Stage Overall Survival Research Articles

Abstract B10: High-dimensional (30-plex) imaging mass cytometry on tissue microarray identifies novel PD-L1-inclusive immunophenotypes associated with overall survival in stage III melanoma

Abstract We sought to determine the subcellular distribution of 30+ immune-related markers including PD-L1 in stage III melanoma tumor tissues (nuclear, cytoplasmic, surface) using novel imaging mass cytometry technology that enables simultaneous detection of over 30 immune and tumor markers. Metal-tagged antibodies were used to stain stage III melanoma tissues similarly to an IHC-based protocol, followed by laser ablation and mass cytometry using the Helios® and Hyperion® technology (Fluidigm). Markers for immune subsets included CD45, CD3, CD4, CD8, PD-1, Granzyme B, FoxP3, CD11b, CD11c, CD107, CD20, Vista, and CD68. Markers for tumor cell phenotyping included PD-L1 (intracellular and extracellular domain specific), E-cadherin, B-catenin, PD-L2, and keratin 8/18. Structural, inflammatory, survival, and signaling markers included Ki67, p53, p-tyrosine, Bcl-2, Cl-caspase 3, histone H3, collagen-1, actin, and arginase-1. We further validated subcellular distribution of PD-L1 in the same patient tumor cores using fluorochrome-labeled antibodies and 100X confocal microscopy to show difference in surface-only, cytoplasmic-only, and nuclear PD-L1. We then assessed the association between subcellular PD-L1 and immune populations in the tumor microenvironment, along with overall and recurrence-free survival. We wrote custom algorithms for data processing to identify novel immune subsets, ran SPADE and viSNE analyses for cross-validation, and employed Imaris Bitplane software to validate our own algorithms for immune population identification. Overall, we found that intracellular-only PD-L1 in tumor tissues has the highest correlation (Pearson r) to CD11b, FoxP3, PD-1, arginase, Ki67, PD-L2 and nuclear stain iridium, while extracellular (surface) PD-L1 in tumors has the highest correlation (Pearson r) to FoxP3, PD-1, arginase, Ki67, PD-L2 and Vista. We identified two novel immunophenotypes (histone-3+/p-tyrosinehi /Vistalo / PD-L1-ICDlo / PD-L1-ECDlo and CD11bhi / PD-L1-ICDhi / PD-L1-ECDhi) that are positively associated with overall patient survival. Of note, only phospho-Tyrhi was significantly associated with RFS. This work highlights the use of cutting-edge technology that can employ the highest multiplexing available for assessing novel interactions of 30+ tumor tissue markers for identification of novel immunophenotypes and biomarker in stage III melanoma patients. Our novel study showcases a novel methodologic approach to high-throughput analysis of retrospective profiling of the melanoma tumor immune microenvironment on a single IHC slide, followed by appropriate and rigorous cross-validation using Fluidigm’s novel CyTOF imaging technology. Our study provides a groundwork for this powerful, novel technology in translational and clinical research for biomarker identification and identification of novel combinatorial markers that may predict overall and recurrence-free survival in stage III melanoma. Citation Format: Heather G. Hambright, Anand V.R. Kornepati, Dai Ogata, Roland R.L. Bassett, Suhendan Ekmekcioglu, Elizabeth A. Grimm, Tyler J. Curiel. High-dimensional (30-plex) imaging mass cytometry on tissue microarray identifies novel PD-L1-inclusive immunophenotypes associated with overall survival in stage III melanoma [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr B10.

Abstract B18: The expression of CD74-regulated inflammatory markers in stage IV melanoma: Risk of CNS metastasis and patient survival

Abstract Innate inflammatory features have been found in melanoma tumors from patients at all stages, and ongoing molecular analysis by us and others has identified specific inflammatory proteins expressed by tumors cells in those patients with the worst prognosis. We have previously observed impaired outcomes in patients with constitutive expression of inducible nitric oxide synthase (iNOS), Macrophage Migration Inhibitory Factor (MIF), and improved outcomes with CD74 expression in stage III melanoma (1-2). In this study, we tested our hypothesis that CD74-regulated inflammatory markers’ expression in stage IV melanoma tumors is associated with survival outcome and risk of developing CNS metastasis. We retrospectively identified 315 patients with stage IV melanoma. In a tissue microarray (TMA) of systemic metastasis specimens from these patients, we used immunohistochemical analysis to measure the expression of cells with CD74, MIF, iNOS, Nitrotyrosine (NT), cyclooxygenase (COX)-2, and microsomal prostaglandin E synthase-1 (mPGES1). We analyzed the association of those inflammatory markers with overall survival time (OS) and time to first CNS metastasis using Kaplan–Meier survival analyses. Tissue sections from 315 patients with distant metastatic melanoma were included in the TMA, of which 169 (54%) did not have CNS metastasis at the time of the last follow-up. The median age of the patients at the time of the stage IV diagnosis was 56 (range: 13–85 years). For OS, the expression of CD74 impacts overall survival in stage IV melanoma patients (p=0.0196). Moreover, the combination of tumor expression of CD74 and lack of MIF expression showed the advantage of OS in stage IV melanoma patients (p=0.0264). The expression of CD74 tended to be predictive of development or time to CNS metastasis. However, the expression of NT significantly impacted development or time to CNS metastasis (p=0.0008). To corroborate these findings, we further investigated the survival associations in the melanoma stage IV TCGA dataset for our markers of interest. Only high CD74 expression predicted better prognosis in stage IV melanoma patients when compared with low expression (p=0.0265). Our data validate CD74 as a useful prognostic tumor cell protein marker associated with favorable OS in stage IV melanoma. The tumor NT expression strongly predicts an increased risk of developing CNS metastasis in those patients. Our understanding of complex cancer cell and their response in the chronic inflammation environment would help us develop better treatments for melanoma.

Clinical and Demographic Profile of Cutaneous Melanoma: Pakistani Perspective

BACKGROUNDCutaneous melanomas (CMs) account for only a small proportion of skin cancers, however these are responsible for most skin cancer deaths. There has been a consistently increasing trend in their incidence across the globe.METHODSThis prospective case series study spanned over a period of three years. All patients with histologically confirmed CMs were included.RESULTSThere were 31 patients including 28 males and 3 females with the mean age of 58.25±11.33 years. The histological subtypes included 13 cases (41.93%) of nodular melanoma (NM), 11 patients (35.5%) of acral lentiginous melanoma (ALM), 3 cases (9.67%) of superficial spreading melanoma (SSM) and lentigo maligna melanoma (LMM) and one case (3.22%) of desmoplastic melanoma. Two patients (6.45%) presented with stage II, whereas 21 patients had (67.74%) stage III melanoma. There were 8 patients (25.80%) with stage IV. Time interval between onset of the lesion and first presentation to hospital ranged from 6 to 17 weeks with a mean of 12.45±3.2 weeks. The overall median survival for patients with stage III and IV was 8.75 months. The overall survival for stage II at one year was 100%.CONCLUSIONCMs more frequently affected males aged ≥58 years. Feet, face, trunk, hands and scalp were the affected anatomical body parts in decreasing order of frequency. NM and ALM were the more common histological subtypes. Majority of patients presented late and advanced stages of melanoma. Awareness about the sinister course of the disease will ensure early presentation with better treatment outcome.

Abstract 2437: Clinical, biological and translational significance in gastric cancer of reprimo-like gene, an uncharacterized member of the reprimo gene family

Abstract Background: Gastric cancer (GC) is one of the leading causes of cancer death. Elucidating the molecular bases of GC might contribute to develop opportune diagnostic strategies. Reprimo-like (RPRML) is a poorly characterized member of the Reprimo gene family. The founding member of this family, Reprimo, is reported to be a putative tumor suppresser gene and candidate biomarker for GC diagnosis. We have recently reported the downregulation of RPRML expression in GC tissues compared to paired normal adjacent tissues, and that in vitro expression is regulated by DNA methylation. We hypothesize that RPRML promoter methylation may act as a non-invasive biomarker for GC. Methods: RPRML expression was evaluated by immunohistochemistry (IHC) in 91 GC cases from The Gastric Cancer Task Force (NCT03158571). Two pathologists scored staining by multiplying the proportion and the intensity of stained cells (range 0-3). Cox proportional hazard ratio was applied to determine an association between RPRML IHC score and global survival, after adjusting by stage. In addition, we investigated the effect of RPRML overexpression in GC cell behavior in vitro through the stable transfection and sorting of RPRML coupled to GFP or GFP alone in the AGS cell line. Functional assays included Ki67 immunofluorescence, colony formation, soft agar, transwell migration and wound healing assays. All experiments were performed in biological triplicate and Kruskal-Wallis statistical analysis applied. The Methylight assay was used to quantify methylated RPRML DNA copies in plasma samples from 25 GC cases (tumor bank repository BTHCUCH) and 25 healthy donors under an endoscopic surveillance program (PREVECAN). ROC curve analysis was performed to determine the cut-off value for the highest sensitivity and specificity. Results: Among 91 GC cases, RPRML expression showed a median IHC score of 0.024 (range 0-2.45). By using the median as a cut-off point, low RPRML IHC score was associated with poor overall survival of stage III and IV GC patients (HR=2.13, 95%CI:1.1-4.1, p=0.02). In vitro overexpression of RPRML inhibited cell proliferation (p=0.04) and resulted in reduced clonogenic capacity (p=0.001) and anchorage independent growth (p≤0.0001). Furthermore, RPRML overexpression retarded migration and wound healing in AGS cells. Methylation of RPRML DNA in plasma samples discriminated between GC patients and controls with an AUC of 0.66. Utilizing a cut-off value of 0.15 copies/ul, sensitivity was 56% (95%CI: 34.9 - 75.6) and specificity 72% (95%CI: 50.6 - 87.9). Conclusion: RPRML downregulation associated with poor survival of advanced stage GC patients. In accordance, ectopic overexpression of RPRML in vitro inhibited biological characteristics associated with tumor progression, suggesting that RPRML may have a tumor suppressor role in GC. Future analysis will determine if the methylation of RPRML is a candidate marker for the non-invasive detection of GC. Grants: CONICYT-FONDAP 15130011 and Fondecyt 1191928 Citation Format: Maria Alejandra Alarcon, Wilda Olivares, Andres Rodriguez, Maria Jose Maturana, Rocío Bustos, Iva Polakovicova, Miguel Cordova-Delgado, Matías Muñoz-Medel, Marcelo Garrido, Gareth I. Owen, Tomas De Mayo, Gonzalo Carrasco-Avino, Julio Amigo, Arnoldo Riquelme, Robinson Gonzalez, Carlos Barrientos, Edmundo Aravena, Franz Villarroel-Espíndola, Alejandro H. Corvalan. Clinical, biological and translational significance in gastric cancer of reprimo-like gene, an uncharacterized member of the reprimo gene family [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2437.

How does chronic obstructive pulmonary disease affect the survival of patients with stage 4 lung cancer?

Lung cancer risk is increased in COPD. However, it is not clear how COPD affects the course of lung cancer. To determine whether the overall survival of stage 4 lung cancer patients differ in various COPD stages. A cross-sectional retrospective study. We screened lung cancer patients with ICD code: C34 and included stage 4 lung cancer patients with histological diagnosis and pulmonary function tests at admission in the study. Demographic data, stages, metastasis sites and number of metastases, performance status, pulmonary function tests, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages, arterial blood gasses and treatment methods were recorded on a standardised database. We checked their dates of death from national database. Data were evaluated with SPSS programme version 18. Out of 900 patients, 146 patients had stage 4 disease at the time of diagnosis and, 127 patients had COPD. There was a significant difference between survivals of stage 4 cancer patients with different COPD stages. As COPD stage increased, overall survival worsened (P=0.037). Factors affecting survival were bone metastasis (P=0.01, OR=1.72), liver metastasis (P=0.04, OR=1.87), brain metastasis (P=0.001, OR=2.6), having N 2-3 disease (P=0.01, OR=1.79) and GOLD 4 COPD (P=0.01, OR=2.28). As COPD becomes more severe, overall survival rates of stage 4 patients worsen. Bone metastasis, liver metastasis, brain metastasis, having N2-3 disease and GOLD 4 COPD worsen the overall survival.

The Impact of Histologic Subtype on Receipt of Adjuvant Chemotherapy and Overall Survival in Stage III Colon Cancer: a Retrospective Cohort Analysis.

The impact of adjuvant chemotherapy (AT) on resected colon adenocarcinoma based on histologic subtype is poorly defined and extrapolated from patients with advanced disease. We evaluated the receipt and effect of AT on overall survival stratified by histologic subtype-mucinous, non-mucinous, and signet ring adenocarcinomas. A retrospective cohort study from 2004 to 2015 was conducted using the National Cancer Database. Patients with colon adenocarcinoma who underwent curative resection with pathologic stage III were included. Appendiceal and rectal tumors were excluded. The predictor variable was histologic subtype, and outcome variables were overall survival and receipt of AT. Absolute survival was increased for mucinous, non-mucinous, and signet ring tumors with receipt of AT (88.1, 108.9, and 38.1months, respectively). In multivariable analysis, there was no difference in overall survival for mucinous patients relative to non-mucinous patients. In subgroup analysis, a modest survival advantage for non-mucinous patients relative to the mucinous patients was observed (HR, 0.92; 95% CI, 0.89-0.95). In multivariable modeling, non-mucinous and signet ring adenocarcinoma had decreased odds of receipt of AT relative to mucinous adenocarcinoma patients. Histologic subtype is an important prognostic factor for overall survival for stage III colon adenocarcinoma. Although the magnitude of the benefit of AT may vary in stage III curatively resected patients, it has a substantial survival benefit across all histologic subtypes. Based on these observations, there is no indication that patients with stage III mucinous adenocarcinoma of the colon should not receive AT. All patients with resected stage III colon cancer should be referred for AT regardless of histologic subtype.

Prognostic role of aberrant mTOR activation in patients with stage II and III colorectal cancer.

Aim: This study aimed to develop an effective risk predictor for patients with stage II and III colorectal cancer (CRC). Materials & methods: The prognostic value of p-mTOR (Ser2448) levels was analyzed using Kaplan-Meier survival analysis and Cox regression analysis. Results: The levels of p-mTOR were increased in CRC specimens and significantly correlated with poor prognosis in patients with stage II and III CRC. Notably, the p-mTOR level was an independent poor prognostic factor for disease-free survival and overall survival in stage II CRC. Conclusion: Aberrant mTOR activation was significantly associated with the risk of recurrence or death in patients with stage II and III CRC, thus this activated proteins that may serve as a potential biomarker for high-risk CRC.

HIPEC in advanced epithelial ovarian cancer: why is there controversy?

The randomized OVHIPEC study provided further evidence that adding heated intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery significantly improved recurrence-free and overall survival in stage III epithelial ovarian cancer (EOC) patients, who were ineligible for primary cytoreductive surgery due to extensive intraperitoneal disease. Because opinions have been divided as to whether HIPEC is now a new standard of care for advanced EOC, the pros and cons of this approach are examined. A comparison with the ongoing discussion about the role of intraperitoneal chemotherapy is made. For both techniques, experience is crucial and a learning curve essential. Compared with intraperitoneal chemotherapy, intraoperative application of HIPEC provides superior distribution through the peritoneal cavity. HIPEC, as given in OVHIPEC, did not significantly increase adverse events, had no negative effect on quality of life and was cost-effective. Despite the ongoing debate about HIPEC, an important first step in attempting to demonstrate the efficacy of HIPEC in the first-line setting has been made with OVHIPEC. Critics have been of value to optimize future trials with HIPEC in patients with EOC.

Long-term Oncologic Outcomes of Single-Incision Plus One-Port Laparoscopic Surgery for Rectal Cancer

Single-incision plus one-port laparoscopic surgery (SILS+1) for rectal cancer reduces technical difficulties of pure single-incision laparoscopic surgery (SILS) keeping good cosmetic results. However, the adequate long-term oncological outcomes of SILS+1 for rectal cancer were not documented in the literature. Data from 136 patients (86 males) who performed an elective surgery with SILS+1 for stage I to III rectal cancer were reviewed, and its 5-year oncologic outcomes were evaluated. The median follow-up period was 57 months. A total of 18 patients (13.3%) experienced recurrence, including two peritoneum and three local recurrences. In these five patients, four patients except one patient with relapse at an anastomotic site were pT4 patients. The 5-year overall survival for stage I, II, and III patients were 98.1, 91.2, and 88.5%, respectively, and the 5-year cancer-specific survival for stage I, II, and III patients was 100, 97.1, and 97.8%, respectively. The long-term oncological safety of SILS+1 for rectal cancer was demonstrated with an excellent 5-year cancer-specific survival.

A Tertiary Cancer Center Experience of 52 Cases of Primary Ovarian Mucinous Adenocarcinomas.

Background Primary mucinous epithelial ovarian adenocarcinoma (mEOC) constitutes a small percentage (2–5%) of ovarian cancer. Our aim is to understand the clinicopathological characteristics and survival results of patients with mEOC after a long-term follow-up. Materials and Methods This is a retrospective study of primary mEOC cases treated at a tertiary cancer center in India, from January 1, 2005, to December 31, 2012. Results Out of 958 malignant ovarian tumors, 52 (5.43%) were mucinous adenocarcinoma. Nearly 71.2% of cases were of early-stage disease, and the remaining were of advanced-stage disease. After a follow-up period of 63 months (range: 1–138 months), the 5-year actuarial overall survival for stages I, II, III, and IV was 92.5, 70, 38.5, and 0%, respectively. Among advanced-stage tumors, half of them progressed without undergoing cytoreductive surgery and died. Conclusion Most of the mEOC cases present in early stages and have good clinical outcome. Patients with advanced-stage disease do not respond well to standard chemotherapy regimens in use and have poor survival figures. The use of primary cytoreduction should be considered in the place of interval cytoreduction for advanced mEOC.

Abstract P2-17-02: Locoregional therapy targeted at the primary tumour improves overall survival in patients presenting with de novo stage IV metastatic breast cancer: A systematic review and meta-analysis of real-world data with 201598 patients

Abstract Background: De novo stage IV metastatic breast cancer is a complex disease that is traditionally treated using systemic therapy. There is mounting evidence that locoregional therapy (LRT), defined as resection of the primary tumour and/or localised radiotherapy, could be associated with survival improvements. We aimed to conduct a meta-analysis to inform decision making. Methods: Using the PubMed, Cochrane and Ovid SP databases, a literature review and meta-analysis was undertaken to assess whether LRT of the primary tumour in metastatic breast cancer prolongs survival. Results: 48 studies met the criteria for analysing the efficacy of all locoregional treatments (radiotherapy and/or surgery) and 44 studies were suitable for the analysis of surgery-only treatment of the primary. Studies were analysed for the impact of LRT on survival. All LRT resulted in a significant 32.9% reduction in mortality with LRT (N=48; HR=0.671: 95% CI 0.624-0.721). Primary resection alone resulted in a significant 36.9% mortality (N=44; HR=0.631: 95% CI 0.591-0.674). Conclusions: This is the largest meta-analysis regarding this question to date. LRT seems to improve overall survival in stage IV disease at initial diagnosis and should be considered in selected patients after a multidisciplinary discussion. Citation Format: Salim Tayeh, Ritika Gera, Hiba El Hage Chehade, Umar Wazir, Abdul Kasem, Kefah Mokbel. Locoregional therapy targeted at the primary tumour improves overall survival in patients presenting with de novo stage IV metastatic breast cancer: A systematic review and meta-analysis of real-world data with 201598 patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-17-02.

Nomogram for predicting overall survival in stage II-III colorectal cancer.

PurposeThe overall survival (OS) of patients diagnosed with stage II‐III colorectal cancer (CRC) can vary greatly, even between patients with the same tumor stage. We aimed to design a nomogram to predict OS in resected, stage II‐III CRC and stratify patients with CRC into different risk groups.Patients and MethodsBased on data from 873 patients with CRC, we used univariate Cox regression analysis to select the significant prognostic features, which were subjected to the least absolute shrinkage and selection operator (LASSO) regression algorithm for feature selection. Cross‐validation was used to confirm suitable tuning parameters (λ) for LASSO logistic regression. Then, the nomogram was used to estimate 3‐ and 5‐year OS based on the multivariable Cox regression model. The survival curves of the two groups were produced using the Kaplan‐Meier method. Risk group stratification was performed to assess the predictive capacity of the nomogram.ResultsPreoperative mean platelet volume, preoperative platelet distribution width, monocytes, and postoperative adjuvant chemotherapy were identified as independent prognostic factors by LASSO regression and integrated for the construction of the nomogram. The nomogram provided good discrimination, with C‐indices of 0.67 and 0.69 for the training and validation sets, respectively. Calibration plots illustrated excellent agreement between the nomogram predictions and actual observations for 3‐ and 5‐year OS. Moreover, a significant difference in OS was shown between patients stratified into different risk groups (P < .001).ConclusionWe constructed and validated an original predictive nomogram for OS in patients with CRC after surgery, facilitating physicians to appraise the individual survival of postoperative patients accurately and identify high‐risk patients who need more aggressive treatment and follow‐up strategies.

Impact of intraoperative staging of gastric cancer on long-term survival.

302 Background: The preoperative stage and intraoperative stage of gastric cancer were unified as the clinical stage in the 8th edition of the TNM classification (UICC). Although there are some reports about the relationship between preoperative stage and prognosis, the relationship between intraoperative stage and prognosis remains unclear. The aim of this study was to clarify the impact of intraoperative diagnosis and staging on long-term survival. Methods: Overall survivals were examined in 915 patients who underwent curative resection for gastric adenocarcinoma between April 2011 and March 2019 in our hospital. Results: The median age of the patients was 69 years (27-90 years), including 585 male and 330 female. The median follow-up period was 33.6 months (0.1-86.7 months). The number of the patients according to intraoperative stage were 641(70.1 %) in stageI, 15(1.6%) in stageIIA, 135(14.8%) in stageIIB, 111(12.1%) in stageIII, 12(1.3%) in stageIVA and 1(0.1%) in stageIVB. The hazard ratios of intraoperative stage for overall survival were as follows (ref: StageI); StageIIA, 6.990 (95% CI: 2.473-19.760, p &lt; 0.001), StageIIB, 2.234 (95% CI: 1.220-4.092, p = 0.009), StageIII, 4.091 (95% CI: 2.416-6.928, p &lt; 0.001), StageIVA, 6.061 (95% CI: 2.150-17.080, p &lt; 0.001), StageIVB, 14.92 (95% CI: 2.035-109.3, p = 0.008). Conclusions: The survival of intraoperative StageIIA was poorer than StageIIB/III. Intraoperative positive lymph node metastasis could be negative impact of survival, even if tumor invasion was T1 or T2.

Long-term survival of robotic lobectomy for non-small cell lung cancer: a literature review

Even though robotic-assisted surgery is increasingly used for resection of non-small cell lung cancer (NSCLC), data on long-term oncologic outcomes of robotic surgery are still not well defined. The primary endpoint of this review is to analyse the long-term results of robotic lobectomy in NSCLC patients. A systematic research was performed using the PubMed database. Articles published from January 2008 to January 2019 were included. We excluded studies that did not provide results for the long-term outcomes of robotic lobectomy, studies that had fewer than 50 cases and ones that focused on results of sub-lobar resections. Therefore, ten eligible studies were included in this analysis. In total, 2873 patients, with a mean age ranging between 66 and 68 years, who underwent robotic lobectomy for NSCLC, were analysed. Most patients (81%) had early-stage disease. The five-year overall survival for stage I disease fluctuated between 77% and 100%. The five-year disease-free survival was reported to be near 73%. We can conclude that robotic assisted lobectomy is an effective minimally-invasive procedure for lung resection. The current literature shows that robotic lobectomy is associated with long-term survival and lasting disease-free survival, equivalent to those reached by video-assisted thoracic surgery and open approach.

Cancer patients in complementary and alternative medicine: More harm

Not available.

THE PROSPECTS FOR THE USE OF microRNA AS DIAGNOSTIC AND PROGNOSTIC MELANOMA BIOMARKERS

Despite recent advances in targeted and immune therapy, 5‑year overall survival in stages III–IV of melanoma is 50 and 10–20 %, respectively. Modern melanoma biomarkers, which are used in clinical practice, are not sufficiently effective for early diagnosis and prognosis assessment. In the last decade, circulating microRNAs (miRNAs) have come to be regarded as “ideal” melanoma biomarkers. This article presents the characteristics of miRNA biogenesis, as well as provides a critical review of circulating miRNAs as promising diagnostic and prognostic melanoma biomarkers.

Prognostic nomograms for predicting cause-specific survival and overall survival of stage I\u2013III colon cancer patients: a large population-based study

BackgroundThe purpose of this study was to build functional nomograms based on significant clinicopathological features to predict cause-specific survival (CSS) and overall survival (OS) in patients with stage I–III colon cancer.MethodsData on patients diagnosed with stage I–III colon cancer between 2010 and 2015 were downloaded from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox analyses were used to identify independent prognostic factors, which were used to construct nomograms to predict the probabilities of CSS and OS. The performance of the nomogram was assessed by C-indexes, receiver operating characteristic (ROC) curves and calibration curves. Decision curve analysis (DCA) was used to compare clinical usage between the nomogram and the tumor–node–metastasis (TNM) staging system.ResultsBased on the univariate and multivariate analyses, features that correlated with survival outcomes were used to establish nomograms for CSS and OS prediction. The nomograms showed favorable sensitivity at predicting 1-, 3-, and 5-year CSS and OS, with a C-index of 0.78 (95% confidence interval (CI) 0.77–0.80) for CSS and 0.74 (95% CI 0.73–0.75) for OS. Calibration curves and ROC curves revealed excellent predictive accuracy. The clinically and statistically significant prognostic performance of the nomogram generated with the entire group of patients and risk scores was validated by a stratified analysis. DCA showed that the nomograms were more clinically useful than TNM stage.ConclusionNovel nomograms based on significant clinicopathological characteristics were developed and can be used as a tool for clinicians to predict CSS and OS in stage I–III colon cancer patients. These models could help facilitate a personalized postoperative evaluation.

Results of the Phase 3 VITAL Study of NEOD001 (Birtamimab) Plus Standard of Care in Patients with Light Chain (AL) Amyloidosis Suggest Survival Benefit for Mayo Stage IV Patients

Results of the Phase 3 VITAL Study of NEOD001 (Birtamimab) Plus Standard of Care in Patients with Light Chain (AL) Amyloidosis Suggest Survival Benefit for Mayo Stage IV Patients

Lymphopenia predicts poor prognosis in older gastric cancer patients after curative gastrectomy.

Total lymphocyte count in preoperative peripheral blood is associated with prognosis in various cancers. The predictive value of preoperative total lymphocyte count for survival was assessed in older gastric cancer patients after gastrectomy. A total of 200 gastric cancer patients aged ≥75 years who underwent curative resection from 2000 to 2014 were included in this retrospective study. The cut-off value of total lymphocyte count in preoperative peripheral blood was determined using receiver operating characteristic curve analysis, and the association with prognosis was examined. The cut-off value of total lymphocyte count was 1462/μL, and 94 patients were classified as low total lymphocyte count patients and 106 patients were classified as high total lymphocyte count patients. In univariate analysis, American Society of Anesthesiologists score ≥3, Charlson Comorbidity Index ≥3, total lymphocyte count <1462/μL, stage III, open approach, total gastrectomy, splenectomy and infectious complication were significantly associated with overall survival. In multivariate analysis, total lymphocyte count <1462/μL (P = 0.003), American Society of Anesthesiologists score ≥3 (P = 0.01) and stage III (P = 0.017) were independent prognostic factors. Low total lymphocyte count significantly reduced overall survival in stage I (P = 0.037) and II (P = 0.009) patients, but not stage III patients (P = 0.29). Total lymphocyte count in preoperative peripheral blood can predict postoperative survival of older patients with relatively early-stage gastric cancer. Geriatr Gerontol Int 2019; 19: 1215-1219.

Treatment patterns and outcomes in goblet cell carcinoid tumors of the appendix.

Goblet cell carcinoid (GCC) tumors of the appendix are a rare malignancy. We aim to examine the overall survival per stage and the relationship between different treatment modalities and outcomes for patients with GCC tumors of the appendix. We identified patients with GCC tumors of the appendix from the National Cancer Database. The main outcome was overall patient survival and cox proportional hazard models were used to ascertain predictors of survival. There were 2552 patients identified. The median age of diagnosis was 57 (interquartile range: 49-65) and 52.3% of patients were female. The 5-year survival for Stage I disease was 91.1% (95% confidence interval [CI]: 82.2%-95.7%), for Stage II disease was 90.5% (95% CI: 85.8%-93.7%), for Stage III disease was 57.0% (95% CI: 45.0%-67.3%), and for Stage IV disease was 18.9% (95% CI: 9.3%-31.0%). In a Cox proportional hazard model, older age (hazard ratio [HR]: 1.1; 95% CI: 1.03-1.12; P < .001), lymph node metastasis (HR: 6.9; 95% CI: 2.76-17.01; P < .001), and positive surgical margins (HR: 2.9; 95% CI:1.13-7.26; P = .003) were associated with worse overall survival for Stages I to III disease while only older age (HR: 1.03; 95% CI: 1.002-1.06; P = .04) was associated with worse overall survival for Stage IV disease. Patients with GCC tumors of the appendix who have the nonmetastatic disease have a high 5-year survival. We have identified several prognostic factors for GCC.