ASO Visual Abstract: Radiologic and Pathologic Response as Predictors of Survival in Patients with Colorectal Peritoneal Metastases Undergoing Neoadjuvant Chemotherapy Followed by CRS-HIPEC: A Retrospective Study.

Background: Role of tumor-stroma ratio (TSR) as a predictor of survival in patients with non-small cell lung cancer (NSCLC) remains not clear. A systematic review and meta-analysis was conducted to summarize current evidence for the role of TSR in NSCLC.Methods: Relevant cohort studies were retrieved via search of Medline, Embase, and Web of Science databases. The data was combined with a random-effect model by incorporating the between-study heterogeneity. Specifically, subgroup and meta-regression analyses were performed to explore the association between TSR and survival in patients with squamous cell carcinoma (SCC) or adenocarcinoma (AC).Results: Nine cohort studies with 2031 patients with NSCLC were eligible for the meta-analysis. Pooled results showed that compared to those stroma-poor tumor, patients with stroma rich NSCLC were associated with worse recurrence-free survival (RFS, hazard ratio [HR] = 1.52, 95% confidence interval [CI]: 1.07 to 2.16, p = 0.02) and overall survival (OS, HR = 1.48, 95% CI: 1.20 to 1.82, p < 0.001). Subgroup analyses showed that stroma-rich tumor may be associated with a worse survival of SCC (HR = 1.89 and 1.47 for PFS and OS), but a possibly favorable survival of AC (HR = 0.28 and 0.69 for PFS and OS). Results of meta-regression analysis also showed that higher proportion of patients with SCC was correlated with higher HRs for RFS (Coefficient = 0.012, p = 0.03) and OS (Coefficient = 0.014, p = 0.02) in the included patients, while higher proportion of patients with AC was correlated with lower HRs for RFS (Coefficient = −0.012, p = 0.03) and OS (Coefficient = −0.013, p = 0.04), respectively.Conclusion: Tumor TSR could be used as a predictor of survival in patients with NSCLC. The relative proportion of patients with SCC/AC in the included NSCLC patients may be an important determinant for the association between TSR and survival in NSCLC. Stroma richness may be a predictor of poor survival in patients with lung SCC, but a predictor of better survival in patients with lung AC.

e15687 Background: Ki67 index is a predictor of survival in patients with metastatic neuroendocrine tumor (NET). The purpose of this study is to evaluate Ki67 index and other potential predictors of overall survival (OS) in patients with NET metastases to the liver treated with Y90 radioembolization. Methods: In an institutional review board-approved retrospective study, consecutive patients with NET metastases to the liver who were treated with Y90 radioembolization from 2013-2018 at a single institution were evaluated. Patients with documented Ki67 index were stratified according to 2017 World Health Organization (WHO) grading based on Ki67 index (G1: &lt; 3%, G2: 3-20%, G3: &gt; 20%). Age, gender, and objective tumor response on post Y90 imaging were also evaluated as potential predictors of survival after Y90. Objective tumor response was evaluated at 1 and/or 3 months post Y90 with multiphase MRI utilizing Response Evaluation Criteria for Solid Tumors (RECIST). Overall survival (OS) from time of Y90 was analyzed using Kaplan-Meier estimation. Predictors of survival were evaluated using log-rank test with p &lt; 0.05 as the statistically significant level. SPSS software v. 25 (IBM Corporation, Armonk, NY) was used for all statistical analysis. Results: A total of 77 patients were identified; 36 (47%) had a documented Ki67 index from either their primary tumor, liver metastasis, or both. Primary tumor site included pancreatic (n = 10), small bowel (n = 7), pulmonary (n = 5), gastric (n = 3), large bowel (n = 3), and renal (n = 1). A primary site was not identified in several patients (n = 7).G1 tumors comprised 31% (n = 11) of patients, while G2 and G3 tumors made up 50% (n = 18) and 19% (n = 7) of the cohort, respectively. Median overall survival (OS) of the entire cohort was 51.1 months. Median OS in patients was 63.0 months in G1 tumors, 51.1 months in G2 tumors, and 3.1 months in G3 tumors (p &lt; 0.001). Objective response on initial MRI follow-up after Y90 radioembolization also predicted prolonged OS (51.2 months versus 17.9 months, p &lt; 0.001). Age at time of diagnosis and gender were not predictors of survival after Y90 radioembolization. Conclusions: WHO grading based on KI67 index and objective tumor response appear to be predictors of prolonged survival in patients with metastatic NET to the liver treated with Y90 radioembolization.

INTRODUCTION In breast cancer (BC) patients, achieving a complete pathological response (pCR) after neoadjuvant chemotherapy (NCT) is associated with better prognosis. Despite this, some of these patients will experience recurrences of the disease and will eventually die of BC. We identified clinical factors that can affect recurrence and survival in BC patients who achieve pCR.METHODSRetrospective analysis of a Chilean BC database including patients treated in public and private hospitals in Santiago, Chile from 2010 to 2019. pCR was defined as the absence of residual invasive disease in the breast and in the axillary lymph nodes (ypT0/is N0) at the completion of the NCT. Invasive Disease-Free Survival (IDFS), Distant Disease-Free Survival (DDFS) and BC-specific survival (BCS) was measured from the time of diagnosis to the event or lost to follow-up. We performed Cox regression analysis to identify factors associated with prognosis.RESULTSFrom 855 patients who received NCT, 195 (22.8%) achieved pCR and were included in this study. Clinical characteristics are shown in table 1. 76 (37.9%) patients had hormone receptor positive (HR+) and 113 (57.4%) had Human epidermal growth factor 2 (HER2) positive tumors. 88.7% were treated with a regimen that included anthracyclines and taxanes. With a median follow-up of 36 months, three-year IDFS, DDFS and BCS and their 95% confidence intervals were 90.9% (84.7 - 94.6), 91.8% (86.0 - 95.3) and 93.8% (87.8 - 97.5); respectively. The stage at diagnosis was the only predictor associated with IDFS (Hazard ratio (HR) = 5.6; p = 0.02), DDFS (HR = 4.1, p = 0.07), and BCS (HR = 8.3, p = 0.04). Body mass index (BMI), age, hospital, HR or HER2 status, lymph node involvement, or the presence of an in-situ component, were not associated with prognosis in the multivariate analysis.CONCLUSIONThe clinical stage at diagnosis was the only predictor of survival in patients who achieved pCR after NCT. Short follow-up and few events may have affected these results. This data is consistent with previously published work. Table 1. Tumor and patient characteristicsMedian age49 (24 – 78)HospitalPublic57.4%Private43.6%BMIMedian27.2 (18.5 – 44.7)Overweight38.0%Obese31.9%Receptor StatusRH+/HER2-16.4%RH+/HER2+21.5%RH-/HER2+35.9%RH-/HER2-26.2%Clinical StageI2.1%II47.4%III50.5%Lymph Node +69.7%ypT0/N078.1%ChemotherapyAnthracycline5.1%Taxane6.2%Anthracycline-Taxane88.7% Citation Format: Francisco Acevedo, Benjamin Walbaum, Tomas Merino, Militza Petric, Cesar Sanchez. Clinical stage is the only predictor of survival in breast cancer patients with a complete pathological response [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 PS6-37.

Peritoneal metastases from colorectal cancer (pmCRC) are associated with poor prognosis. Neoadjuvant chemotherapy followed by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has improved survival in these patients. However, few studies have evaluated the influence of radiological and pathological responses on overall survival (OS) and recurrence-free survival (RFS) in this population. The objective of this study was to assess these prognostic markers in patients with pmCRC who received neoadjuvant chemotherapy followed by CRS-HIPEC at our institution. A total of 121 patients with pmCRC treated with neoadjuvant chemotherapy followed by CRS-HIPEC from 2012 to 2023 were included. Demographic, clinical, and oncological data were extracted from medical records. OS and RFS were obtained using Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses were done. After a median follow-up of 44.6 months, median OS was 47.1 months (95% confidence interval [CI] 32.4-61.6) and RFS was 21.8 months (95% CI 13.7-29.9). No significant difference in OS was observed among patients who achieved a partial response on imaging compared with non-responders (hazard ratio [HR] 0.9; 95% CI 0.5-1.5; p = 0.725). Patients who did not achieve a complete pathological response showed a significant difference in OS, with worse OS (HR 3.4; 95% CI 1.3-8.9; p = 0.012). OS was significantly lower in patients with a peritoneal carcinomatosis index >15 (HR 4.1; 95% CI 1.1-15; p = 0.033). Radiological response after neoadjuvant chemotherapy does not significantly affect the OS or RFS of patients with pmCRC. Complete pathological response is a significant prognostic marker for both OS and RFS.

Systemic and local inflammations have been described as relevant prognostic factors in patients with cancer. However, parameters that stand for immune activity in the pleural space have not been tested as predictors of survival in patients with malignant pleural effusion. The objective of this study was to evaluate pleural lymphocytes and Adenosine Deaminase (ADA) as predictors of survival in patients with recurrent malignant pleural effusion. Retrospective cohort study includes patients who underwent pleurodesis for malignant pleural effusion in a tertiary center. Pleural fluid protein concentration, lactate dehydrogenase, glucose, oncotic cytology, cell count, and ADA were collected before pleurodesis and analyzed. Survival analysis was performed considering pleurodesis as time origin, and death as the event. Backwards stepwise Cox regression was used to find predictors of survival. 156 patients (out of 196 potentially eligible) were included in this study. Most were female (72%) and breast cancer was the most common underlying malignancy (53%). Pleural fluid ADA level was stratified as low (<15U/L), normal (15≤ADA<40), and high (≥40). Low and high ADA levels were associated with worse survival when compared to normal ADA (logrank: 0.0024). In multivariable analysis, abnormal ADA (<15 or ADA≥40) and underlying malignancies different from lymphoma, lung, or breast cancer were associated with worse survival. Pleural fluid cell count and lymphocytes number and percentage did not correlate with survival. Pleural fluid Adenosine Deaminase levels (<15 or ≥40U/L) and neoplasms other than lung, breast, or lymphoma are independent predictors of worse survival in patients with malignant pleural effusion who undergo pleurodesis.

Predictors of Survival in Patients with Chronic Obstructive Pulmonary Disease Treated with Long-term Oxygen Therapy

Bioelectrical impedance phase angle is a potentially sensible indicator of alterations in body composition due to malnutrition, frequent in advanced cancer patients. Malnutrition is characterized by changes in cellular membrane integrity and alterations in fluid balance leading to alterations in body composition. Aim of this study was to investigate the role of phase angle as a predictor of survival in patients with advanced cancer. Twenty patients (12 males, 8 females: age 50.2 ± 3.2 years, weight 51.9 ± 7.1 kg; BMI 19.8 ± 1.8 kg/m2), with advanced cancer were evaluated. Single-frequency BIA was carried out and the BIA variables, resistance (R), reactance (Xc) and phase angle (PhA), were measured. Some anthropometric and biochemical parameters were performed in all patients. Phase angle resulted strictly related (p <0.001) with survival time, slightly (p = 0.055) related with lymphocyte count, but not related with the other anthropometric and biochemical parameters evaluated. Identification of a predictor of survival in advanced cancer patients is important to improve the therapeutic programme for the disease. Phase angle seems to have a role as a marker of morbidity and mortality in a wide range of disease conditions. Similar studies on larger sample sizes are needed to further validate the prognostic significance of phase angle in advanced cancer patients.KeywordsBIAphase anglecancertime survivalmalnutrition

Predictors of survival in prostate cancer patients with bone metastasis and extremely high prostate-specific antigen levels

EV are predictors of survival in patients with compensated cirrhosis. Beta-blockers (BB) are used in the prevention of variceal hemorrhage. Recent retrospective evidence suggests that BB may be associated with a poorer survival in patients with refractory ascites (Serste et al., Hepatology 2010). However, this may be due to the indication for BB use (i.e. presence of EV) rather than to BB use itself. The aim of the study was to investigate the prognostic relevance of EV in patients with decompensated cirrhosis, with ascites but without variceal hemorrhage. Methods: Retrospective cohort study of 729 consecutive patients with cirrhosis who underwent gastroscopic and hemodynamic evaluation, including hepatic venous pressure gradient (HVPG) measurement, in the period between 11/1995 and 11/2004 and who were followed until death or 11/2006. Results: 194 patients with decompensated cirrhosis (Child-Pugh score [mean±SD] 9.4±1.8; MELD 17.1±7.2; HVPG 16.9±5.3 mmHg) with ascites but without variceal hemorrhage were included in the study and followed for a mean of 37.3±36.2 months. Sixty-two patients had no EV and 132 had EV (63 small, 46 medium and 23 large). Patients with EV had a significantly poorer survival compared to those without EV (Figure). Multivariate analysis including Child-Pugh and MELD scores, HVPG, and EV revealed Child-Pugh score (HR [95%CI]: 1.18 [1.07–1.29]; p=0.001) and EV (1.18 [1.03–1.34]) as independent predictors of survival. Survival curves according to treatment with BB were not significantly different (p=0.7). Conclusion: Esophageal varices are independent predictors of survival in decompensated patients with ascites even in the absence of variceal hemorrhage. These results suggest that EV should be used to further stratify patients with decompensated cirrhosis. Treatment with BB in patients with ascites does not increase mortality.

To assess whether human papillomavirus (HPV) DNA detection in cervical cancer specimens, or antibodies to selected HPV 16 peptides are predictors of tumor recurrence and long-term survival in patients with squamous cell invasive cervical cancer. Four hundred seventy-one cases included in two population-based case-control studies underwent follow-up evaluation. The survival and cause of death were ascertained for 410 cases (87%), with a median follow-up time of 4.6 years after diagnosis. HPV DNA was assessed using an L1 polymerase chain reaction (PCR)-based system and Southern hybridization (SH) on scraped cytologic specimens or biopsies. HPV 16 antibodies to E2, L2, and E7 peptides were detected with enzyme-linked immunosorbent assay (ELISA). Clinical stage was the only independent prognostic factor for recurrence or survival. Although seropositivity to HPV 16 E7/3 peptide predicted a twofold excess risk of mortality (adjusted hazards ratio [HRa] = 2.0; 95% confidence interval [CI], 1.2 to 3.3), the association was restricted to stage I (HRa = 6.6; 95% CI, 1.2 to 37.6) and II (HRa = 5.9; 95% CI, 2.1 to 16.5) patients. The presence of HPV DNA (HRa = 0.9; 95% CI, 0.5 to 1.5), different estimates of the HPV viral load and the HPV type identified were not predictors of tumor recurrence or survival. The presence of antibodies to HPV 16 E7 proteins is of prognostic value in early-stage cervical cancer. Our results provide strong evidence that detection and typing of HPV DNA in cervical cells or tissues is not a prognostic factor for recurrence or survival.

Patients with active cancer experience ischemic stroke via cryptogenic mechanisms, with cancer-associated hypercoagulability being considered a major contributor to such strokes. Despite the remarkably shortened survival of these patients, the clinical predictors of survival are poorly understood. We determined the clinical factors including D-dimer levels serving as the predictors of overall survival in these patients. Retrospective study was conducted on cancer patients who visited our hospital for acute ischemic stroke with cryptogenic mechanisms from April 2012 through November 2014. Demographics, clinical characteristics, imaging and laboratory results including coagulation markers were collected, and overall survival was calculated from the patient medical records and a governmental national database. A high D-dimer level was defined as a D-dimer level exceeding the median value from the study population (>5.50μg/ml). A total of 93 patients were identified, with a median survival of 62days (interquartile range 32-223days). A high D-dimer level (p=0.004; hazard ratio [HR] 2.01, 95% confidence interval [CI] 1.26-3.21), systemic metastases (p=0.02; HR 2.08, 95% CI 1.11-3.90), and diabetes mellitus (p=0.03; HR 1.78, 95% CI 1.03-3.10) were identified as independent predictors of poor overall survival using multivariate Cox proportional hazard analysis. Most of the patients (87%) were primarily treated with low-molecular-weight heparin (dalteparin, n=49; enoxaparin, n=32). The type of low-molecular-weight heparin had no association with survival. A high D-dimer level, systemic metastases, and diabetes are independent predictors of poor survival in cancer patients with cryptogenic stroke.

Aim of this study was to investigate predictors of survival in unstable patients with high SYNTAX-1-score. In significant unprotected left main coronary artery (ULMCA) stenosis, treatment options include percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG). While CABG is recommended for stable patients with ULMCA stenosis and a SYNTAX-1-score > 32, PCI may be preferable in unstable or high operative risk patients. Retrospective single-center all-comers registry study. A total of 142 patients underwent ULMCA-PCI (~72.9 years, 23.2% females, 54.2% survival in 2-year follow-up), 84 of whom had a SYNTAX-1 > 32 (37.4 ± 12.8). Patients in the high-SYNTAX-1-group (score > 32) were more often in an acute condition compared to low-SYNTAX-2-group (score ≤ 32) including acute myocardial infarction (76.2% vs. 57.4%, p = .024), cardiogenic shock (48.2% vs. 14.8%, p = .001), or need for mechanical support (36.1% vs. 11.1%, p = .001). Survival was predicted by the acute condition including cardiogenic shock (OR 0.06 and 0.05) and myocardial infarction (OR 0.03 and 0.34) in both groups. Performance of the SYNTAX-1-score was limited in our patient collective in both groups (c-index 0.65 vs. 0.63) while SYNTAX-2-PCI-score performed better (c-index 0.67 vs. 0.67). EuroScore II had the best discriminative ability (c-index 0.87 vs. 0.78). The majority of patients undergoing ULMCA-PCI presented in acute conditions with high SYNTAX-1-score, and is therefore underrepresented in clinical trials. Prognosis was best predicted by the acute condition and the EuroScore II. These data suggest that therapy in unstable patients should be guided by clinical condition over the anatomical SYNTAX-1-score.

e18004 Background: Neutrophil-to-lymphocyte ratio (NLR) is an easily attainable biomarker that is correlated with systemic inflammation and identifies increased risk of treatment complications and decreased survival in patients with cancer. Our objective was to investigate the use of NLR as an independent prognostic predictor of survival in patients with head and neck squamous cell carcinoma (HNSCC) treated with cisplatin chemotherapy. Methods: We conducted a retrospective study of 2,084 patients in the Veterans Health Affairs system with stages III–IVB head and neck squamous cell carcinoma diagnosed between 2000–2014 and treated with cisplatin-based chemoradiotherapy for curative intent. We calculated NLR values from laboratory values collected in the 30 days prior to initiation of chemoradiotherapy and dichotomized NLR using the Youden J-statistic (NLR = 3.64). We then compared outcomes using Cox proportional hazards methods, adjusting for sociodemographic characteristics (age, race, and sex), date of cancer diagnosis, smoking status, alcohol use, primary site of tumor, tumor characteristics (overall stage, T stage, and N stage), comorbidity score, eGFR, baseline neuropathy and hearing loss, BMI, and oncologic surgical procedures. Results: The cohort had a median age of 61. 99% of cases were male, 82% were white, 13% were black, and 4% were Hispanic. 36% of cases had an NLR &gt; 3.64 prior to treatment initiation. Median overall survival was 32.6 months for the low-NLR group and 24.9 months for the high-NLR group. In unadjusted analyses, a high NLR was associated with an increased risk of all-cause death (hazard ratio [HR]: 1.21; 95% CI 1.08–1.34). In adjusted analyses, high NLR retained significance and predicted overall survival (HR: 1.15; 95% CI 1.02–1.30). We also performed a secondary analysis for death within six months of cancer diagnosis; high NLR was associated with &gt; 50% increased risk of death after adjustment (HR: 1.56; 95% CI 1.04–2.33). Conclusions: In this large cohort of Veterans with advanced HNSCC undergoing chemoradiotherapy, NLR was an independent prognostic predictor of survival. NLR may be a useful clinical risk stratification tool prior to chemoradiotherapy initiation.

The presence of histologic necrosis in the primary tumor of patients with renal cell carcinoma (RCC) has been suggested to be an important predictor of survival. The authors investigated the relation of tumor necrosis to other clinicopathologic factors known to be important prognostic indicators for patients with RCC. The records of 311 patients undergoing treatment for RCC were evaluated for basic clinicopathologic information including TNM classification, nuclear grade, Eastern Cooperative Oncology Group (ECOG) performance status (PS), disease recurrence, and survival. The presence and extent of histologic necrosis of the primary tumors was recorded and correlated with clinicopathologic factors, carbonic anhydrase IX and Ki-67 expression, disease recurrence, and survival. The presence of necrosis in the primary tumor of patients with RCC compared with patients with RCC without necrosis was associated with higher T classification (P < 0.0001), the presence of lymph node disease (P = 0.009), the presence of metastases (P < 0.0001), higher grade (P < 0.0001), greater mean tumor size (P < 0.0001), an ECOG PS score > or = 1 (P = 0.007), higher University of California-Los Angeles Integrated Staging System (UISS) category (P < 0.0001), and higher Ki-67 expression (P < 0.0001). The extent of necrosis in the primary tumor was associated with the presence of lymph node disease (P = 0.009) and the presence of metastases (P < 0.0001), and correlated with higher T classification (sigma = 0.31, P < 0.0001), poorer ECOG PS (sigma = 0.18, P = 0.002), higher grade (sigma = 0.33, P < 0.0001), greater tumor size (sigma = 0.40, P < 0.0001), higher UISS category (sigma = 0.37, P < 0.0001), and higher Ki-67 staining (sigma = 0.32, P < 0.0001). Patients with the presence of necrosis in the primary tumor demonstrated a lower 5-year disease-specific survival compared with patients without necrosis in the primary tumor (36% vs. 75%; P < 0.0001). Multivariate analysis demonstrated that T classification (P < 0.0001), distant metastases (P < 0.0001), and ECOG PS (P < 0.0001) were independent predictors of DSS, whereas the presence of necrosis was not (P = 0.1100). Substratification into localized and metastatic disease demonstrated that the presence of necrosis was an independent predictor of survival in patients with localized (P = 0.025), but not metastatic (P = 0.44), disease. The extent of necrosis was not an independent predictor of survival (P > 0.05). Patients with the presence of necrosis in the primary tumor had a lower 5-year disease recurrence-free rate compared with patients without the presence of necrosis (62% vs. 92%, P < 0.0001). The presence of necrosis in the primary tumor was associated with adverse prognostic factors such as high T classification, presence of lymph node disease and metastases, high grade, large tumor size, and poor ECOG PS. The extent of necrosis was found to be associated with the presence of lymph node disease and metastases and correlated with higher T classification, higher grade, greater tumor size, poorer ECOG PS, and higher UISS category. The presence of this histologic variant was an independent predictor of poor survival in patients with localized, but not metastatic, disease. In addition, Ki-67 expression served as a valuable surrogate marker for the presence of histologic tumor necrosis.

The current study was conducted to identify histologic predictors of survival in patients with localized, lymph node-negative (Stage I, N0M0) primary mucosal melanomas of the head and neck (HNMM). The histology of 39 sinonasal, 20 oral, 1 pharyngeal, and 1 laryngeal Stage I HNMM was reviewed by 2 pathologists without knowledge of patient outcome. The invasion was evaluated as Level I: melanoma in situ (without invasion or with microinvasion only); Level II: invasion into the lamina propria only; and Level III: invasion into deep tissue (e.g., skeletal muscle, bone, or cartilage). The tumor architecture was defined as pseudopapillary when tumor cells clustered around blood vessels resembling papillae and sarcomatoid when they resembled high-grade pleomorphic sarcoma. Survival analysis was performed with Kaplan-Meier survival curves using disease-specific survival (DSS) as the endpoint. The 5-year DSS rate was 43% (median, 41.5 months). The median survival was found to decrease significantly with increasing level of invasion: Level I (n = 4): 138 months; Level II (n = 29): 69 months; and Level III (n = 28): 17 months (P = 0.003). The presence of pseudopapillary and sarcomatoid architecture (n = 20) and undifferentiated cells (n = 16) were found to be associated with a significantly poor DSS (P < 0.05). However, on multivariate analysis, only the level of invasion remained an independent predictor of survival (P = 0.03). Tumor thickness, vascular invasion, and necrosis were found to have no significant influence on survival. Microstaging according to invasion into three tissue compartments was found to be a significant and independent predictor of poor survival in patients with localized, lymph node-negative, Stage I HNMM. The presence of sarcomatoid and pseudopapillary architecture and undifferentiated cells also appear to be associated with significantly poor DSS.