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This research presents a novel patch antenna prototype that operates in the THz range for early detection of malignant cancerous cells. The antenna has dimensions of 100 µm × 100 µm and achieves −27.3 dB return loss at an operating frequency of 2.34 THz. The proposed sensor is optimized for a polyimide substrate with a dielectric constant of 3.5 and thickness of 15.7 µm. The prototype's sensitivity and performance are evaluated by simulating different malignant neoplasms using High-Frequency Simulation Software (HFSS) for five types of breast cancer cells. The results indicate that the variation in resonant frequency and the S21 parameter between malignant cells and healthy breast cells are the primary factors that determine the sensitivity of the prototype. The proposed patch antenna's high sensitivity and low profile make it a promising solution for the early detection and prognosis of cancerous cells. [ABSTRACT FROM AUTHOR]

Adrenocortical carcinoma is a malignant tumor with a poor prognosis and a frequent metastatic extension. In very rare cases, a cardiac metastatic disease may occur, and surgical resection is essential for its management. MR-guided stereotactic radiotherapy is an attractive radiotherapy modality for the treatment of mobile thoracic tumors, enabling the target to be monitored continuously during irradiation, while the dosimetric plan can be adapted daily if necessary. We report here the case of a patient with intracardiac metastasis secondary to malignant adrenocortical carcinoma, treated with magnetic resonance imaging-guided stereotactic radiotherapy. [ABSTRACT FROM AUTHOR]

PANoptosis is a newly recognized inflammatory pathway for programmed cell death (PCD). It participates in regulating the internal environment, homeostasis, and disease process in various complex ways and plays a crucial role in tumor development, but its mechanism of action is still unclear. In this study, we comprehensively analyzed the expression of 14 PANoptosis-related genes (PANRGs) in 28 types of tumors. Most PANRGs are upregulated in tumors, including Z-DNA binding protein 1 (ZBP1), nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing 3 (NLRP3), caspase (CASP) 1, CASP6, CASP8, PYCARD, FADD, MAP3K7, RNF31, and RBCK1. PANRGs are highly expressed in GBM, LGG, and PAAD, while their levels in ACC are much lower than those in normal tissues. We found that both the CNV and SNV gene sets in BLCA are closely related to survival performance. Subsequently, we conducted clustering and LASSO analysis on each tumor and found that the inhibitory and the stimulating immune checkpoints positively correlate with ZBP1, NLRP3, CASP1, CASP8, and TNFAIP3. The immune infiltration results indicated that KIRC is associated with most infiltrating immune cells. According to the six tumor dryness indicators, PANRGs in LGG show the strongest tumor dryness but have a negative correlation with RNAss. In KIRC, LIHC, and TGCT, most PANRGs play an important role in tumor heterogeneity. Additionally, we analyzed the linear relationship between PANRGs and miRNA and found that MAP3K7 correlates to many miRNAs in most cancers. Finally, we predicted the possible drugs for targeted therapy of the cancers. These data greatly enhance our understanding of the components of cancer and may lead to the discovery of new biomarkers for predicting immunotherapy response and improving the prognosis of cancer patients. [ABSTRACT FROM AUTHOR]

Background: The mechanisms of distant metastasis in pancreatic cancer (PC) have not been elucidated, and this study aimed to explore the risk factors affecting the metastasis and prognosis of metastatic patients and to develop a predictive model. Method: Clinical data from patients meeting criteria from 1990 to 2019 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database, and two machine learning methods, random forest and support vector machine, combined with logistic regression, were used to explore risk factors influencing distant metastasis and to create nomograms. The performance of the model was validated using calibration curves and ROC curves based on the Shaanxi Provincial People's Hospital cohort. LASSO regression and Cox regression models were used to explore the independent risk factors affecting the prognosis of patients with distant PC metastases. Results: We found that independent risk factors affecting PC distant metastasis were: age, radiotherapy, chemotherapy, T and N; the independent risk factors for patient prognosis were: age, grade, bone metastasis, brain metastasis, lung metastasis, radiotherapy and chemotherapy. Conclusion: Together, our study provides a method for risk factors and prognostic assessment for patients with distant PC metastases. The nomogram we developed can be used as a convenient individualized tool to facilitate aid in clinical decision making. [ABSTRACT FROM AUTHOR]

Background: Adenoid cystic carcinoma (ACC) in Bartholin's gland is an uncommon malignant tumor. These tumors have a vague clinical feature, so they are diagnosed late and discovered at a high-level stage. Our case presented Three Recurrences and Three times Misdiagnosis of Adenoid Cystic Carcinoma (ACC). Case presentation: We report a case of adenoid cystic carcinoma arising in Bartholin's gland of a 64-year-old female patient that appeared after three previous vulvar tumors were excised. The patient underwent bilateral radiotherapy which was performed on the perineum. Conclusion: ACC of the vulvar sweat glands is prone to misdiagnosis and delay in both diagnosis and treatment. As seen in our case, it was misdiagnosed three times as Chondroid Syringoma. Further studies need to be conducted to better understand the tumor prognosis, and its optimal treatment options. [ABSTRACT FROM AUTHOR]

Background: The positive prediction of prognosis and immunotherapy within tertiary lymphoid structure (TLS) in cancerous tissue has been well demonstrated, including liver cancer. However, the relationship between TLS and prognosis in the peritumoral region of hepatocellular carcinoma (HCC) has received less attention. Few studies on whether TLS, as a typical representative of acquired immune cell groups, is associated with innate immune cells. The aim of this paper was to identify the prognostic role of peritumor TLS in HCC and to simply explore the relationship with neutrophils infiltration. Methods: This study included cancerous and paracancerous tissue from 170 patients after surgical resection of HCC. TLS was examined and identified by pathological H&E examination, and the impact on prognosis was further classified by determination of total TLS area. Immunohistochemical staining of CD15+ neutrophils was also performed on half of the cases. The obtained results were validated by external public database, as TLS has been widely shown to be tagged with 12 chemokines. Results: In peritumoral tissue, the TLS− group had better overall survival (OS) and disease‐free survival (DFS) outcomes compared with the TLS+ group. On the contrary, the intratumor TLS+ group showed better DFS outcomes. When further investigating the relationship between TLS area distribution and DFS, progressively worse prognosis was only found in the peritumor region with increasing TLS density (TLS− vs. TLSL vs. TLSH). In addition, neutrophil infiltration increased in parallel with TLS density in the peritumoral region, which was not observed in the intratumoral region. Conclusions: TLS might have a dual prognostic role in different regions of HCC. The abundance of peritumoral TLS is an independent influence of DFS. The inconsistent correlation between neutrophils and corresponding TLS in different regions may indicate different pathways of immune aggregation and may serve as an explanation for the different prognosis of TLS, which needs to be specifically explored. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to elucidate the role of quantitative tumor burden based on PET/CT of somatostatin receptors in well-differentiated neuroendocrine tumors (NETs). Methods: This study enrolled patients with [68 Ga]Ga-DOTA-NOC PET/CT-positive advanced NETs who did not receive medical treatment prior to PET/CT. Tumor burden was calculated using methods based on the background threshold and relative fixed threshold values (30%, 40%, and 50%). The prognostic value of the measured tumor burden in reference to overall survival (OS) and progression-free survival (PFS) on treatment with octreotide long-acting repeatable (LAR) was assessed using Cox regression analysis, Harrell's C-index, and survival analysis. A classification and regression tree (CART) was used to determine the optimal threshold for tumor burden. Results: A total of 204 patients were included. Somatostatin receptor-expressing tumor volume (SRETV) and liver SRETV derived from a relative fixed threshold of 30% (SRETV30 and liver SRETV30) were statistically significantly associated with OS (C-index: 0.802 [95% confidence interval (CI), 0.658–0.946] and 0.806 [95% CI, 0.664–0.948], respectively). Extrahepatic tumor burden was not correlated with OS (hazard ratio: 0.617, 95% CI: 0.241–1.574, P = 0.312). Among 155 patients with non-functional NETs with a ki-67 index of ≤ 10%, those with a high SRETV30 (P = 0.016) or high liver SRETV30 (P = 0.014) showed statistically significantly worse PFS on treatment with octreotide LAR. Patients receiving a higher dose of octreotide LAR normalized by SRETV30 or liver SRETV30 (a normalized dose or a liver normalized dose) showed prolonged PFS on treatment with octreotide LAR and a prolonged OS. Conclusion: Quantitative tumor burden based on [68 Ga]Ga-DOTA-NOC PET/CT was correlated with OS and PFS in patients with non-functional NETs with a ki-67 index of ≤ 10% who received octreotide LAR. Calculating normalized and liver normalized doses may help in selecting the starting dose of octreotide LAR. [ABSTRACT FROM AUTHOR]

ATP binding cassette subfamily C member 8 (ABCC8) encodes a protein regulating the ATP-sensitive potassium channel. Whether the level of ABCC8 mRNA in lower grade glioma (LGG) correlates with immune cell infiltration and patient outcomes has not been evaluated until now. Comparisons of ABCC8 expression between different tumors and normal tissues were evaluated by exploring publicly available datasets. The association between ABCC8 and tumor immune cell infiltration, diverse gene mutation characteristics, tumor mutation burden (TMB), and survival in LGG was also investigated in several independent datasets. Pathway enrichment analysis was conducted to search for ABCC8-associated signaling pathways. Through an online database, we found that ABCC8 expression in LGG was lower than in normal tissues. Then, the association of ABCC8 expression and immune cell infiltration in LGG was discussed. As we expected, the ABCC8 mRNA levels were negatively associated with non-T immune cell infiltration levels in all datasets. Consistently, TCGA_LGG RNA-seq data revealed that ABCC8 downregulated several non-T immune cell-associated signaling pathways in gene set enrichment analysis. Different ABCC8 expression groups showed diverse gene mutation characteristics and TMB. The high expression of ABCC8 was linked to improved survival of LGG patients. A pathway enrichment analysis of ABCC8-associated genes indicated that the GABAergic synapse signaling pathway might be involved in regulating immunity in LGG. Our findings show that ABCC8 reflects LGG tumor immunity and is an ideal prognostic biomarker for LGG. [ABSTRACT FROM AUTHOR]

The correlation between secreted phosphoprotein 1 (SPPf) and immune infiltration and the clinical correlation of SPP1 in head and neck squamous cell carcinoma(HNSC) were analyzed, and the potential value of SPP1 in the prognosis and individualized treatment of HNSC was clarified. The HNSC data from The Cancer Genome Atlas(TCGA) was used to analyze SPP1 expression. The clinical survival data from TCGA was used to evaluate the clinical prognostic value of SPP1. The clusterProfiler package of R language was applied for the enrichment analysis related to SPP1. The CIBERSORT function of R language was used to evaluate the infiltration of 22 kinds of tumor infiltrating immune cells in HNSC. Subsequently, the correlation analysis between tumor infiltrating immune cells and SPP1 expression was performed. Differential expression analysis found that SPP1 was highly expressed in HNSC (PcO.OOl). Clinical correlation analysis found that SPP1 expression was correlated with T stage (P = 0.001) and clinical stage (P = 0.013). The overall survival of patients with high SPP1 expression was significantly shorter than the patients with low SPP\expression (P = 0.020 4). Gene enrichment analysis found that SPP1 was associated with immunological functions and immune-related pathways in HNSC. Analysis of tumor infiltrating immune cells found that in the high SPP1 expression group, the infiltration proportions of M2 macrophages (P = 0.001 1), resting dendritic cells (P = 0.005 5), and activated mast cells (P = 0.048 8) increased, while the infiltration proportions of actived memory CD4+ T lymphocytes (P<0.001), plasma cells (P = 0.026 6), and resting mast cells (P = 0.038 6) decreased. The research results indicate that SPP1 acts as an oncogene in HNSC and is related to the clinical outcome of patients. SPPl may play an important role in the tumor immune microenvironment and may become a valuable prognostic biomarker and immunotherapy target in HNSC. [ABSTRACT FROM AUTHOR]

Objective To explore the effect of the expression changes of O-fucosyltransferase 1（POFUT1）in the tumor tissues on the prognosis of tumor patients and its mechanism. Methods Combined with the pan-cancer data sets obtained from the TCGA database and the GTEx database, we used the GEPIA2 and TIMER2 to compare the expression levels of POFUT1 in various types of tumors and paired normal tissues, and selected the tumor types with statistical differences. The prognosis of the above tumor patients with different POFUT1 levels was compared. The TIMER database and the estimate software package were used to screen the tumors with the strongest correlation between POFUT1 and the level of immune cell infiltration, and then we analyzed the correlations between POFUT1 and the above-mentioned tumor tissue matrix score, immune cell infiltration score, and comprehensive score. Further, the String database and GEPIA2 were used to screen POFUT1-related genes, and the functional enrichment analysis of POFUT1 and its related genes was carried out based on the DAVID database. Results Compared with the paired normal tissues，the expression difference of POFUT1 was statistically significant in the cholangiocarcinoma，colon cancer，breast cancer，esophageal cancer，glioblastoma，head and neck squamous cell carcinoma，renal chromophobe carcinoma，low-grade brain glioma，hepatocyte cancer， lung adenocarcinoma，lung squamous cell carcinoma，pancreatic cancer，rectal adenocarcinoma，skin melanoma，gastric cancer，gastroesophageal cancer and thyroid cancer（all P<0. 05）. Seven tumor types showed differential expression of PO⁃ FUT1 in the TIMER2 and GEPIA databases（colon cancer，esophageal cancer，glioblastoma，head and neck squamous cell carcinoma，renal chromophobe carcinoma，rectal adenocarcinoma，and gastric cancer）. In the renal clear cell carcinoma and rectal adenocarcinoma，the overall survival time of the high POFUT1 expression group was higher than that of the low POFUT1 expression group（P<0. 05）. In the low-grade brain glioma，mesothelioma，and uveal melanoma，the overall survival time of low POFUT1 expression group was higher than that of the high POFUT1 expression group（P<0. 05）. The three tumors with the strongest correlation between POFUT1 and immune cell infiltration levels were low-grade glioma，colon cancer，and bladder urothelial carcinoma. The expression level of POFUT1 was related to the stroma，immune cell infiltration and comprehensive score of low-grade brain glioma tissues and the immune infiltration score of colorectal cancer tissues（all P<0. 05）. The enriched pathways of POFUT1 and its related genes were mainly protein binding and RNA binding pathway, serine-related enzyme pathway，apoptosis pathway，and Notch signaling pathway. Conclusions The ex⁃ pression level of POFUT1 increases in 17 types of tumors. Renal clear cell carcinoma and rectal adenocarcinoma with high POFUT1 expression have better prognosis，while low-grade brain glioma，mesothelioma and uveal melanoma with low ex⁃ pression have better prognosis. POFUT1 may affect the prognosis of tumor patients by regulating the level of tumor immune infiltration and signaling pathways such as protein binding，RNA binding and Notch signaling pathway. [ABSTRACT FROM AUTHOR]

NF2 alteration is the most commonly–found genetic abnormality in meningiomas and is known to initiate events for aggressive-type meningiomas. Whereas the prognosis of meningiomas differs depending on their epigenomic/transcriptomic profile, the effect of NF2 alteration on the prognosis of benign meningiomas is not fully elucidated. This study aimed to probe the importance of NF2 alteration in prognosis of WHO grade I meningiomas. A long-term retrospective follow-up (5.3 ± 4.5 years) study involving 281 consecutive WHO grade I meningioma patients was performed. We assessed tumour recurrence in correlation with extent of resection (EOR), histopathological findings, tumour location, and NF2 alteration. "NF2 meningioma" was defined as meningiomas with presence of NF2 mutation and/or 22q loss. Overall, NF2 meningioma per se was not a predictor of prognosis in the whole cohort; however, it was a predictor of recurrence in supratentorial meningiomas, together with EOR and Ki-67. In a striking contrast, NF2 meningioma showed a better prognosis than non-NF2 meningioma in infratentorial lesion. Supratentorial NF2 meningiomas had higher Ki-67 and forkhead box protein M1 expression than those of others, possibly explaining the worse prognosis in this subtype. The combination of NF2 alteration, high Ki-67 and supratentorial location defines subgroup with the worst prognosis among WHO grade I meningiomas. Clinical connotation of NF2 alteration in terms of prognosis of WHO grade I meningioma differs in an opposite way between supratentorial and infratentorial tumors. Integrated anatomical, histopathological, and genomic classifications will provide the best follow-up schedule and proactive measures. [ABSTRACT FROM AUTHOR]

Introduction: TRIpartite motif (TRIM) proteins are important members of the Really Interesting New Gene‐finger‐containing E3 ubiquitin‐conjugating enzyme and are involved in the progression of hepatocellular carcinoma (HCC). However, the diverse expression patterns of TRIMs and their roles in prognosis and immune infiltrates in HCC have yet to be analyzed. Materials: Combined with previous research, we used an Oncomine database and the Human Protein Atlas to compare TRIM family genes' transcriptional levels between tumor samples and normal liver tissues, as verified by the Gene Expression Profiling Interactive Analysis database. We investigated the patient survival data of TRIMs from the Kaplan–Meier plotter database. Clinicopathologic characteristics associations and potential diagnostic and prognostic values were validated with clinical and expressional data collected from the cancer genome atlas. Results: We identified TRIM28, TRIM37, TRIM45, and TRIM59 as high‐priority members of the TRIMs family that modulates HCC. Low expression of TRIM28 was associated with shorter overall survival (OS) than high expression (log‐rank p = 0.009). The same trend was identified for TRIM37 (p = 0.001), TRIM45 (p = 0.013), and TRIM59 (p = 0.011). Multivariate analysis indicated that the level of TRIM37 was a significant independent prognostic factor for both OS (p = 0.043) and progression‐free interval (p = 0.044). We performed expression and mutation analysis and functional pathways and tumor immune infiltration analysis of the changes in TRIM factors. Conclusion: These data suggested that TRIM28, TRIM37, TRIM45, and TRIM59 could serve as efficient prognostic biomarkers and therapeutic targets in HCC. [ABSTRACT FROM AUTHOR]

RNA-binding proteins (RBPs) play pivotal roles in carcinogenesis and immunotherapy. Leucine-rich pentapeptide repeat-containing protein (LRPPRC) is crucial for RNA polyadenylation, transport, and stability. Although recent studies have suggested LRPPRC's potential role in tumor progression, its significance in tumor prognosis, diagnosis, and immunology remains unclear. We comprehensively analyzed LRPPRC expression in tumors using various databases, including Human Transcriptome Cell Atlas (HTCA), University of California Santa Cruz (UCSC), Human Protein Atlas (HPA), Sangerbox, TISIDB, GeneMANIA, GSCALite, and CellMiner. We examined the correlation between LRPPRC expression level and prognosis, immune infiltration, immunotherapy, methylation, biological function, and drug sensitivity. Single-cell analysis was performed using Tumor Immune Single Cell Hub (TISCH) and CancerSEA software. Patients with acute myeloid leukemia (AML) were categorized based on LRPPRC levels for functional and immune infiltration analyses. The role of LRPPRC in cancer was validated using in vitro experiments. Our findings revealed that LRPPRC was highly expressed in almost all cancer types, indicating its significant prognostic and diagnostic potential. Notably, LRPPRC was associated with diverse immune features, such as immune cell infiltration, immune checkpoint genes, tumor mutational burden, and microsatellite instability, suggesting its value in guiding immunotherapy strategies. Within AML, the high-expression group had lower levels of immune cells, including CD8+ T cells. In vitro experiments confirmed the inhibitory effects of LRPPRC knockdown on AML cell proliferation. This study highlights LRPPRC as a reliable pan-cancer prognostic and immune biomarker, particularly in AML. It lays the groundwork for future research on LRPPRC-targeted cancer therapies. [Display omitted] • LRPPRC is highly expressed in almost all cancer types. • LRPPRC exhibits significant prognostic and diagnostic value in most cancers. • LRPPRC significantly correlates with tumor immunity and immunotherapy pan-cancer. • Knockdown of LRPPRC inhibits cell proliferation in AML in vitro. [ABSTRACT FROM AUTHOR]

Solitary fibrous tumors (SFTs) are known for their heterogeneous morphology, characterized by a variety of cell shapes and different growth patterns. They can also arise in various anatomical locations, most commonly in extremities and deep soft tissues. Despite this diversity in morphology and location, all SFTs share a common molecular signature involving the NAB2::STAT6 gene fusion. Due to their unpredictable clinical behavior, establishing prognostic factors is crucial. This study aims to evaluate an orbital risk stratification system (RSS) proposed by Huang et al. for use in extraorbital SFTs using a database of 97 cases. The Huang model takes into consideration tumor size, mitotic figures, Ki-67 index, and dominant constituent cell (DCC) as key variables. Survival analysis confirmed the model's predictive value, with higher-risk scores being associated with poorer outcomes. However, in contrast to the orbital SFTs studied by Huang et al., our study did not find a correlation between tumor size and recurrence in extraorbital cases. While the Huang model performs slightly better than other RSS, it falls short on achieving statistical significance in distinguishing recurrence risk groups in extraorbital locations. In conclusion, this study validates the Huang RSS for use in extraorbital SFTs and underscores the importance of considering DCC, mitotic count, and Ki-67 together. However, we found that including tumor size in this model did not improve prognostic significance in extraorbital SFTs. Despite the benefits of this additional RSS, vigilant monitoring remains essential, even in cases classified as low-risk due to the inherent unpredictability of SFT clinical outcomes. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the predictions of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for prognosis of triple-negative breast cancer (TNBC), especially with residual disease (RD) after preoperative chemotherapy. This retrospective analysis included 74 TNBC patients who received preoperative chemotherapy. DCE-MRI findings from three timepoints were examined: at diagnosis (MRIpre), at midpoint (MRImid) and after chemotherapy (MRIpost). These findings included cancer lesion size, washout index (WI) as a kinetic parameter using the difference in signal intensity between early and delayed phases, and time-signal intensity curve types. Distant disease-free survival was analysed using the log-rank test to compare RD group with and without a fast-washout curve. The diagnostic performance of DCE-MRI findings, including positive predictive value (PPV) for pathological responses, was also calculated. RD without fast washout curve was a significantly better prognostic factor, both at MRImid and MRIpost (hazard ratio = 0.092, 0.098, p < 0.05). PPV for pathological complete remission at MRImid was 76.7% by the cut-off point at negative WI value or lesion size = 0, and 66.7% at lesion size = 0. WI and curve types derived from DCE-MRI at the midpoint of preoperative chemotherapy can help not only assess tumour response but also predict prognosis. [ABSTRACT FROM AUTHOR]

Triple negative breast cancer (TNBC) accounts for about a fifth of all breast cancers and includes a diverse group of cancers. The heterogeneity of TNBC and the lack of target receptors on the cell surface make it difficult to develop specific therapeutic treatments. These aspects cause the high negative prognosis of patients with this type of tumor. The analysis of the molecular profiles of TNBC samples has allowed a better characterization of this tumor, supporting the search for new reliable diagnostic markers. To this end, we have developed a bioinformatic approach to integrate networks of genes differentially expressed in basal breast cancer compared to healthy tissues, with miRNAs able to regulate their expression. We studied the role of these miRNAs in TNBC subtype cell lines. We therefore identified two miRNAs, namely miR-135b and miR-365, with a central role in regulating the altered functional pathways in basal breast cancer. These two miRNAs are differentially expressed in human TNBC immunohistochemistry-selected tissues, and their modulation has been shown to play a role in the proliferation of tumor control and its migratory and invasive capacity in TNBC subtype cell lines. From the perspective of personalized medicine, we managed to modulate the expression of the two miRNAs in organotypic cultures, suggesting their possible use as diagnostic and therapeutic molecules. miR-135b and miR-365 have a key role in TNBC, controlling proliferation and invasion. Their detection could be helpful in TNBC diagnosis, while their modulation could become a new therapeutic tool for TNBC. [ABSTRACT FROM AUTHOR]

Background: The tumor microenvironment is highly heterogeneous, and it is understood to affect tumor progression and patient outcome. A number of studies have reported the prognostic significance of tumor-infiltrating lymphocytes and tumor budding in colorectal cancer (CRC). However, the significance of the intratumoral heterogeneity present in the spatial distribution of these features within the tumor immune microenvironment (TIME) has not been previously reported. Evaluating this intratumoral heterogeneity may aid the understanding of the TIME's effect on patient prognosis as well as identify novel aggressive phenotypes which can be further investigated as potential targets for new treatment. Methods: In this study, we propose and apply two spatial statistical methodologies for the evaluation of the intratumor heterogeneity present in the distribution of CD3 + and CD8 + lymphocytes and tumor buds (TB) in 232 Stage II CRC cases. Getis-Ord hotspot analysis was applied to quantify the cold and hotspots, defined as regions with a significantly low or high number of each feature of interest, respectively. A novel spatial heatmap methodology for the quantification of the cold and hotspots of each feature of interest, which took into account both the interpatient heterogeneity and the intratumor heterogeneity, was further developed. Results: Resultant data from each analysis, characterizing the spatial intratumor heterogeneity of lymphocytes and TBs were used for the development of two new highly prognostic risk models. Conclusions: Our results highlight the value of applying spatial statistics for the assessment of the intratumor heterogeneity. Both Getis-Ord hotspot and our proposed spatial heatmap analysis are broadly applicable across other tissue types as well as other features of interest. [ABSTRACT FROM AUTHOR]

Clival chordoma is a rare disease with high recurrence rates even after a combination of surgical resection and radiotherapy. Apparent diffusion coefficient (ADC) has been used to evaluate aggressive features of chordoma, but its utility for clival chordoma has not been explored specifically. In this study, the utility of preoperative ADC values was analyzed for predicting tumor progression and recurrence in patients with clival chordoma. Between 2012 and 2019, a total of 30 operated cases were analyzed with available preoperative ADC data. Receiver operating characteristic (ROC) analysis was used to obtain ADC cutoff values for predicting tumor aggressiveness. The mean and minimum ADC values were significantly lower in the aggressive tumor group than in the stable tumor group (both P < 0.001). ROC analysis showed that a mean cutoff ADC value of 1198 × 10−6 mm2/s and minimum ADC value of 895.5 × 10–6 mm2/s could be used to predict aggressive features of clival chordoma. Subtotal resection, partial resection, and mean and minimum ADC values that were lower than cutoff values were negative predictors of overall survival and progression-free survival. In conclusion, mean and minimum ADC values could be useful in predicting aggressiveness of clival chordoma. [ABSTRACT FROM AUTHOR]

Background: Breast carcinoma is a common malignant tumor among Iraqi women. In the micro-tumor environment, tumor-associated macrophages (TAMs) are the main ingredients of cells, CD68 is the best sign of TAMs, which is now generally used to predict in several tumors, such as bladder, thyroid, and hepatocarcinoma. Aim: In this study, we highlight the role and significance of the expression of tumor macrophages bearing the CD68 marker in breast cancer development of Iraqi women which may be as a target of therapy in the future. Methods: Fifty samples of paraffin embedded tissue of breast carcinoma from Al-Hussain teaching hospital and private clinical lab were involved for immunohistochemical staining of CD68. Results: Breast cancer has been associated significantly with aging and the advanced degrees of cancer. The expression CD68 + macrophages were highly prevalent in the second and third advanced histological grades compared to the first grade of breast cancer (P <0.001). Conclusions: The expression CD68 is linked with advanced breast cancer grades and may has predictive values for breast cancer among Iraqi women in Thi-Qar province that may have preventative effect via start of chemotherapy for the disease in its early stages. [ABSTRACT FROM AUTHOR]

Background: Vascular endothelial growth factor (VEGF) gene is highly polymorphic, and single nucleotide polymorphisms (SNP) of VEGF gene are associate with cancer prognosis. This study aimed to analyze the correlation of VEGF gene polymorphisms with grade and prognosis of lung cancer. Methods: A total of 458 Chinese patients with primary lung cancer were enrolled from September 2008 to October 2013. The genotypes of −2578C > A, −1154G > A, − 460 T > C, and + 405G > C were analyzed in white blood cells from patients using polymerase chain reaction based restriction fragment length polymorphism. Results: Our data showed that –1154G > A polymorphism was significantly associated with tumor stages, but all four tested VEGF gene polymorphisms had no significant effect on survival. Conclusions: VEGF polymorphisms may relate to stage of lung cancer in Chinese population. [ABSTRACT FROM AUTHOR]

Background: Low-grade gliomas (LGG), approximately constitute one-third of all types of gliomas, are prone to relapse and metastasis. MicroRNA-138 (miR-138) is reported to be dysregulated in diverse human tumors and mainly function as a tumor suppressor. In this study, we analyzed the expression profile and function of miR-138 in LGG. Methods: Quantitative PCR (qPCR) and public database bioinformatics analysis were performed to determine the miR-138 levels in LGG. MiR-138 overexpression in LGG cells was achieved by miR-138 mimics transfection. Cell proliferation was assessed by CCK8, EdU and colony formation assays. Cell invasion and migration were analyzed by transwell and wound-healing assays. Xenograft model was employed to study the role of miR-138 in LGG growth in vivo. The target of miR-138 was validated by multiple methods, such as luciferase reporter assay, RT-qPCR and Western blot. Bioinformatics analysis was conducted to explore the molecular mechanisms by which miR-138 contributed to LGG progression. Results: miR-138 was significantly downregulated in LGG tumor tissues and low expression of miR-138 was significantly associated with poor prognosis as well as relapse and metastasis in LGG patients. Functional analysis indicated that ectopic miR-138 expression suppressed LGG cell growth and invasive phenotype in vitro, and inhibited tumor development in vivo. Moreover, miR-138 directly targeted and repressed insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) by targeting the 3ʹ-UTR of IGF2BP2, inhibiting epithelial to mesenchymal transition (EMT) to attenuate LGG aggressiveness. In addition, we found that elevated IGF2BP2 expression correlates with poor survival of LGG patients. Conclusion: miR-138 may function as a tumor inhibitor by directly inhibiting IGF2BP2 and suppressing EMT in the progression of LGG. [ABSTRACT FROM AUTHOR]

Aim: Small bowel tumors are rare tumors originating from the gastrointestinal tract. In this study, we aimed to determine the clinical characteristics and prognostic factors effecting survival in patients with small bowel cancer. Material and Methods: Eighty patients with small bowel malignancy between February 2002 and December 2016 were evaluated retrospectively. Clinical characteristics, pathological features, laboratory results, progression-free and overall survival rates were determined. The effect of the evaluated parameters on survival was examined. Results: The incidence of small bowel tumors was 0.36% in patients admitted to our clinic. The median age of the patients was 55 and 68.8% of the patients were male. The most common histologic subtype was adenocancer (42.5%), and the most common localization site (37.5%) was duodenum. 27 of patients (33.8%) had metastasis at the time of diagnosis. The most common site of metastasis was liver. Overall survival rate was 59.1% in the third year and 52.9% in the fifth year. The median disease-free survival (DFS) rate was 78% in the third year and 68% in the fifth year. Conclusion: Information about these tumors is limited in the literature and was presented in retrospective case series. In our study, the most common localization site was found as duodenum and the most common histological type was adenocancer. Prognosis of patients undergoing curative surgical resection was found to be better. [ABSTRACT FROM AUTHOR]

Glioblastoma Multiforme (GBM) without IDH mutation has lower overall survival rate, despite having been treated by the standard treatment regimen. Nimotuzumab was expected to improve survival. Expression of EGFR and PD-L1 protein can be used as biomarkers to evaluate the prognosis in patients treated with nimotuzumab. This study aimed to demonstrate the correlation between EGFR and PD-L1 expression with the prognosis (survival rate) of GBM without IDH mutation treated with nimotuzumab. The method of this study are cross-sectional analytic observational study. Total of 26 patients newly diagnosed with GBM without IDH mutation, where 13 were treated with nimotuzumab and 13 were treated without nimotuzumab. EGFR and PDL-1 expression were evaluated using immunohistochemistry. The results is patients treated with nimotuzumab showed significantly higher mean overall survival in comparison with those without treatment (12.23 ± 10.25 vs 6.31 ± 3.33 months, p<0.05). Patients treated with nimotuzumab also showed significantly higher 1- and 2-year survival rate (30.8% vs 15.4% and 7.7% vs 0%, p<0,05). Mean overall survival in the nimotuzumab treatment group was higher in patients with negative in comparison with positive EGFR expression (26.50 ± 24.75 vs 9.64 ± 4.08 months, p>0.05), with negative in comparison with moderate PD-L1 expression (13.80 ± 17.02 vs 11.25 ± 3.41 months, p>0.05). EGFR and PD-L1 expression has not been proven useful as prognostic markers. [ABSTRACT FROM AUTHOR]

Background: The C-reactive protein/albumin (CRP/Alb) ratio has been reported as a prognostic factor of survival for patients with a variety of cancers. However, its prognostic impact for advanced cancer patients receiving palliative care remains presently unknown. Objective: The present study assessed the prognostic value of the CRP/Alb ratio, and compared this with that of the Glasgow Prognostic Score (GPS) and Palliative Prognostic Index (PPI) in a cohort of advanced cancer patients receiving palliative therapy. Methods: The medical records of 262 eligible patients who died of advanced cancer from February 1, 2013 to December 30, 2017 in the palliative care unit of the Fudan University Shanghai Cancer Center were retrospectively reviewed for the analysis. Results: The present results revealed that a CRP/Alb ratio ≥1.31 (hazard ratio [HR], 2.33 [1.78–3.05], p < 0.001) can predict poor prognosis through univariate analysis. In addition, the multivariate analysis revealed that CRP/Alb (HR, 2.09 [1.54–2.84], p < 0.001), GPS (HR, 1.81 [1.07–3.07], p < 0.001), and PPI (HR, 3.35 [2.25–4.99], p < 0.001) were all independent prognosis factors. To compare the discriminatory performance of the CRP/Alb ratio with that of other established prognostic indexes in palliative care settings, the c-statistics, integrated discriminatory improvement index, net reclassification index, and receiver operating characteristic curves were generated, and it was demonstrated that the CRP/Alb ratio (c-statistics, 0.64 [0.61–0.68]) was able to discriminate advanced cancer patients with different survivals, with analogous discriminatory ability as GPS (c-statistics, 0.63 [0.59–0.66]) and PPI (c-statistics, 0.64 [0.60–0.68]). Notably, the combination of multiple prognostic indexes exerted higher discriminatory ability, compared with any single predictive index (c-statistics, 0.69 [0.66–0.73], p < 0.001). Conclusions: The present study suggests that the CRP/Alb ratio is a promising prognostic factor in predicting cancer patient survival in palliative care settings. Incorporating both objective parameters and the subjective index may improve the prediction accuracy of prognosis. [ABSTRACT FROM AUTHOR]

Objective: Immune checkpoint inhibitors (ICIs) for cancer therapy frequently induce immune‐related adverse effects (IRAEs). Therefore, most patients with preexisting autoimmune diseases have been excluded from clinical trials of ICIs. This study was undertaken to evaluate the safety and efficacy of ICIs in patients with preexisting autoimmune disease and cancer. Methods: A retrospective cohort study was conducted from January 2017 to January 2018 via 3 French national networks of experts in oncology and autoimmunity. Adults with preexisting autoimmune disease who were receiving ICIs were assessed for the occurrence of flare of preexisting autoimmune disease, other IRAEs, and cancer response. Results: The study included 112 patients who were followed up for a median of 8 months. The most frequent preexisting autoimmune diseases were psoriasis (n = 31), rheumatoid arthritis (n = 20), and inflammatory bowel disease (n = 14). Twenty‐four patients (22%) were receiving immunosuppressive therapy at ICI initiation. Autoimmune disease flare and/or other IRAE(s) occurred in 79 patients (71%), including flare of preexisting autoimmune disease in 53 patients (47%) and/or other IRAE(s) in 47 patients (42%), with a need for immunosuppressive therapy in 48 patients (43%) and permanent discontinuation of ICI in 24 patients (21%). The median progression‐free survival was shorter in patients receiving immunosuppressive therapy at ICI initiation (3.8 months versus 12 months; P = 0.006), confirmed by multivariable analysis. The median progression‐free survival was shorter in patients who experienced a flare of preexisting autoimmune disease or other IRAE, with a trend toward better survival in the subgroup without immunosuppressant use or ICI discontinuation. Conclusion: Our findings indicate that flares or IRAEs occur frequently but are mostly manageable without ICI discontinuation in patients with a preexisting autoimmune disease. Immunosuppressive therapy at baseline is associated with poorer outcomes. [ABSTRACT FROM AUTHOR]

The article offers information related to prediction of lazarus effects in patients facing cancer. Topics discussed include patients having cancer face multiple stresses like contemplating mortality and accuracy of prognostication, loss of functioning, changing family dynamics and financial strain; and rapid development of new cancer therapies, prognostic uncertainty making more complex for patients and providers.

Immuno-oncology has rapidly grown in the last thirty years, and immunotherapeutic agents are now approved to treat many disparate cancers. Immune checkpoint inhibitors (ICIs) are employed to augment cytotoxic anti-cancer activity by inhibiting negative regulatory elements of the immune system. Modulating the immune system to target neoplasms has improved survivability of numerous cancers in many individuals, but forecasting outcomes post therapy is difficult due to insufficient predictive biomarkers. Recently, the tumor and gastrointestinal microbiome and immune milieu have been investigated as predictors and influencers of cancer immune therapy. In this review, we discuss: (1) ways to measure the microbiome including relevant bioinformatic analyses, (2) recent developments in animal studies and human clinical trials utilizing gut microbial composition and function as biomarkers of cancer immune therapy response and toxicity, and (3) using prebiotics, probiotics, postbiotics, antibiotics, and fecal microbiota transplant (FMT) to modulate immune therapy. We discuss the respective benefits of 16S ribosomal RNA (rRNA) gene and shotgun metagenomic sequencing including important considerations in obtaining samples and in designing and interpreting human and animal microbiome studies. We then focus on studies discussing the differences in response to ICIs in relation to the microbiome and inflammatory mediators. ICIs cause colitis in up to 25% of individuals, and colitis is often refractory to common immunosuppressive medications. Researchers have measured microbiota composition prior to ICI therapy and correlated baseline microbiota composition with efficacy and colitis. Certain bacterial taxa that appear to enhance therapeutic benefit are also implicated in increased susceptibility to colitis, alluding to a delicate balance between pro-inflammatory tumor killing and anti-inflammatory protection from colitis. Pre-clinical and clinical models have trialed probiotic administration, e.g. Bifidobacterium spp. or FMT, to treat colitis when immune suppressive agents fail. We are excited about the future of modulating the microbiome to predict and influence cancer outcomes. Furthermore, novel therapies employed for other illnesses including bacteriophage and genetically-engineered microbes can be adapted in the future to promote increased advancements in cancer treatment and side effect management. [ABSTRACT FROM AUTHOR]

Cancer is a major cause of death worldwide. MET tyrosine kinase receptor [MET, c-MET, hepatocyte growth factor (HGF) receptor] pathway activation is associated with the appearance of several hallmarks of cancer. The HGF/MET pathway has emerged as an important actionable target across many solid tumors; therefore, biomarker discovery becomes essential in order to guide clinical intervention and patient stratification with the aim of moving towards personalized medicine. The focus of this review is on how the aberrant activation of the HGF/MET pathway in tumor tissue or the circulation can provide diagnostic and prognostic biomarkers and predictive biomarkers of drug response. Many meta-analyses have shown that aberrant activation of the MET pathway in tumor tissue, including MET gene overexpression, gene amplification, exon 14 skipping and other activating mutations, is almost invariably associated with shorter survival and poor prognosis. Most meta-analyses have been performed in non-small cell lung cancer (NSCLC), breast, head and neck cancers as well as colorectal, gastric, pancreatic and other gastrointestinal cancers. Furthermore, several studies have shown the predictive value of MET biomarkers in the identification of patients who gain the most benefit from HGF/MET targeted therapies administered as single or combination therapies. The highest predictive values have been observed for response to foretinib and savolitinib in renal cancer, as well as tivantinib in NSCLC and colorectal cancer. However, some studies, especially those based on MET expression, have failed to show much value in these stratifications. This may be rooted in lack of standardization of methodologies, in particular in scoring systems applied in immunohistochemistry determinations or absence of oncogenic addiction of cancer cells to the MET pathway, despite detection of overexpression. Measurements of amplification and mutation aberrations are less likely to suffer from these pitfalls. Increased levels of MET soluble ectodomain (sMET) in circulation have also been associated with poor prognosis; however, the evidence is not as strong as it is with tissue-based biomarkers. As a diagnostic biomarker, sMET has shown its value in distinguishing cancer patients from healthy individuals in prostate and bladder cancers and in melanoma. On the other hand, increased circulating HGF has also been presented as a valuable prognostic and diagnostic biomarker in many cancers; however, there is controversy on the predictive value of HGF as a biomarker. Other biomarkers such as circulating tumor DNA (ctDNA) and tumor HGF levels have also been briefly covered. In conclusion, HGF/MET aberrations can provide valuable diagnostic, prognostic and predictive biomarkers and represent vital assets for personalized cancer therapy. [ABSTRACT FROM AUTHOR]

Background/Aims. Calpain small subunit 1 (Capn4) is implicated in tumorigenesis and plays a key role in multiple tumors. This study aimed to fully illustrate the prognostic value of Capn4 protein in cancer patients. Methods. A systematic search was conducted against several online databases. Hazard ratios (HRs) or odds ratio (ORs) were used to investigate the relationship between Capn4 protein expression and prognosis as well as clinical parameters in cancer survivors. Results. Eleven studies involving 1775 patients were identified. Overall, the results showed that Capn4 protein was associated with poor prognosis of overall survival (OS) (HR=1.74; 95% CI:1.47-2.01; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) in various cancers. And expression of Capn4 protein was related to depth of invasion (OR= 4.17; 95% CI: 1.42-12.27; p=0.01), venous invasion (OR=2.34; 95% CI: 1.07-5.13; p=0.03), lymph node metastasis (2.74; 95% CI: 1.98-3.79; p<0.001), distant metastasis (OR=4.02; 95% CI: 2.14-7.57; p<0.001), and clinical stage (OR=2.87; 95% CI: 1.94-4.26; p<0.001), whereas expression of the Capn4 protein was not associated with gender (OR=1.09; 95% CI: 0.86-1.39; p=0.47) and tumor differentiation (OR=1.16; 95% CI: 0.90-2.23; p=0.25). Conclusions. Expression of Capn4 protein is associated with cancer survival and clinicopathologic characteristics in patients. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are a class of short (~22 nucleotides [nt]), single-stranded RNA oligonucleotides that are regulatory in nature and are often dysregulated in various diseases, including cancer. miRNAs can act as oncomiRs (miRNAs associated with cancer) or tumor suppressor miRNAs and have the potential to be a diagnostic, prognostic, noninvasive biomarker for these diseases. MicroRNA-221 (miR-221) and microRNA-222 (miR-222) are homologous miRNAs, located on the human chromosome Xp11.3, which factored significantly in impairment in the regulation of a wide range of cancers. In this review, we have highlighted the most consistently reported dysregulated miRNAs that trigger human tissues to express cancerous features and surveyed the role of those miRNAs in metastasis, apoptosis, angiogenesis, and tumor prognosis. Also, we applied the causes of drug resistance and the role of coordinated actions of these miRNAs to epigenetic changes and selected miRNAs as a potential type of cancer treatment. [ABSTRACT FROM AUTHOR]

Objective: Little data about the management of drugs in terminally ill palliative care cancer patients is available. The present study aimed at describing the evolution of anticancer and non-anticancer treatments (NACTs) in cancer patients in palliative care units. The second objective was to identify factors leading to the medical decision to withdraw or not NACTs. Methods: Data from 1,091 cancer patients hospitalized in palliative care units were prospectively collected in 2010–2011, through a multicenter, observational French cohort. Results: The median overall survival after admittance in palliative care units was 15 days. Specific anticancer treatments were systematically stopped in the first 24 h in palliative care units, but for 4.5% of patients. Regarding NACTs, patients were heavily treated with strong opioids (74%), corticosteroids (51%), and antidepressants (21.8%) until death. Antiulcer agents (63.4%), antibiotics (25.7%), thrombosis prevention (21.8%), antidiabetics (7.6%), and transfusions (4%) were often also continuously prescribed. In multivariate analysis, ECOG PS 4 was an independent predictor of continuous prescription of morphine and an independent predictor of discontinuation of corticosteroids, proton-pump inhibitors, antidiabetics, and preventive anticoagulant therapy. Infection symptoms independently predicted continuous prescription of paracetamol. Paralysis and cancer palpable mass independently predicted corticosteroid withdrawal. Brain metastases independently predicted antiulcer withdrawal. Hemorrhage independently predicted preventive anticoagulant withdrawal. Availability to a venous access independently predicted paracetamol and antiulcer continuous prescriptions. Co-prescriptions independently predicted continuous prescriptions (antibiotics with antiulcer, antifungals with antibiotics) or withdrawal (preventive anticoagulant with antiplatelets and antifungals). Conclusions: NACT prescription remained commonplace in terminally ill palliative cancer patients, although their benefit is questionable. [ABSTRACT FROM AUTHOR]

Background: Cancer is the first cause of death in developed countries. The heterogeneous nature of cancer requires patient-specified treatment plans. One reliable approach is collecting Circulating Tumour Cells (CTCs) and using them for prognosis and drug response assessment purposes. CTCs are rare and their separation from normal cell requires high-accuracy methods. Methods: A microfluidic cell capture device to separate CTCs from peripheral blood is presented in this study. The CTC separation device applies hydrodynamic forces to categorize cells according to their sizes. The proposed device is designed and evaluated by numerical simulations and validated experimentally. The simulation modified design was fabricated by soft lithography which allows prototyping the device in a few hours. For experimental setup two solutions: 1) fixed cells spiked in Phosphate Buffered Saline (PBS), and 2) fixed cells in blood were used. The CTC separation device was validated by tracking the flow and separation of cancer cell lines in the solutions. Results: It is demonstrated that the setup is capable of CTC enrichment up to 50 times. Conclusion: The presented CTC enrichment method reduces costs by eliminating the use of antibodies. The high-throughput method has the potential to be used in preclinical studies of cancer. [ABSTRACT FROM AUTHOR]

PURPOSE: This study (1) assesses the level of clinical work intensity medical oncologists and oncologic nurse practitioners experience providing care and (2) identifies patient, provider, and practice factors mediating intensity. PATIENTS AND METHODS: Seventeen medical oncologists (12 physicians and five nurse practitioners) from five national sites national reported on the level of work intensity associated with 339 patient visits. Data collection at each site occurred over a 2- to 6 week period; for each provider, five visits were randomly selected from each of 4 randomly selected clinic days, yielding 20 visits per provider. Intensity was measured by the NASA–Task Load Index. Patient and visit characteristics were abstracted from the medical record; provider characteristics were self-reported by questionnaire. RESULTS: Clinical work intensity increased monotonically with level of service and was greatest when the visit involved discussion of either chemotherapy or terminal prognosis. Provider characteristics (including age, sex, and years of experience) were unrelated to intensity. Dimensions of work intensity that correlated directly with level of service included mental, physical, and temporal demand; effort; frustration; and stress. Perceptions of performance and of satisfaction with the visit were unrelated to level of service. Visits related to chemotherapy had greater mental, physical, and temporal demand, and effort, but worse perception of performance. When the visit involved a discussion of a terminal prognosis, greater intensity was reflected in all dimensions; stress was also greater, whereas visit satisfaction was significantly lower. CONCLUSION: Clinical work intensity increases with level of service provided and is greater for visits involving discussion of either terminal prognosis or chemotherapy. [ABSTRACT FROM AUTHOR]

PURPOSE: Immunotherapy has rapidly become the mainstream treatment of multiple cancer types. Since the first drug approval in 2011, we have noted a decline in referrals from inpatient oncology to hospice and an increase in referrals to subacute rehabilitation (SAR) facilities, possibly with the aim of getting strong enough for immunotherapy and other promising drugs. This study explores outcomes after discharge to SAR, including rates of cancer-directed therapy after SAR, overall survival, and hospice use. METHODS: We performed an electronic chart review of patients discharged from our inpatient oncology units to SAR facilities from 2009 to 2017. Demographics, admission statistics, and post-discharge outcomes were gathered from discharge summaries and targeted chart searches. RESULTS: Three hundred fifty-eight patients were referred to SAR 413 times. One hundred seventy-four patients (49%) returned to the oncology clinic before readmission or death, and only 117 (33%) ever received additional cancer-directed treatment (chemotherapy, radiation, or immunotherapy). Among all discharges, 28% led to readmissions within 30 days. Seventy-four patients (21%) were deceased within 30 days, only 31% of whom were referred to hospice. Palliative care involvement resulted in more frequent do not resuscitate code status, documented goals of care discussions, and electronic advance directives. CONCLUSION: A growing number of oncology inpatients are being discharged to SAR, but two thirds do not receive additional cancer therapy at any point, including a substantial fraction who are readmitted or deceased within 1 month. These data can help guide decision making and hospital discharge planning that aligns with patients' goals of care. More clinical data are needed to predict who is most likely to benefit from SAR and proceed to further cancer therapy. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to analyze the survival outcomes of stage IIIC ovarian high‐grade serous carcinoma (HGSC) patients with both peritoneal and lymphatic dissemination (IP+/RP+) who had undergone maximal or optimal cytoreduction followed by intravenous carboplatin/paclitaxel chemotherapy compared to those women with stage IIIC ovarian HGSC with only peritoneal involvement (IP+/RP−) who were treated similarly. Methods: We performed a retrospective, multicenter study with the participation of five gynecological cancer centers. First, the stage IIIC ovarian HGSC patients were classified into optimally or maximally debulked cohorts. Then, in each cohort, the patients were divided into two groups; the IP+/RP− group included those women with transcoelomic spreading outside the pelvis with no nodal disease, and the IP+/RP+ group included those patients with transcoelomic dissemination outside the pelvis in addition to a positive nodal status. The survival outcomes were compared between the two groups in each cohort. Results: A total of 405 ovarian HGSC patients were analyzed. In the optimally debulked cohort (n = 257), the progression‐free survival (PFS) and overall survival (OS) medians for the IP+/RP− group (n = 69) were 24 and 57 months, respectively, compared to 21 and 58 months, respectively, for the IP+/RP+ group (n = 188) (P = 0.78 and P = 0.40, respectively). In the maximally debulked cohort (n = 148), the PFS and OS medians for the IP+/RP− group (n = 55) were 35 and 63 months, respectively, compared to 25 and 51 months, respectively, for the IP+/RP+ group (n = 93) (P = 0.49 and P = 0.31, respectively). Conclusion: Our findings indicated no survival differences between the IP+/RP− and the IP+/RP+ groups. [ABSTRACT FROM AUTHOR]

Background: Although palliative care is expanding globally for patients with serious illness, Turkey has not had widespread integration of early concurrent oncology palliative care. Hence, adapting and testing models of concurrent oncology palliative care for Turkish patients is imperative. Furthermore, it is critical that these care models also address the needs of family caregivers. Objective: To assess needs and elicit suggestions that would inform the adaptation of the ENABLE (Educate, Nurture, Advise, Before Life Ends) evidence-based early palliative care model for Turkish family caregivers of older persons with cancer. Methods: Formative evaluation study. Semi-structured interviews were conducted with 25 primary family caregivers of older individuals with cancer. Thematic analyses yielded themes in four domains: meaning of caregiving, effect of caregiving, education and consulting needs, and preferences about the delivery of the ENABLE model of palliative care support. Results: Caregivers described the impact of the cancer on their daily lives and responsibilities in the areas of physical, psychological, work, social, and family life. Caregivers emphasized their needs for information about symptoms, physical care, cancer pathology, and prognosis. Regarding the ENABLE model of early concurrent palliative care, participants wanted encounters to be in-person with educational material support that was simple and focused on disease information (prognosis, medication, handling emergency situations), psychological support, caring, nutrition, and acquiring community services. Conclusion: Themes from this study will be used to modify the ENABLE intervention protocol for future pilot and efficacy testing in Turkish caregivers. [ABSTRACT FROM AUTHOR]

For a person to enter a Dutch hospice as resident, a clearly articulated deadline is needed: a life expectancy of three months or less. This paper argues that this institutional timeframe of a singular, clock-timed period of more or less linearly approaching death (the end of time), affords life to unfold in hospice as a relatively clockless multitude of temporal orderings enacted by staff and residents (the time of the end). Based on a period of ethnographic fieldwork in hospices and focusgroup interviews with hospice staff, I analyse how temporal orderings manifest and intersect in different ways. The quality of these intersections presence end-of-life normativities in ways that may be instructive when designing and reflecting on end-of-life care. [ABSTRACT FROM AUTHOR]

Background: Routine imaging ("scan") results contain key prognostic information for advanced cancer patients. Yet, little is known about how accurately patients understand this information, and whether psychological states relate to accurate understanding. Objective: To determine if patients' sadness and anxiety, as well as results showing poorer prognosis, are associated with patients' understanding of scan results. Design: Archival contrasts performed on multi-institutional cohort study data. Subjects: Advanced cancer patients whose disease progressed after at least one chemotherapy regimen (N = 94) and their clinicians (N = 28) were recruited before an oncology appointment to discuss routine scan results. Measurements: In preappointment structured interviews, patients rated sadness and anxiety about their cancer. Following the appointment, patients and clinicians reported whether the imaging results discussed showed progressive, improved, or stable disease. Results: Overall, 68% of patients reported their imaging results accurately, as indicated by concordance with their clinician's rating. Accuracy was higher among patients whose results indicated improved (adjusted odds ratio [AOR] = 4.12, p = 0.02) or stable (AOR = 2.59, p = 0.04) disease compared with progressive disease. Patients with greater anxiety were less likely to report their imaging results accurately than those with less anxiety (AOR = 0.09, p = 0.003); in contrast, those with greater sadness were more likely to report their results accurately than those with less sadness (AOR = 5.23, p = 0.03). Conclusions: Advanced cancer patients with higher anxiety and those with disease progression may need more help understanding or accepting their scan results than others. [ABSTRACT FROM AUTHOR]

The purpose of this systematic review was to identify validated nutritional screening tools for cancer patients. The research was conducted in the electronic databases Pubmed, Cochrane Library, Scopus, and Biblioteca Virtual de Saúde (BVS), using the descriptors "Nutrition Assessment", "Neoplasms", and "Validation studies". Initially, we identified 168 articles. After assessing eligibility, we included 21 studies. In selected studies, 14 nutritional screening tools were validation objects. The Patient-Generated Subjective Global Assessment (PG-SGA) showed better sensitivity, specificity and positive and negative predictive values (98, 82, 95, and 93%, respectively), as well as predictive of overall survival in cancer patients. In many countries, in addition to PG-SGA, the Nutrition Risk Screen (NRS-2002) is recommended for these patients. We did not identify, however, manuscripts that proposed validation. Validation studies of nutritional screening tools should be performed on patients with cancer, using representative samples of these individuals for better reliability of their results. [ABSTRACT FROM AUTHOR]

Chinese medicine therapies in cancer treatment are very common in the East. Although it is usually classified as a form of complementary and alternative therapy in the West, Chinese medicine is an independent medical profession in Hong Kong and mainland China. It has a different perspective in understanding health and diseases compared with Western medicine. In oncology practice, whereas Western medicine focuses on direct tumour eradication by surgery, radiation therapy and systemic therapies, Chinese medicine focuses on restoring body balance and enhancing the body's defences (immunity), in addition to some cytotoxic herbal therapies. Most often patients, especially those in the East, receive both treatments. Chinese medicine is also commonly used to reduce side-effects from chemotherapy or radiation therapy, to aid recovery after an operation, to palliate symptoms and to address survivorship issues. However, this raises concerns of drug–herb interactions and toxicity in combination therapies. Commonly used Chinese medicine treatment modalities include acupuncture, moxibustion, diet therapy, prescribed Chinese medicine herbal decoction, single Chinese medicine herbs or supplements and tai chi. Although there is an increasing trend of Chinese medicine use in cancer patients in both the East and the West, the scientific evidence of safety and efficacy is often questioned by oncologists. This article reviews the current evidence in different Chinese medicine therapies in cancer management in both the East and the West. [ABSTRACT FROM AUTHOR]

Background: Terminally ill cancer patients' worsening symptom distress and functional impairment may signal disease deterioration, thus facilitating their accurate prognostic awareness (PA). However, the joint roles played by symptom distress and functional impairment in association with cancer patients' accurate PA remain unexplored. Methods: We used hierarchical generalized linear modeling to assess associations between our five identified worsening conjoint symptom-functional states and accurate PA in a convenience sample of 317 terminally ill cancer patients over their last six months. Results: The majority of our participants (70.1%–76.3%) had accurate PA in their last six months. This proportion did not increase as death approached but varied significantly by the five identified distinct symptom-functional states. Participants in the four worst symptom-functional states (moderate/profound symptom distress with mild/profound functional impairment) had a higher likelihood of accurate PA than those in the best state (mild symptom distress with high functioning). Participants with severe or profound symptom distress (states 3 and 5) had a substantially higher likelihood of accurate PA than those with moderate symptom distress (states 2 and 4). Conclusion/Clinical Implications: Terminally ill cancer patients' five distinct conjoint worsening symptom-functional states were differentially associated with their likelihood of accurate PA. Health care professionals should cultivate these patients' accurate PA when they are still free from severe symptom distress and functional impairment, effectively manage symptoms for those suffering from severe/profound symptom distress, and facilitate their psychological-spiritual adjustment to acknowledge their poor prognosis and the accompanying challenges of end-of-life care decisions to maximize quality of life and achieve a good death. [ABSTRACT FROM AUTHOR]

Background: Little is known about how immigration status influences preference for life-extending care (LEC) at the end of life (EoL). Objective: The purpose was to determine how preference for LEC at the EoL for advanced cancer patients varied by Latino ethnicity and immigrant status, and over time between two large cohorts. Methods: Data were derived from two sequential multi-institutional, longitudinal cohort studies of advanced cancer patients, recruited from 2002 to 2008 (coping with cancer I [CwC-1]) and 2010 to 2015 (coping with cancer II [CwC-2]). Self-reported U.S.-born whites (whites) (N = 253), U.S.-born Latinos (US-L) (N = 34), and Latino immigrants (LI) (N = 65) with a poor-prognosis cancer were included. The primary independent variables were immigrant status, Latino ethnicity, and CwC cohort. The primary dependent variable was preference for LEC. Results: Within CwC-2, LI were 9.4 times more likely to prefer LEC over comfort care versus US-L (adjusted odds ratio [AOR] = 9.4; 95% confidence interval [CI]: 1.2–72.4), and US-L were 0.3 times less likely to prefer LEC versus whites (AOR = 0.3; 95% CI: 0.1–1.0). LI from CwC-2 were 11.4 times more likely to prefer LEC versus LI from CwC-1 (AOR = 11.4; 95% CI: 2.7–48.4). Within CwC-1, there was no difference in LEC preference between LI and US-L, nor between US-L and whites. Conclusions: Immigrant status had a strong effect on preference for LEC at the EoL among the more recent cohort of Latino cancer patients. Preference for LEC appears to have increased significantly over time for LI but remained unchanged for US-L. LI may increasingly want LEC near death. [ABSTRACT FROM AUTHOR]

Background: The objective of this observational study is to determine the changes in the circulating immune cells as a predictor of outcomes in patients who have survived cancer. Materials and Methods: A peripheral blood immune-profile evaluation was performed in all the survivors of cancer (n = 66) during their visit to the hospital for regular follow-up and thereafter followed up for two consecutive years for any morbidity or mortality. The changes in hematological and biochemical parameters were evaluated in all the patients. The frequency of circulating lymphocyte cell population i.e., CD3+, CD4+, and CD8+ lymphocytes were analyzed using flow cytometry in the peripheral blood of the patients. The variability in the circulating lymphocytes was correlated with tumor relapse and overall survival (OS). Results: In the study, 47 of the 66 patients with cancer survived at the end of 2 years observation time period, while 19 patients died due to infection related complications and not due to tumor relapse. A significant reduction in the neutrophil (P < 0.0001) and lymphocyte (P < 0.0001) counts were observed in patients who succumbed to the illness within 2 years when compared to the cohorts that were surviving. A statistically significant reduction in the absolute lymphocyte counts (P < 0.004), absolute CD3 (P < 0.0001), CD4 (P < 0.002), and CD8 (P < 0.04) were observed in the deceased group compared to the surviving group. CD4/CD8 ratios between both live and deceased groups did not show any significant difference. Conclusion: This preliminary observational study indicates a correlation of circulatory lymphocytes to OS in survivors of cancer and that it could be a predictive marker. [ABSTRACT FROM AUTHOR]

Background. Inducible nitric oxide synthase (iNOS) is confirmed to regulate the production of nitric oxide (NO) when cells are exposed to external stimulus. Recent publications revealed that overexpression of iNOS predicted poor clinical outcomes for patients with malignant cancers, e.g., gastric, bladder, and colorectal cancers; however, several studies reported no obvious relationship between iNOS expression and prognosis of solid tumors. The aim of our study was to investigate the pooled effect of the prognostic value of iNOS expression. Materials and Methods. We performed a systematic search of PubMed, Web of Science, and Embase databases up to January 15, 2019. The concerned outcomes of interest included overall survival (OS), cancer-special survival (CSS), and recurrence-free survival (RFS). Results. Fourteen studies with 1,758 patients were included in this meta-analysis, and we reached the conclusion that increased iNOS expression was significantly associated with worse OS (HR: 1.89, 95% CI: 1.57 - 2.28, p ≤ 0.001), worse CSS (HR: 3.13, 95% CI: 1.88 - 5.20, p ≤ 0.001), and worse RFS (HR: 2.16, 95% CI: 1.29 - 3.62, p = 0.003) in solid tumors. Furthermore, the subgroup analysis identified the significant relationship of high iNOS expression with poor OS in gastric cancer. No obvious publication bias was detected by Begg's tests. Conclusion. In summary, the results drawn in our meta-analysis demonstrated that elevated expression of iNOS had a significant association with poor survival in human cancer. iNOS might serve as a promising predictive biomarker of prognosis in cancer patients, and well-designed prospective studies are further needed to substantiate the prognostic value of iNOS. [ABSTRACT FROM AUTHOR]

Background: Neoplastic pericardial effusion (NPE) is a life-threatening condition that can worsen clinical outcome in cancer patients. The optimal management of NPE has yet to be defined because randomized studies are lacking. Objective: We report a retrospective monoinstitutional experience describing characteristics, management and prognostic factors in NPE patients. Design: We reviewed clinical, pathological, and echocardiographic features, therapeutic strategies, and outcome in NPE patients referred to our institute from August 2011 to December 2017. Measurements: Twenty-nine patients with NPE from solid tumors have been identified: 21 lung, 5 breast, and 3 other cancer patients. Results: Median age was 62 years. Most of the patients had Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2 (69%) and a symptomatic NPE (69%). In 52% of patients NPE was detected at first diagnosis of metastatic disease, and in 20% of patients pericardium was the only site of metastases. Most of the patients (62%) received systemic therapy, 28% received combined locoregional and systemic therapy, and 10% received locoregional therapy alone. Median overall survival (OS) from NPE diagnosis was 3.9 months. Patients with PS ≥2 had worse OS than patients with better PS <2 (hazard ratio [HR] 3.56, IC 95% 1.19–10.65, p 0.02). Older age, extrapericardial disease, and NPE at progression showed a trend of association with worse OS. Patients treated with locoregional therapy alone showed the shortest median OS (p 0.05). Conclusions: NPE is related to dismal prognosis. Poor PS significantly worsens survival and influences therapeutic approaches. Randomized studies are required to investigate prognostic factors and appropriate clinical management for patients with NPE. [ABSTRACT FROM AUTHOR]

Background: There is no established method to objectively predict short-term prognosis. Recently, we proposed objective, short-term, prognostic predictive methods that are combinations of laboratory test items: WPCBAL score, derived from six values (white blood cell, platelet, C-reactive protein, blood urea nitrogen, aspartate aminotransferase, and lactate dehydrogenase). However, that study was conducted in an acute-phase hospital to identify the test items useful for prognostic prediction; thus, whether WPCBAL score could be applied to terminal cancer patients in a palliative care unit was unverified. Objective: To verify the usefulness of WPCBAL score for terminal cancer patients. Design: A retrospective study. Setting/Subjects: Patients admitted to the palliative care unit of Ashiya Municipal Hospital (N = 128) in Japan in 2016. Measurements: The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the receiver operating characteristic curve (AUROC) were compared between WPCBAL score and the Glasgow prognostic score (GPS). Results: For predicting three-week prognosis, WPCBAL score showed higher AUROC compared with GPS (0.7540 and 0.6573, respectively). WPCBAL score predicting two-week prognosis showed greater AUROC than GPS predicting three-week prognosis (0.7491 and 0.6573, respectively). Conclusion: WPCBAL score was verified to objectively predict the two- or three-week prognosis for terminal cancer patients in a palliative care unit. WPCBAL score may be a new option for prognostic prediction for terminal cancer patients. [ABSTRACT FROM AUTHOR]

Background: Patients with advanced malignancies have historically been considered poor candidates for admission to the intensive care unit (ICU); however, prognosis is continually improving, and requirements for ICU access are increasing. Aim: To understand the characteristics and outcomes of oncology unit patients admitted to an Australian ICU and identify potential prognostic factors. Methods: A single‐centre, retrospective, cohort study conducted at a tertiary public hospital with a quaternary ICU in Sydney, Australia. All patients admitted under the medical oncology team requiring ICU admission between June 2014 and June 2016 were evaluated. Clinical outcomes were determined including mortality, ICU requirements (ventilation, dialysis, vasopressors, infection) and prognostic scores (Acute Physiologic and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) score). Results: There were 96 patients with mean age 61 years, 58% were male and 76% had metastatic disease. Most were receiving palliative treatment (89%), with recent chemotherapy (43%), immunotherapy (10%) and other therapies (5%). Of the 10 patients with recent immunotherapy, three (all with melanoma) required ICU admission due to immunotoxicity; 13% were admitted due to an oncological emergency. Mean APACHE II score was 17 (standard deviation (SD) 5.33), mean SOFA score was 3.99 (SD 2.70), ICU mortality was 5% and hospital mortality was 22%. Using multivariate logistic regression analysis, cancer stage, infection during ICU admission, intracranial mass effect on ICU admission and SOFA score were associated with 30‐day mortality. Conclusion: Our patient population had good short‐term survival outcomes despite most receiving palliative treatment. Cancer patients can achieve positive outcomes after ICU admission, and appropriate selection of patients is crucial. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. Purpose: This article reviews and updates the evidence on the associations between physical activity and risk for cancer, and for mortality in persons with cancer, as presented in the 2018 Physical Activity Guidelines Advisory Committee Scientific Report. Methods: Systematic reviews of meta-analyses, systematic reviews, and pooled analyses were conducted through December 2016. An updated systematic review of such reports plus original research through February 2018 was conducted. This article also identifies future research needs. Results: In reviewing 45 reports comprising hundreds of epidemiologic studies with several million study participants, the report found strong evidence for an association between highest versus lowest physical activity levels and reduced risks of bladder, breast, colon, endometrial, esophageal adenocarcinoma, renal, and gastric cancers. Relative risk reductions ranged from approximately 10% to 20%. Based on 18 systematic reviews and meta-analyses, the report also found moderate or limited associations between greater amounts of physical activity and decreased all-cause and cancer-specific mortality in individuals with a diagnosis of breast, colorectal, or prostate cancer, with relative risk reductions ranging almost up to 40% to 50%. The updated search, with five meta-analyses and 25 source articles reviewed, confirmed these findings. Conclusions: Levels of physical activity recommended in the 2018 Guidelines are associated with reduced risk and improved survival for several cancers. More research is needed to determine the associations between physical activity and incidence for less common cancers and associations with survival for other cancers. Future studies of cancer incidence and mortality should consider these associations for population subgroups, to determine dose–response relationships between physical activity and cancer risk and prognosis, and to establish mechanisms to explain these associations. [ABSTRACT FROM AUTHOR]

Objective and Background: Survival predictions by subjective evaluations are important for end-stage patients. However, subjective evaluations based on experience are difficult. Therefore, we investigated whether the Glasgow prognostic score (GPS), prognostic nutritional index (PNI), and C-reactive protein (CRP)/albumin ratio (CRP/Alb ratio) calculated from the laboratory values of objective evaluations are useful for predicting survival times in end-stage patients. Methods: We retrospectively investigated the age, sex, death cause, CRP levels, Alb levels, and lymphocyte counts in 363 cancer and noncancer patients who died in the 12-month period between April 2015 and March 2016. A multivariate analysis was performed to calculate GPS, PNI, and the CRP/Alb ratio from laboratory values and adjusted for confounding factors. Results: PNI and CRP/Alb ratio exhibited negative and positive correlations with survival days, respectively. All GPS, PNI, and CRP/Alb ratio were useful to predict two to four remaining weeks. Interestingly, CRP/Alb ratio, but not GPS or PNI, was higher in patients with predicted short-term survival of zero to two weeks than in that of two to four weeks (odds ratio 2.32; 95% confidence interval 1.61–3.34). Discussion: These results suggest that the CRP/Alb ratio is an independent factor that is beneficial to predict short-term survival of within two weeks. [ABSTRACT FROM AUTHOR]

Background: Palliative care is often underutilized or initiated late in the course of life-threatening illness. Randomized clinical Early Palliative Care (EPC) trials provide an opportunity for changing oncologists' perceptions of palliative care and their attitudes to referring patients to palliative care services. Aim: To describe French oncologists' perceptions of EPC and their effects on referral practices before a clinical EPC trial was launched. Design: A qualitative study involving semistructured face-to-face interviews. The data were analyzed using the Grounded Theory coding method. Setting/Participants: Thirteen oncologists and 19 palliative care specialists (PCSs) working at 10 hospitals all over France were interviewed. Most of them were involved in clinical EPC trials. Results: The findings suggest that referral to PCSs shortly after the diagnosis of advanced cancer increases the terminological barriers, induces avoidance patterns, and makes early disclosure of poor prognosis harder for oncologists. This situation is attributable to the widespread idea that palliative care means terminal care. In addition, the fact that the EPC concept is poorly understood increases the confusion between EPC and supportive care. Conclusion: Defining the EPC concept more clearly and explaining to health professionals and patients what EPC consists of and what role it is intended to play, and the potential benefits of palliative care services could help to overcome the wording barriers rooted in the traditional picture of palliative care. In addition, training French oncologists how to disclose "bad news" could help them cope with the emotional issues involved in referring patients to specialized palliative care. [ABSTRACT FROM AUTHOR]