk groups determined by Koo et al.’s prognostic model (Good vs Moderate vs Poor), higher plasma HER2 CN (&amp;gt;1.5 vs ≤1.5) was significantly associated with poor PFS (HR 2.22, 95% CI 1.14-4.32, P = 0.019). However, when tumor burden (sum of largest diameter of all measurable lesions) was combined as another factor in patients with measurable disease (n=39), plasma HER2 CN was no longer an independent factor (HR 1.38, 95% CI 0.58-3.27, P = 0.466) and larger tumor burden (&amp;gt;6.5cm vs ≤6.5cm) was found to be an independent prognostic factor for poor PFS (HR 2.63, 95% CI 1.12-6.21, P = 0.027), instead. Of note, plasma HER2 CN showed a positive relationship with tumor burden multiplied by tissue HER2 CN in linear regression (β=0.32, P = 0.002). Conclusion: Using the ddPCR technique, we found that plasma HER2 CN was significantly increased in HER2 positive GC patients compared to negative patients. However, plasma HER2 CN did not provide more information on predicting therapeutic effects than the tumor burden in patients receiving anti-HER2 therapy. Citation Format: Kyoungmin Lee, Kazuko Sakai, Min-Hee Ryu, Jae-Joon Kim, Young Soo Park, Young-Soon Na, Jungeun Ma, Hana Na, Kazuto Nishio, Yoon-Koo Kang. Digital droplet PCR measurement for plasma HER2 amplification in patients with AGC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3986.

Eukaryotic translation initiation factor 5A2 is highly expressed in prostate cancer and predicts poor prognosis.

Eukaryotic translation initiation factor (EIF) 5A2 exerts important functions that regulate the development and progression of cancers. The present study aimed to investigate the expression of EIF5A2 in prostate cancer (PCa) and its association with biological and prognostic significance. EIF5A2 mRNA and protein levels were analyzed in three paired samples of freshly resected PCa and adjacent non-tumor tissues. Immunohistochemical staining was used to detect the expression of EIF5A2 protein levels in 72 paraffin-embedded PCa tumor specimens. Subsequently, the association between EIF5A2 protein expression and clinicopathological parameters was assessed. Semi-quantitative reverse transcription-polymerase chain reaction and western blot analyses showed both EIF5A2 mRNA and protein levels were elevated in PCa compared with adjacent non-tumor tissues. Elevated EIF5A2 protein levels were observed in 73.6% (53/72) of the clinical PCa tissues using immunohistochemical staining. EIF5A2 expression was significantly associated with tumor stage (P=0.011) and biochemical recurrence status (P=0.032). Additionally, high levels of EIF5A2 predicted worse progression-free survival (P=0.007). Multivariate Cox regression analysis indicated that high expression of EIF5A2 was an independent prognostic factor for poor progression-free survival (hazard ratios, 0.366; 95% confidence interval, 0.349-0.460; P=0.021). The present study demonstrated that EIF5A2 is overexpressed in prostate cancer and may be a potential predictor and therapeutic target in PCa patients.

Pretreatment lymphocytopenia is an adverse prognostic biomarker in advanced-stage ovarian cancer.

The aim of this study was to investigate the prognostic significance of lymphocytopenia in advanced‐stage ovarian cancer. We retrospectively reviewed 506 patients with advanced‐stage ovarian cancer at Yonsei Cancer Hospital. This study included two cohorts of patients: a neoadjuvant chemotherapy (NAC) group (N = 247) and a primary debulking surgery (PDS) group (N = 259). The absolute lymphocyte count was recorded before treatment. A receiver operating characteristic (ROC) curve analysis was used to determine the cutoff for defining lymphocytopenia in the NAC cohort and followed by multivariate analysis. Subsequently, lymphocytopenia was assessed in the PDS cohort by multivariate analysis. A further analysis was performed to evaluate the absolute lymphocyte count as a continuous variable. An absolute lymphocyte count of 1.49 × 109/L was determined as the cutoff for the ROC curve analysis in the NAC cohort, and the multivariate analysis revealed that lymphocytopenia was an independent prognostic factor for poor progression‐free survival (PFS) [hazard ratio (HR), 1.50; 95% confidence interval (CI), 1.07‐2.11] and overall survival (OS) (HR, 2.02; 95% CI, 1.21‐3.40). In the PDS cohort, the multivariate analysis showed that lymphocytopenia was an independent prognostic factor for poor PFS (HR, 1.73; 95% CI, 1.20‐2.49) and OS (HR, 1.87; 95% CI, 1.27‐2.75). The absolute lymphocyte count was a significant factor when analyzed as a continuous variable in both the NAC and PDS cohorts. Pretreatment lymphocytopenia is an independent adverse prognostic factor in patients with advanced‐stage ovarian cancer.

Characterization of head and neck squamous cell carcinoma arising in young patients: Particular focus on molecular alteration and tumor immunity.

The purpose of this study was to comprehensively characterize head and neck squamous cell carcinoma (HNSCC) arising in young patients (<45 years old). We performed immunohistochemistry, silver, and fluorescence in situ hybridization using samples obtained from 396 radically resected cases among 1787 HNSCCs. Young age HNSCCs occurred in 10.9% (194/1787) and were most common in the oral tongue (50.5%). They revealed distinctively lower frequency of p16 positivity, high c-MET expression, MET copy number gain, and lower pan-Trk expression. PD-L1 positivity in tumor cells and ICOS+ tumor infiltrating lymphocytes (TILs) were higher in the young age. Perineural invasion, PD-L1 positivity, and higher ratio of CD163+ tumor infiltrating macrophages to CD8 + TILs were determined to be independent factors for poor progression-free survival. Characterizing these features of young age HNSCC may help to identify the underlying pathogenesis and to improve patient outcome through different treatment strategies.

Peritumoral Edema Affects the Prognosis in Adult Pleomorphic Xanthoastrocytoma: Retrospective Analysis of 25 Patients.

Pleomorphic xanthoastrocytoma (PXA) is a very rare glial neoplasm. The clinical behavior of PXA is not uniform, and the purpose of this study was to investigate the clinical characteristics of adult PXA and identify prognostic factors. Twenty-five patients aged 18 years or older who were diagnosed with PXA between 2002 and 2016 were analyzed. Twenty-one patients (84%) had PXA World Health Organization (WHO) grade II and 4 patients (16%) had anaplastic PXA (WHO grade III). The median overall survival of PXA WHO grade II and III was 97 and 56 months, respectively. The 3-year progression-free survival of PXA WHO grade II and III was 65.1% and 50%, respectively (P= 0.37 and 0.21). Diffusion-weighted imaging, perfusion-weighted imaging, and positron emission tomography findings failed to predict the histologic grade of PXA and recurrence of PXA WHO grade II. Tumor size >40 mm and presence of evident peritumoral edema (ePTE) were prognostic factors for poor progression-free survival (hazard ratios, 4.4 and 15.2, respectively; P=0.03 and 0.01) according to a univariate analysis. In the recurrent and silent PXA grade II groups, ePTE was present in 87.5% and 23.1% of cases, respectively (P <0.01). The clinical and radiologic features of PXA are not uniform. Tumor size and ePTE are possible prognostic factors for adult PXA. Also, peritumoral edema may be associated with recurrence in PXA WHO grade II. PXA showed a high recurrence rate, and thus close follow-up is needed.

PD-L1 in pancreatic ductal adenocarcinoma: a retrospective analysis of 373 Chinese patients using an in vitro diagnostic assay

BackgroundProgrammed death ligand 1 (PD-L1) has shown potential as a therapeutic target in numerous solid tumors. Its prognostic significance has also been established in pancreatic ductal adenocarcinoma (PDAC). The present study aimed to explore PD-L1 expression in PDAC cases in a large Chinese cohort using an in vitro diagnostic (IVD) assay to provide further insight into the potential value of programmed cell death protein 1 (PD-1) as a therapeutic target.MethodsThree hundred seventy-three PDAC patients were retrospectively recruited in this study. Tissue microarray (TMA) blocks were made from available formalin-fixed and paraffin-embedded (FFPE) tumor and matched adjacent tissue specimens. We evaluated PD-L1 protein expression via immunohistochemistry (IHC) using a U.S. Food and Drug Administration (FDA)-approved IVD assay. The relationships between PD-L1 positivity and both clinicopathological characteristics and patient prognosis were analyzed. PD-1 expression and clinicopathological significance were also evaluated.ResultsPD-L1 and PD-1 positivity were observed in 3.2% and 7.5% of cases, respectively. PD-L1 showed a predominantly membranous pattern in tumor cells, while no positive PD-L1 staining was observed in normal regions. Statistical analyses revealed that PD-L1 expression was associated with lymph node metastasis. PD-L1 positivity was a prognostic indicator of progression-free survival (PFS) and overall survival (OS) in univariate analyses, but only PFS remained statistically significant in multivariate analysis. PD-1 expression was detected in lymphocytes and was not associated with any clinicopathological feature except a history of pancreatitis.ConclusionsThe PD-L1 positivity rate is low in PDAC when evaluated using a companion diagnostic assay. It remains an independent prognostic factor for poor PFS.

Predictive Factors for Poor Progression-free Survival in Patients with Non-small Cell Lung Cancer Treated with Nivolumab.

Nivolumab has shown promising effects in patients with non-small-cell lung cancer (NSCLC) as a second- or later-line treatment. This study aimed to identify patients who would not experience any benefit from nivolumab treatment. In this study, data for 201 patients treated with nivolumab during 17 December 2015 to 31 July 2016 at three respiratory medical centers in Japan were retrospectively reviewed. We collected clinical data at the time of nivolumab treatment commencement. We investigated the relationship between progression-free survival (PFS) and patient characteristics. In both univariate and multivariate analysis, performance status (PS) score ≥2, steroid use at baseline and lactate dehydrogenase (LDH) level >240 IU/l were significantly associated with poor PFS (all p<0.05). PS score ≥2, steroid use at baseline and a high LDH level were predictive of poor PFS in patients with NSCLC treated with nivolumab. Careful monitoring is recommended for treating such patients with nivolumab (UMIN-ID: UMIN000025908).

1162P - Predictive factors for poor progression-free survival in patients with non-small-cell lung cancer treated with nivolumab

1162P - Predictive factors for poor progression-free survival in patients with non-small-cell lung cancer treated with nivolumab

Identification of a predictive factor of metastatic castration-resistant prostate cancer patients’ response to alternative antiandrogen therapy with flutamide.

321 Background: Recently, new androgen pathway inhibitors, abiraterone and enzalutamide, are demonstrated to improve overall survival for metastatic castration-resistant prostate cancer (mCRPC). In Japan, alternative antiandrogen (AA) as second-line hormonal therapy for mCRPC that relapses after initial hormone therapy have been commonly used before new androgen pathway inhibitors. In this study, we attempted to identify the predictive factors for efficacy of AA as second-line hormone therapy. Methods: We identified consecutive 65 mCRPC patients treated with AA as second-line hormonal therapy. All patients were treated with maximum androgen blockade (MAB) initially and evaluated antiandrogen withdrawal syndrome after relapse. We analyzed the correlations between progression-free survival (PFS) of AA and clinicopathological characteristics, including patients’ age, initial PSA levels, PSA levels at flutamide induction, Gleason scores, T stage, N stage, extent of disease (EOD) classifications on bone scan, and the previous duration of prostate cancer sensitivity to MAB. Results: The median duration of prostate cancer sensitivity to MAB was 11.3 months (range: 1.5-53.0 months). In multivariate analysis, four significant risk factors for poor PFS were identified; initial PSA levels ( &gt; 263 ng/mL vs ≤ 263; HR 0.53, p = 0.038), N stage (1 vs 0; HR 3.00, p = 0.001), EOD classifications (3-4 vs 1-2; HR 2.50, p = 0.007), and the previous duration of prostate cancer sensitivity to MAB ( &lt; 12 months vs ≥ 12; HR 2.16, p = 0.026). We stratified the patients into two cohorts with low risk (0-2 risk factor present) and high risk (3-4 risk factors present). We found a significant difference in PFS among risk groups (median PFS 7.3 months vs 1.5, p &lt; 0.000). Conclusions: Initial PSA, N stage, EOD classifications on bone scan, and the previous duration of prostate cancer sensitivity to MAB were the significant predictive factors for efficacy of AA as second-line hormone therapy in patients with mCRPC. These findings might support that decision-making of when to start the new AR pathway inhibitors.