Marker For Overall Survival Research Articles

Sentinel lymph node biopsy after neoadjuvant treatment of breast cancer using blue dye, radioisotope, and indocyanine green: Prospective cohort study

BackgroundThe breast cancer treatment paradigm has shifted to neoadjuvant treatment. There are many advantages to neoadjuvant treatment, such as tumor downsizing, in vivo tumor biology testing, treating micrometastasis, and achieving complete pathological response (a surrogate marker for overall survival). However, in the post neoadjuvant settings, sentinel lymph node biopsy can be done using a dual staining technique to decrease the false-negative rate (FNR) and increase the detection rate. However, many hospitals are not equipped to use radioisotopes. Here we investigate the detection rate and accuracy of sentinel lymph node biopsy in post neoadjuvant treatment breast cancer, comparing radioisotope, isosulfan blue, and indocyanine green (ICG) approaches. Material and methodsThis prospective study includes breast cancer patients (T2–4, N1–2) who had received neoadjuvant treatment. Carcinomas were confirmed by tissue pathology. Patients who had previous surgical biopsy or surgery involving the axillary regions, and those with a history of allergy to ICG, isosulfan blue, or radioisotope were excluded from the study. ResultThe study was done between July 1, 2019 to March 31, 2020. The mean age of participants was 53 years. Fourteen (60.87%) were post-menopause, two (8.7%) were perimenopause, and seven (30.43%) were premenopause. The clinical-stage distribution of the participants was: 2A (8.7%), 2B (34.78%), 3A (43.48%), and 3B (13.04%). The primary tumor size was 4.82 ± 2.73 cm. The lymph node size was 1.8 ± 0.96 cm. The detection rates at the individual level were 95.23% with ICG, 85.71% with isosulfan blue, and 85.71% with a radioisotope. The detection rate increased up to 100% when the ICG and blue dye methods were combined. The FNRs of sentinel lymph node biopsy at the individual level were: 10% using ICG, 30% using isosulfan blue, and 40% using radioisotope. At the lymph node level, the detection rates were 93.22% using ICG, 81.78% using isosulfan blue, and 53.87% using a radioisotope. The FNRs of sentinel lymph node biopsy at the lymph node level were 19.05% with ICG, 21.43% with isosulfan blue, and 18.03% with a radioisotope. However, the FNR was less than 10% when ICG, isosulfan blue, and a radioisotope were combined. ConclusionWe can perform sentinel lymph node biopsy by combining blue dye with ICG as an optional modality and achieve a comparable outcome with combine radioisotope in locally advanced breast cancer after neoadjuvant treatment.

Vulvar cancer subclassification by HPV and p53 status results in three clinically distinct subtypes

ObjectiveThere is great need for better risk stratification in vulvar squamous cell carcinoma (VSCC). Our aim was to define the prognostic significance of stratifying VSCC based on p16 and p53 immunohistochemistry (IHC) as surrogate markers for HPV and TP53 mutations. MethodsA large retrospective cohort of surgically treated women with primary VSCC was used. VSCC were classified into three subtypes: HPV-positive (HPVpos), HPV-negative/p53 mutant (HPVneg/p53mut), and HPV-negative/p53 wildtype (HPVneg/p53wt). Overall survival (OS), relative survival (RS), and recurrence-free period (RFP) were depicted using the Kaplan-Meier method and survival curves for relative survival; associations were studied using univariable and multivariable Cox proportional hazard models. ResultsOf the 413 VSCCs, 75 (18%) were HPVpos, 63 (15%) HPVneg/p53wt, and 275 (66%) HPVneg/p53mut VSCC. Patients with HPVneg/p53mut VSCC had worse OS and RS (HR 3.43, 95%CI 1.80–6.53, and relative excess risk (RER) of 4.02; 95%CI 1.48–10.90, respectively, and worse RFP (HR 3.76, 95%CI 2.02–7.00). HPVpos VSCC patients showed most favorable outcomes. In univariate analysis, the molecular subtype of VSCC was a prognostic marker for OS, RS and RFP (p = 0.003, p = 0.009, p < 0.001, respectively) and remained prognostic for RFP even after adjusting for known risk factors (p = 0.0002). ConclusionsStratification of VSCC by p16- and p53-IHC has potential to be used routinely in diagnostic pathology. It results in the identification of three clinically distinct subtypes and may be used to guide treatment and follow-up, and in stratifying patients in future clinical trials.

Chemoradiation-Related Lymphopenia and Its Association with Survival in Patients with Squamous Cell Carcinoma of the Anal Canal.

Although treatment-related lymphopenia (TRL) is common and associated with poorer survival in multiple solid malignancies, few data exist for anal cancer. We evaluated TRL and its association with survival in patients with anal cancer treated with chemoradiation (CRT). A retrospective analysis of 140 patients with nonmetastatic anal squamous cell carcinoma (SCC) treated with definitive CRT was performed. Total lymphocyte counts (TLC) at baseline and monthly intervals up to 12 months after initiating CRT were analyzed. Multivariable Cox regression analysis was performed to evaluate the association between overall survival (OS) and TRL, dichotomized by grade (G)4 TRL (<0.2k/μL) 2 months after initiating CRT. Kaplan-Meier and log-rank tests were used to compare OS between patients with versus without G4 TRL. Median time of follow-up was 55 months. Prior to CRT, 95% of patients had a normal TLC (>1k/μL). Two months after initiating CRT, there was a median of 71% reduction in TLC from baseline and 84% of patients had TRL: 11% G1, 31% G2, 34% G3, and 8% G4. On multivariable Cox model, G4 TRL at two months was associated with a 3.7-fold increased risk of death. On log-rank test, the 5-year OS rate was 32% in the cohort with G4 TRL versus 86% in the cohort without G4 TRL. TRL is common and may be another prognostic marker of OS in anal cancer patients treated with CRT. The association between TRL and OS suggests an important role of the host immunity in anal cancer outcomes. This is the first detailed report demonstrating that standard chemoradiation (CRT) commonly results in treatment-related lymphopenia (TRL), which may be associated with a poorer overall survival (OS) in patients with anal squamous cell carcinoma. The association between TRL and worse OS observed in this study supports the importance of host immunity in survival among patients with anal cancer. These findings encourage larger, prospective studies to further investigate TRL, its predictors, and its relationship with survival outcomes. Furthermore, the results of this study support ongoing efforts of clinical trials to investigate the potential role of immunotherapy in anal cancer.

103P Chemotherapy-induced neutropaenia as a marker for overall survival (OS) in non-small cell lung cancer (NSCLC) patients undergoing gemcitabine/carboplatin (GemCarbo) chemotherapy: A 9-year real-life data

103P Chemotherapy-induced neutropaenia as a marker for overall survival (OS) in non-small cell lung cancer (NSCLC) patients undergoing gemcitabine/carboplatin (GemCarbo) chemotherapy: A 9-year real-life data

Cancer-associated fibroblasts, matrix metalloproteinase-9 and lymphatic vessel density are associated with progression from adenocarcinoma in situ to invasive adenocarcinoma of the lung.

The present study aimed to investigate the roles of cancer-associated fibroblasts (CAFs), matrix metalloproteinase-9 (MMP-9) and lymphatic vessel density (LVD) during the progression from adenocarcinoma in situ (AIS) to invasive lung adenocarcinoma (IAC). A total of 77 patients with stage 0-IA lung adenocarcinoma were enrolled. The expression levels of α-smooth muscle actin, MMP-9 and D2-40 were immunohistochemically analyzed. Survival analysis was performed using the Kaplan-Meier method. In the non-invasive component, the proportion of CAFs and the expression levels of MMP-9 increased from AIS to IAC; however, the LVD was not significantly different. CAFs were positively correlated with levels of MMP-9. The LVD had no significant correlation with CAFs and MMP-9. In the invasive component, CAFs, MMP-9 and LVD were significantly higher in IAC compared with in minimally invasive adenocarcinoma. CAFs, MMP-9 and LVD were all positively correlated with each other. The micropapillary subtype in IAC was associated with overall survival (OS). The LVD in IAC, but not MMP-9 and CAFs, was associated with OS. CAFs, MMP-9 and LVD were involved in the progression from AIS to IAC. CAFs exhibited a strong association with MMP-9 levels in the non-invasive and invasive components. The increase in the proportion of CAFs and the expression levels of MMP-9 may have been an early event before the adenocarcinoma became invasive. Once the adenocarcinoma was invasive, the LVD served an important role in tumor invasion and metastasis, and hence may be used as a prognostic marker of poor OS in stage IA IAC.

Targetable ERBB2 mutation status is an independent marker of adverse prognosis in estrogen receptor positive, ERBB2 non-amplified primary lobular breast carcinoma: a retrospective in silico analysis of public datasets

BackgroundInvasive lobular carcinoma (ILC) accounts for 10–15% of primary breast cancers and is typically estrogen receptor alpha positive (ER+) and ERBB2 non-amplified. Somatic mutations in ERBB2/3 are emerging as a tractable mechanism underlying enhanced human epidermal growth factor 2 (HER2) activity. We tested the hypothesis that therapeutically targetable ERBB2/3 mutations in primary ILC of the breast associate with poor survival outcome in large public datasets.MethodsWe performed in silico comparison of ERBB2 non-amplified cases of ER+ stage I–III primary ILC (N = 279) and invasive ductal carcinoma (IDC, N = 1301) using METABRIC, TCGA, and MSK-IMPACT information. Activating mutations amenable to HER2-directed therapy with neratinib were identified using existing functional data from in vitro cell line and xenograft experiments. Multivariate analysis of 10-year overall survival (OS) with tumor size, grade, and lymph node status was performed using a Cox regression model. Differential gene expression analyses by ERBB2 mutation and amplification status was performed using weighted average differences and an in silico model of response to neratinib derived from breast cancer cell lines.ResultsILC tumors comprised 17.7% of all cases in the dataset but accounted for 47.1% of ERBB2-mutated cases. Mutations in ERBB2 were enriched in ILC vs. IDC cases (5.7%, N = 16 vs. 1.4%, N = 18, p < 0.0001) and clustered in the tyrosine kinase domain of HER2. ERBB3 mutations were not enriched in ILC (1.1%, N = 3 vs. 1.8%, N = 23; p = 0.604). Median OS for patients with ERBB2-mutant ILC tumors was 66 months vs. 211 months for ERBB2 wild-type (p = 0.0001), and 159 vs. 166 months (p = 0.733) for IDC tumors. Targetable ERBB2 mutational status was an independent prognostic marker of 10-year OS—but only in ILC (hazard ratio, HR = 3.7, 95% CI 1.2–11.0; p = 0.021). Findings were validated using a novel ERBB2 mutation gene enrichment score (HR for 10-year OS in ILC = 2.3, 95% CI 1.04–5.05; p = 0.040).ConclusionsTargetable ERBB2 mutations are enriched in primary ILC and their detection represents an actionable strategy with the potential to improve patient outcomes. Biomarker-led clinical trials of adjuvant HER-targeted therapy are warranted for patients with ERBB2-mutated primary ILC.

Low Myostatin Serum Levels Are Associated with Poor Outcome in Critically Ill Patients

Background: Growth differentiation factor 8, GDF-8 (Myostatin), is a protein released by myocytes inhibiting muscle growth and differentiation. Serum concentrations of Myostatin can predict poor survival in different chronic diseases, but its role in critical illness and sepsis is obscure. Our aim was to investigate Myostatin levels as a potential prognostic biomarker in critically ill patients with sepsis. Methods: We therefore measured Myostatin serum concentrations in 165 critically ill patients (106 with sepsis, 59 without sepsis) upon admission to the medical intensive care unit (ICU), in comparison to 14 healthy controls. Results: Myostatin levels were significantly decreased in ICU patients compared to controls but did not differ in patients with or without sepsis. However, Myostatin concentrations were significantly lower in patients requiring mechanical ventilation and indicated a trend towards dependency of intravenous vasopressors. Interestingly, we observed a negative correlation between Myostatin levels and markers of systemic inflammation. Strikingly, overall survival (OS) was significantly impaired in patients with low Myostatin levels in all critically ill patients. Low Myostatin levels at baseline turned out as an independent prognostic marker for OS in multivariate Cox-regression analysis (HR: 0.433, 95% CI: 0.211–0.889, p = 0.023). Conclusions: In summary, serum Myostatin concentrations are significantly decreased in critically ill patients and associated with disease severity. Low Myostatin levels also identify a subgroup of ICU patients that are more likely to face an unfavorable clinical outcome in terms of OS.

Prognostic Markers of Overall Survival in Cancer Patients Attending a Cachexia Support Service: An Evaluation of Clinically Assessed Physical Function, Malnutrition and Inflammatory Status

Background Cancer cachexia is a muscle-wasting syndrome that results in physical function impairments and decreased survival. While body weight and muscle mass loss predict survival, the prognostic significance of physical function in this population is unclear. Thus, we evaluated the association between physical function, and other routine measures, and overall survival (OS) in cancer patients attending a cachexia support service. Methods Physical function was clinically-assessed using the 30 s sit-to-stand test and handgrip strength. Six-month weight loss, the Patient-Generated Subjective Global Assessment (PG-SGA) total score, C-reactive protein (CRP), albumin, and quality of life were also evaluated. Results Records from 203 patients (age: 68.6 ± 11.6 years) were included. Handgrip strength did not predict OS. Sit-to-stand repetitions predicted OS in the single variable, but not the multivariable analysis. Multivariable results suggested higher PG-SGA total scores (HR: 1.04, 95% CI: 1.01–1.07), six-month weight loss (HR: 1.02, 95% CI: 1.004–1.04), and elevated CRP (HR: 1.004, 95% CI: 1.0004–1.01) predicted shorter OS. Higher albumin predicted longer OS (HR: 0.93, 95% CI: 0.90–0.97). Conclusion Six-month weight loss, the PG-SGA total score, CRP, and albumin independently predicted survival, while physical function did not. Functional impairments remain a hallmark of cancer cachexia and the benefit of their routine assessment warrants further exploration, especially in relation to patient quality of life.

Effect of core needle biopsy number on intraductal carcinoma of the prostate (IDC-P) diagnosis in patients with metastatic hormone-sensitive prostate cancer

The number of core needle biopsies in metastatic prostate cancer cases are sometimes reduced to avoid various complications. We analyzed whether core needle biopsy number influence IDC-P detection rate in patients with metastatic castration-sensitive prostate cancer (mHSPC). We retrospectively evaluated data from 150 patients diagnosed with mHSPC. Subjects were allocated to three groups according to the number of core biopsies performed: ≤ 5, 6-9, and ≥ 10. The study endpoints were the cancer-specific survival (CSS) and overall survival (OS) rates. For patients who underwent ≥ 10 core biopsies, a significant difference on CSS was detected between with or without IDC-P (P = 0.016). On the other hand, the difference decreased as the number of core biopsies became smaller (6-9; P = 0.322 and ≤ 5; P = 0.815). A similar trend was identified for the OS outcome. A significant difference on OS was also found between with or without IDC-P in patients who underwent ≥ 10 and 6-9 core needle biopsies (P = 0.0002 and 0.017, respectively), but not in those who underwent ≤ 5 core biopsies (P = 0.341). IDC-P served as a stronger prognostic marker for CSS and OS than did the other factors included in the multivariate analysis for patients had ≥ 10 core biopsies (P = 0.016, and P = 0.0014, respectively). Given the IDC-P detection and its value as a prognostic marker, we propose the performance of ≥ 10 core biopsy procedures in patients diagnosed with mHSPC to minimize the sampling error of the IDC-P.

Factors predicting survival in thick melanoma: Do all thick melanomas have the same prognosis?

BackgroundIt is unknown whether all thick melanomas share the same prognostic features. We present a large, multi-institutional study on thick melanoma, evaluating for factors prognostic of survival. MethodsWe queried the database of the Sentinel Lymph Node Working Group for patients with thick melanoma (>4 mm) who had a sentinel lymph node biopsy from 1993 to 2018. Clinicopathologic characteristics were correlated with overall survival. ResultsThere were 1,235 patients with a median follow-up of 28 months. Median thickness was 5.9 mm, with 713, 356, and 166 cases having a thickness of >4 to 6, >6 to 10, and >10 mm, respectively. Ulceration was seen in 51.2% of cases, while sentinel lymph node metastases were seen in 439 of 1,235 (35.5%) cases. For melanomas >4 to 6 mm, age, thickness, ulceration, lymphovascular invasion, and sentinel lymph node metastasis were correlated with overall survival (all P < .05), but for melanomas >6 to 10 mm, only sex and sentinel lymph node metastasis were prognostic of overall survival (both P < .05). For melanomas >10 mm, only sentinel lymph node metastasis predicted overall survival on multivariable analyses (P < .05). ConclusionPrognostic markers of overall survival for thick melanoma include thickness, ulceration, and sentinel lymph node metastasis, but also include other unique factors such as lymphovascular invasion. Moreover, certain prognostic markers for survival are associated with different subgroups of thick melanoma, which vary based on thickness group.

Nomogram based on pre-treatment inflammatory biomarkers predicting survival in patients with head and neck soft tissue sarcoma.

Systemic inflammatory biomarkers reflect level of inflammatory response, which have been suggested as prognostic factors in cancer patients. To estimate the prognostic value of inflammatory biomarkers in 149 patients with head and neck soft tissue sarcoma (HNSTS). Pre-treatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), neutrophil-platelet score (NPS) and Aarhus Composite Biomarker Score (ACBS) were analyzed for association with overall survival (OS) and progression-free survival (PFS). Nomograms were consisted of independent predictors for OS and PFS, and evaluated by calibration curve and concordance index (C-index). In multivariate analysis, LMR (HR = 0.42, 95% CI: 0.19-0.94, P= 0.035), ACBS (HR = 2.05, 95% CI: 1.02-4.12, P= 0.045) and AJCC stage were independent prognostic markers of OS. Moreover, high NLR (HR = 1.78, 95% CI: 1.07-2.94, P= 0.024) and advanced AJCC stage were independently related with worse PFS. Calibration curves reflected good discriminative ability of prognosis. The nomograms showed better accuracy of predicting OS (C-index: 0.748 vs. 0.690, P= 0.009) and PFS (C-index: 0.644 vs. 0.612, P= 0.028) than stage. Pre-treatment LMR, ACBS and AJCC stage were effective predictor of OS. The NLR and AJCC stage could independently predict PFS. The nomogram might act as a promising prognostic model for OS and PFS in HNSTS.

P-114 Cytokines as a prognostic marker of overall survival in pancreatic cancer: A meta-analysis and systematic review

Pancreatic cancer is an aggressive malignancy with a dismal 5-year survival rate of only 9%. Novel biomarkers are urgently needed to improve the survival outcomes of patients with this dreaded disease. Cytokines serve a key role in tumor development and metastasis in pancreatic cancer, with each cytokine demonstrating unique functionality in the tumor microenvironment. This systematic review and meta-analysis examined the role of cytokines in prognosticating overall survival (OS) of pancreatic cancer patients.

Prognostic potential of automated Ki67 evaluation in breast cancer: different hot spot definitions versus true global score

PurposeThe proliferation-associated biomarker Ki67 has potential utility in breast cancer, including aiding decisions based on prognosis, but has unacceptable inter- and intralaboratory variability. The aim of this study was to compare the prognostic potential for Ki67 hot spot scoring and global scoring using different digital image analysis (DIA) platforms.MethodsAn ER+/HER2− breast cancer cohort (n = 139) with whole slide images of sequential sections stained for hematoxylin–eosin, pancytokeratin and Ki67, was analyzed using two DIA platforms. For hot spot analysis virtual dual staining was applied, aligning pancytokeratin and Ki67 images and 22 hot spot algorithms with different features were designed. For global Ki67 scoring an automated QuPath algorithm was applied on Ki67-stained whole slide images. Clinicopathological data included overall survival (OS) and recurrence-free survival (RFS) along with PAM50 molecular subtypes.ResultsWe show significant variations in Ki67 hot spot scoring depending on number of included tumor cells, hot spot size, shape and location. The higher the number of scored tumor cells, the higher the reproducibility of Ki67 proliferation values. Hot spot scoring had greater prognostic potential for RFS in high versus low Ki67 subgroups (hazard ratio (HR) 6.88, CI 2.07–22.87, p = 0.002), compared to global scoring (HR 3.13, CI 1.41–6.96, p = 0.005). Regarding OS, global scoring (HR 7.46, CI 2.46–22.58, p < 0.001) was slightly better than hot spot scoring (HR 6.93, CI 1.61–29.91, p = 0.009). In adjusted multivariate analysis, only global scoring was an independent prognostic marker for both RFS and OS. In addition, global Ki67-based surrogate subtypes reached higher concordance with PAM50 molecular subtype for luminal A and B tumors (66.3% concordance rate, κ = 0.345), than using hot spot scoring (55.8% concordance rate, κ = 0.250).ConclusionsWe conclude that the automated global Ki67 scoring is feasible and shows clinical validity, which, however, needs to be confirmed in a larger cohort before clinical implementation.

Predictive Markers of First Line Pazopanib Treatment in Kidney Cancer

Real-world evidence from clinical practices is fundamental for understanding the efficacy and tolerability of medicinal products. Patients with renal cell cancer were studied to gain data not represented by analyses conducted on highly selected patients participating in clinical trials. Our goal was to retrospectively collect data from patients with advanced renal tumours treated with pazopanib (PZ) to investigate the efficacy, frequency of side effects, and searching for predictive markers. Eighty-one patients who had received PZ therapy as first-line treatment were retrospectively evaluated. Overall survival (OS), progression-free survival (PFS) were assessed as endpoints. Median PFS and OS were 11.8 months (95% CI: 8.8–22.4); and 30.2 months (95% CI: 20.3–41.7) respectively. Severe side effects were only encountered in 11 (14%) patients. The presence of liver metastasis shortened the median PFS (5.5 vs. 14.8 months, p = 0.003). Median PFS for patients with or without side effects was 25.6 vs. 7.3 months, respectively (p = 0.0001). Patients younger than 65 years had a median OS of 41.7 months vs. 25.2 months for those over 65 years of age (p = 0.008). According to our results absence of liver metastases, younger age (<65 years) and presence of side effects proved to be independent predictive markers of better PFS and OS.

Prognostic Value of Dual-Time-Point 18F-Fluorodeoxyglucose PET/CT in Metastatic Breast Cancer: An Exploratory Study of Quantitative Measures.

This study aimed to compare the prognostic value of quantitative measures of [18F]-fluorodeoxyglucose positron emission tomography with integrated computed tomography (FDG-PET/CT) for the response monitoring of patients with metastatic breast cancer (MBC). In this prospective study, 22 patients with biopsy-verified MBC diagnosed between 2011 and 2014 at Odense University Hospital (Denmark) were followed up until 2019. A dual-time-point FDG-PET/CT scan protocol (1 and 3 h) was applied at baseline, when MBC was diagnosed. Baseline characteristics and quantitative measures of maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), corrected SUVmean (cSUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and corrected TLG (cTLG) were collected. Survival time was analyzed using the Kaplan–Meier method and was regressed on MTV, TLG, and cTLG while adjusting for clinicopathological characteristics. Among the 22 patients included (median age: 59.5 years), 21 patients (95%) died within the follow-up period. Median survival time was 29.13 months (95% Confidence interval: 20.4–40 months). Multivariable Cox proportional hazards regression analyses of survival time showed no influence from the SUVmean, cSUVmean, or SUVmax, while increased values of MTV, TLG, and cTLG were significantly associated with slightly higher risk, with hazard ratios ranging between 1.0003 and 1.004 (p = 0.007 to p = 0.026). Changes from 1 to 3 h were insignificant for all PET measures in the regression model. In conclusion, MTV and TLG are potential prognostic markers for overall survival in MBC patients.

Advanced Biliary Tract Cancer Treated with Gemcitabine plus Cisplatin (GEMCIS) and Novel Inflammatory Markers.

It is known that chronic inflammation plays an important role in the etiopathogenesis of biliary tract carcinoma (BTC). In this study, we wanted to examine the effect of neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), and prognostic nutritional index (PNI) on survival in advanced BTC treated with gemcitabine plus cisplatin (GEMCIS) regimen. Forty-two patients with advanced BTC treated with GEMCIS regimen were included in the study. Measurements for NLR, dNLR and PNI were calculated with available formulas. NLR, dNLR, and PNI values were dichotomized based on receiver operating characteristic curve analysis (cut-off values 3.94, 2.66, and 46, respectively). Univariate and multivariate analyses were performed to identify prognostic factors for 6-month progression free survival (PFS) and overall survival (OS) using a Cox proportional hazards model. The mean PFS was 5.3 (median 5) months, and the mean OS was 10.7 (median 11) months. The pre-treatment increased NLR (≥ 3.94) value was prognostic for lower 6-month PFS and 12-month OS rates. dNLR was not found to be important for survival times. Low PNI (< 36) value was prognostic for lower 6-month PFS and 12-month OS rates. In the multivariate analysis, increased NLR value was determined as an independent prognostic factor for 6-month PFS. In patients with advanced BTC using GEMCIS as the first-line chemotherapy regimen, NLR and PNI can be used as prognostic inflammatory markers for 6-month PFS and 12-month OS.

Predictors of overall survival following extended radical resections for locally advanced and recurrent pelvic malignancies.

In an era of personalised medicine, there is an overwhelming effort for predicting patients who will benefit from extended radical resections for locally advanced pelvic malignancy. However, there is paucity of data on the effect of comorbidities and postoperative complications on long-term overall survival (OS). The aim of this study was to define predictors of 1-year and 5-year OS. Data were collected from prospective databases at two high-volume institutions specialising in beyond TME surgery for locally advanced and recurrent pelvic malignancies between 1990 and 2015. The primary outcome measures were 1-year and 5-year OS. A total of 646 consecutive extended radical resections were performed between 1990 and 2015. The majority were female patients (371, 57.4%) and the median age was 63 years (range 19-89 years). One-year OS, primary rectal adenocarcinoma had the best survival while recurrent colon cancer had the worse survival (p = 0.047). The 5-year OS between primary and recurrent cancers were 64.7% and 53%, respectively (p = 0.004). Poor independent prognostic markers for 5-year OS were increasing ASA score, cardiovascular disease, recurrent cancers, ovarian cancers, pulmonary embolus and acute respiratory distress syndrome. A positive survival benefit was demonstrated with preoperative radiotherapy (HR 0.55; 95% CI 0.4-0.75, p < 0.001). Patient comorbidities and specific complications can influence long-term survival following extended radical resections. This study highlights important predictors, enabling clinicians to better inform patients of the potential short- and long-term outcomes in the management of locally advanced and recurrent pelvic malignancy.

Real-world outcome with abiraterone low-dose plus prednisone in patients with mCRPC in a Brazilian Public Cancer Center.

e17563 Background: Abiraterone acetate (AA) is a potent selective and irreversible inhibitor of CYP17 used as standard treatment for metastatic Castration Resistant Prostate Cancer (mCRPC). In the pivotal trial COU-AA 301, AA 1000 mg/day plus prednisone increased overall survival after docetaxel in patients with mCRPC. A recent trial demonstrated not inferiority with respect to PSA metrics in the reduced dose of 250mg/day AA associated with dietary intake, which is described as AA low dose (AALD). The introduction of generic AA in the Brazilian Pharma Market and after the endorsement of AALD from international guidelines, the use of AA in limited resourced hospitals became feasible. Since december 2018 our institution has incorporated AALD in patients with mCRPC in first or second line therapy, always after chemotherapy with Docetaxel (either in the sensitive or castration scenario). Methods: We retrospectively reviewed 49 patients with mCRPC that received AALD after chemotherapy with Docetaxel from December 2018 to January 2019. The primary end point was PSA response rate (decrease of ≥ 50% in the PSA concentration from pretreatment PSA value). Univariable analysis were performed to explore association between clinical and pathological features. Results: After a median follow-up of 5 months, 25 patients (51%) had PSA response rate ≥ 50%. Median age was 69 years-old and most patients (73.5%) were ECOG 0 and 1. Despite good ECOG, the population had aggressive disease characteristics with 57.1% being ISUP 4 and 5 and 69.4% being clinical stage IV at initial diagnosis. Seventeen patients (34.7%) were exposed to AALD at first line and 32 patients (65.3%) in second line. It was observed that patients in the first line had better PSA response rate them those treated in the second line (70,6% vs 40,6%. p 0.04). Conclusions: Despite the premature data, this retrospective analyses shows PSA response rate in about 50% of patients treated with AALD in the overall population and about 70% in those treated in first line therapy. Serum PSA response rate is known as a surrogate marker for overall survival in those patients. The protocol will for more mature data. AALD might be an alternative dose for treating patients in institutions with limited resources.

Prognostic markers for overall survival and outcome to LuPSMA radionuclide treatment in patients with metastatic castration-resistant prostate cancer.

5548 Background: The aim of this international multicenter retrospective analysis was to identify prognostic markers for the clinical outcome in late-stage mCRPC patients treated with 177Lutetium-prostate-specific membrane antigen (LuPSMA) radionuclide treatment. Methods: Patients with progressive mCRPC treated with LuPSMA at six centers in Germany, USA, and Australia were considered for inclusion. Eligible patients had 24 predefined, pretherapeutic covariates (demographics, prior mCRPC treatments, and PSMA PET/CT derived parameters) and survival data available. Endpoints included overall survival (OS) and PSA progression-free survival (PSA-PFS). Covariates were tested using univariate and mulitvariate proportional hazards regression Cox models. Results: 267/414 (64%) patients met inclusion criteria and were analyzed. 113 patients participated in clinical trials (ACTRN12615000912583, NCT03042312), while 154 were enrolled in compassionate-access programs. After a median follow-up of 22.5 months, median OS was 13.0 months (95%CI 11.6-14.4); 83% of the patients died. Median PSA-PFS was 4.0 months (95%CI 3.2-4.7). In the multivariate analysis, factors associated with shorter OS were: shorter time since diagnosis of prostate cancer (HR=2.04; p=0.002), lower number of prior systemic therapies (≤3; HR=1.56; p=0.006), prior exposure to chemotherapy (HR=1.42; p=0.05), lower hemoglobin levels (HR=1.13; p=0.002), higher number of lesions (≥20: HR=1.53; p=0.009), multiple sites of metastases (bone/LN only vs. bone + LN; HR=1.39; p=0.03) and visceral involvement (M1c) (HR=1.45; p=0.01). Factors associated with longer PSA-PFS were: longer time since diagnosis of prostate cancer (HR=0.44; p&lt;0.001), higher hemoglobin levels (HR=0.32; p=0.03), presence of pelvic lymph nodes (LN) metastasis (N1) (HR=0.68; p=0.01), no distant lymph node metastases (M1a) (HR=0.66; p=0.01), no skeleton involvement (HR=0.44; p=0.01), no visceral metastases (M1c) (HR=0.51; p&lt;0.001), higher PSMA-positive tumor volume (HR=0.87; p=0.04), and higher SUVmean (HR=0.94; p=0.002). Conclusions: This retrospective analysis identified prognostic factors for survival and treatment response to LuPSMA. Along with the conventional risk factors in mCRPC, PSMA PET/CT can be a useful tool for stratifying patients and guide patient’s selection for LuPSMA radionuclide treatment.

Prognostic factors impacting survival in early HER2-positive breast cancer (BC): Results from a 1,142 patients database study.

e12561 Background: early systemic therapy has reduced recurrence and mortality from BC, especially among HER2+ subtype. Despite these advances, the difficulty of developing countries in incorporating new treatments, as well as the molecular and phenotypic profiles of HER2+ BC, are associated with the heterogeneity of treatment responses, leading to poor prognosis and outcomes. However, real-world data on prognostic factors for early HER2+ BC patients are scarce, especially in the Brazilian context. Therefore, this study aims to evaluate the influence of prognostic factors on disease-free survival (DFS) and overall survival (OS) in early HER2+ BC patients. Methods: this retrospective study identified early HER2+ BC (stage I to III with positive immunohistochemistry and in-situ hybridization) patients from Pérola Byington’s public hospital database (São Paulo, Brazil) diagnosed between January 2010 to March 2018. Patients were excluded if they were less than 18 years old, participated in clinical trials, presented metastatic disease de novo, concurrent malignancy, or inconsistent data. Multivariate Cox regression was used to evaluate prognostic factors for survival, and OS and DFS were estimated by Kaplan-Meier analyses. Results: of the 1,625 patients identified in the database, 1,142 women were included in the study. Of those, 40% were diagnosed with less than 50 years old. Among the included patients, 40.3% were HR-/HER2+ and 59.7% were HR+/HER2+. In addition, 19.4% of patients were diagnosed at stage I, 42.9% at stage II and 37.7% at stage III. A total of 1033 patients were included in the DFS analysis, with a probability of 71.8% DFS in 5-years. For OS analysis, a probability of 75.4% OS in 5-years was observed for 1139 patients included. The multivariate analysis showed that tumor staging, lymph node involvement and pathological complete response (pCR) were independent prognostic factors for both DFS and OS. Conclusions: the study in the Brazilian cohort corroborates the literature, showing that tumor staging, pCR, and lymph node involvement are key markers for DFS and OS and they should be considered when managing the early HER2+ BC patients. [Table: see text]