Survival Time Of Cancer Patients Research Articles

Highlights of This Issue

Chen and Zhang and colleagues describe a systematic analysis of molecular correlates of metastasis using The Cancer Genome Atlas (TCGA) datasets across 11 different cancer types, with data involving mRNA, microRNA, protein, and DNA methylation. While some differential expression patterns associated with metastasis may be shared across multiple cancer types, each one also shows a metastasis signature that is distinct. When combining TCGA data with that from multiple independent profiling datasets of metastatic tumors, the resulting catalog of gene-level alterations, according to cancer type, provides a resource for future studies.Cytotoxic T lymphocytes (CTL) use the Fas-mediated apoptosis pathway as one of the two effector mechanisms to suppress tumors. Xiao et al. report here that the CD133+CD24loFaslo colon cancer cell subset exhibits decreased sensitivity to FasL-induced apoptosis in vitro and increased resistance to both tumor-specific CTL adoptive transfer and PD-1 blockade antibody immunotherapies in preclinical mouse tumor models in vivo. Furthermore, Fas expression level is positively correlated with colon cancer patient survival time. This study indicates that the CD133+CD24loFaslo colon cancer cells may, at least in part, underlie colon cancer resistance to immune checkpoint inhibitor immunotherapy.Protocadherins (PCDHs) are transmembrane proteins and members of the Cadherin superfamily that play well-established roles in cell adhesion and regulation of signaling pathways. Both oncogenic and tumor suppressive roles have been assigned to PCDHs. However, the roles of individual PCDHs in cancer and the mechanisms through which their gain-of-function and loss-of-function drive tumorigenesis in vivo remain poorly understood. The current study establishes a critical oncogenic function for PCDH7 in lung cancer using a novel transgenic mouse model. Moreover, somatic genome editing of Pcdh7 with CRISPR/Cas9 in KrasLSL-G12D; Tp53fl/fl mice support the potential therapeutic efficacy of PCDH7 inhibition for patients with lung cancer.Prostate cancer can develop resistance to anti-androgen therapy by reactiving Androgen Receptor (AR) signaling. The critical processes that lie downstream of AR and contribute to tumor growth and therapeutic resistance remain to be fully defined. Zennami and colleagues identified PDCD4, a tumor suppressive protein, as a key target of AR signaling in prostate cancer cells. AR signaling suppresses PDCD4 expression, through miR-21, leading to enhanced cell proliferation, survival, tumorigenesis, and castration resistance. These results uncover PDCD4 loss as a new molecular mechanism of castration resistance and suggest that pathways downstream of PDCD4 may be novel targets for therapy.

Biomarkers with Potential Predictive Value for Cardiotoxicity in Anticancer Treatments.

Rapid development of anticancer treatments in recent years has greatly improved prognosis of cancer patients. However, with extension of survival time of cancer patients, various short-term and long-term side effects brought about by anticancer treatments, especially cardiotoxicity, have become increasingly prominent. Nonetheless, at present, there is few diagnostic methods with extremely high sensitivity and specificity to detect and accurately predict whether patients with anticancer treatment will experience cardiovascular complications. Inflammation, fibrosis and oxidative stress are considered to be important mechanisms involved in cardiotoxicity anticancer treatments. The cardiovascular biomarkers having the ability to predict and detect cardiovascular dysfunction earlier than clinical symptoms as well as left ventricular ejection fraction monitored by echocardiography, are of great value to timely treatment adjustment and prognosis evaluation. Cardiac troponin T/I and brain natriuretic peptide/N-terminal prohormone of brain natriuretic peptide have been routinely used in clinical practice to monitor cardiotoxicity, and some new biomarkers such as soluble suppression of tumorigenecity-2, myeloperoxidase, growth differentiation factor-15, galectin-3, endothelin-1, have potential in this area. In the future, larger-scale experimental studies are needed to provide sufficient evidences, and how to detect them quickly and at low cost is also a problem to be dealed with.

Assessing the Impact of Prognostic Factors on the Survival Time of Cancer Patients: Cox Proportional Hazard Model

Assessing the Impact of Prognostic Factors on the Survival Time of Cancer Patients: Cox Proportional Hazard Model

TP53 mutations as potential prognostic markers for specific cancers: analysis of data from The Cancer Genome Atlas and the International Agency for Research on Cancer TP53 Database.

Mutations in the tumor suppressor gene TP53 are associated with a variety of cancers. Therefore, it is important to know the occurrence and prognostic effects of TP53 mutations in certain cancers. Over 29,000 cases from the April 2016 release of the International Agency for Research on Cancer (IARC) TP53 Database were analyzed to determine the distribution of germline and somatic mutations in the TP53 gene. Subsequently, 7,893 cancer cases were compiled in cBioPortal for Cancer Genomics from the 33 most recent The Cancer Genome Atlas (TCGA) studies to determine the prevalence of TP53 mutations in cancers and their effects on survival and disease-free survival times. The data were analyzed, and it was found that the majority of TP53 mutations were missense and the major mutational hotspots were located at codons 248, 273, 175, and 245 in exons 4-8 for somatic mutations with the addition of codon 337 and other mutations in exons 9-10 for germline mutations. Out of 33 TGCA studies, the effects of TP53 mutations were statistically significant in nine cancers (lung adenocarcinoma, hepatocellular carcinoma, head and neck squamous cell carcinoma, acute myeloid leukemia, clear cell renal cell carcinoma (RCC), papillary RCC, chromophobe RCC, uterine endometrial carcinoma, and thymoma) for survival time and in five cancers (pancreatic adenocarcinoma, hepatocellular carcinoma, chromophobe RCC, acute myeloid leukemia, and thymoma) for disease-free survival time. It was also found that the most common p53 mutation in hepatocellular carcinomas (R249S) was a much better indicator for poor prognosis than TP53 mutations as a whole. In addition, in cases of ovarian serous cystadenocarcinoma, the co-occurrence of TP53 and BRCA mutations resulted in longer survival and disease-free survival times than the presence of neither TP53 nor BRCA mutations. TP53 mutations are potential prognostic markers that can be used to further improve the accuracy of predicting survival and disease-free survival times of cancer patients.

Mo1132 CLINICAL AND ENDOSCOPIC FEATURES OF METASTASES TO THE GASTROINTESTINAL TRACT

Occurrence of metastasis to the gastrointestinal tract (GIT) is rare. The studies on the endoscopic findings of metastatic tumors are usually restricted to small case series. As a consequence of the improved in the survival time for cancer patients over recent years, it is expected that progressively more cancer patients could present for diagnosis, by endoscopy, of secondary tumors of the GIT. With this regard, it would be useful to better characterize the endoscopic aspects of metastases to the GIT. observational study conducted in an oncological referral center between January 2009 and August 2017. The study included patients with metastasis to the GIT, submitted to endoscopic exam (upper gastrointestinal endoscopy, colonoscopy, enteroscopy, endoscopic ultrasound) with histological confirmation. Patients with lymphoma, leukemia, multiple myeloma, Kaposi sarcoma or direct invasion from adjacent organs were excluded. From January 2009 to august 2017, 53.675 endoscopic exams were performed. A total of 184 cases were suspected gastrointestinal metastasis. In 94 patients the diagnosis was confirmed. The baseline characteristics of the patients are summarized in Table 1. Common indications for endoscopy were abdominal pain (29 cases – 30.8%), gastrointestinal bleeding (28 cases – 29.8%) and vomiting (18 cases – 19.1%). The most common site of metastasis was the stomach (60 cases – 59.6%), followed by small bowel (29 cases – 29.8%) and colon (7 cases – 7.4%). Eight patients (8.5%) had metastasis in more than one site in the GIT. As indicated in Table 2, the most common primary malignancy was melanoma (25 cases – 26.6%), followed by breast (14 cases – 14.9%) and lung (14 cases – 14.9%). If considered just the gastric metastasis, the most common primary malignancy was melanoma (17 cases – 28.3%), breast (11 cases - 18.3 %) and lung (7 -11.3%). The most common endoscopic presentation of the metastatic lesions in the stomach was a solitary (32 cases – 53.3 %), ulcerated (31 cases – 51.6%) lesion located in the gastric body (75%). If considered just the small bowel metastasis the most common primary malignancy was lung (7 cases – 24.1%) and melanoma (7 cases – 24.1%) followed by breast (3 cases – 10.4%). The most common endoscopic presentation of the metastatic lesions in small bowel was the presence of a solitary (22 cases 84.6 %), polypoid (10 cases – 38.5%) lesion located in the second portion of duodenum (17 cases – 65.4%). Melanoma, breast and lung cancer were the most common metastasis to the GIT. The stomach was the main site of the metastatic lesions and the most common endoscopic presentation of stomach metastasis was solitary, ulcerated lesions in the gastric body. Despite the rarity of this condition, endoscopists should be aware of this differential diagnosis.Tabled 1Table 1 - Patients CharacteristicsNumber of patientsMale4952.1%Age (years)58.523 - 85Symptoms8388.3 %Dysphagia1111.7 %Weight Loss1313.8 %Bleeding2829.8 %Abdominal pain2930.8 %Nausea or vomiting1819.1 %Jaundice11.1 %Constipation11.1 %Asymptomatic1111.7 %Primary TumorNumber of patient%Head and neck55.3 %Esophagus55.3 %Uterus44.2 %Stomach55.3 %Breast1414.9 %Melanoma2526.6 %Ovary33.2 %Colorectal44.2 %Lung1414.9 %Kidney55.3 %Sarcoma33.2 %Merkel’s tumor11.1 %Duodenum11.1 %Indeterminate site11.1 %Hepatocellular11.1 % Open table in a new tab Tabled 1Table 2 – Endoscopic featuresOrganNumber of patients%Esophagus55.3 %Stomach6059.6 %Small Bowel2930.8 %Colorectal77.4 %Number of metastasisNumber of patients%Single6265.6 %2- 4 lesions1617.1 %> 5 lesions1718,1 %Size< 20mm3335.1 %20 - 50mm4042.5 %> 50mm2122.3 %AspectPolypoid2526.6 %Infiltrative2122.3 %Resembling early cancer1010.63 %Subepitelial33.19 %Ulcerated1718.1 %Ulcero-Infiltrative1819.4 % Open table in a new tab

Multi-omics facilitated variable selection in Cox-regression model for cancer prognosis prediction.

New developments in high-throughput genomic technologies have enabled the measurement of diverse types of omics biomarkers in a cost-efficient and clinically-feasible manner. Developing computational methods and tools for analysis and translation of such genomic data into clinically-relevant information is an ongoing and active area of investigation. For example, several studies have utilized an unsupervised learning framework to cluster patients by integrating omics data. Despite such recent advances, predicting cancer prognosis using integrated omics biomarkers remains a challenge. There is also a shortage of computational tools for predicting cancer prognosis by using supervised learning methods. The current standard approach is to fit a Cox regression model by concatenating the different types of omics data in a linear manner, while penalty could be added for feature selection. A more powerful approach, however, would be to incorporate data by considering relationships among omics datatypes. Here we developed two methods: a SKI-Cox method and a wLASSO-Cox method to incorporate the association among different types of omics data. Both methods fit the Cox proportional hazards model and predict a risk score based on mRNA expression profiles. SKI-Cox borrows the information generated by these additional types of omics data to guide variable selection, while wLASSO-Cox incorporates this information as a penalty factor during model fitting. We show that SKI-Cox and wLASSO-Cox models select more true variables than a LASSO-Cox model in simulation studies. We assess the performance of SKI-Cox and wLASSO-Cox using TCGA glioblastoma multiforme and lung adenocarcinoma data. In each case, mRNA expression, methylation, and copy number variation data are integrated to predict the overall survival time of cancer patients. Our methods achieve better performance in predicting patients' survival in glioblastoma and lung adenocarcinoma.

High expression of long non-coding RNA NEAT1 indicates poor prognosis of human cancer.

The nuclear paraspeckle assembly transcript 1 (NEAT1) is a long non-coding RNA. Many studies have reported that NEAT1 plays critical oncogenic roles and facilitates tumorigenesis of various human cancers. High NEAT1 expression is associated with a poor prognosis in cancer patients. This meta-analysis was conducted to assess the association between NEAT1 levels and survival times of cancer patients. Overall survival (OS) was the primary endpoint. Thirteen publications with 1,496 cancer patients from 5 databases (PubMed, EMBASE, Cochrane Library, Wiley Online Library, and Medline) met the criteria for this meta-analysis. Results of the analysis showed that NEAT1 expression in human cancer was significantly associated with OS (hazard ratio [HR]=1.53, 95% confidence interval [CI]: 1.39–1.68), including digestive system tumor (HR=1.54, 95% CI: 1.37–1.73) and respiratory carcinomas (HR=1.44, 95% CI: 1.11–1.85). The results also indicated that NEAT1 expression was highly associated with tumor size (>3 cm vs. ≤3 cm; odds ratio [OR]=2.51, 95% CI: 1.27–4.99; p=0.009), TNM stage (III+IV vs. I+II; OR=4.17, 95% CI: 2.42–7.18; p=0.00001), and distant metastasis (OR=2.73, 95% CI: 1.28–5.79; p=0.01). However, there was no significant association with differentiation (poor vs. well + moderate, OR=1.45, 95% CI: 0.72–2.91) and lymph node metastasis (OR=1.39, 95% CI: 0.54–3.60). This meta-analysis showed that NEAT1 expression may be a useful biomarker for predicting a poor prognosis in patients with cancer.

Quelle démarche d’éducation thérapeutique (ETP) pour les adolescents et jeunes adultes atteints de cancer ? Expérience du groupe ETP de « Go-AJA »

Therapeutic education (TE) is a practice developed over 40years at an international level to give people with chronic illness the skills necessary to help them better manage their disease. The lengthening survival time of cancer patients as well as changes in the patient-caregiver relationship have contributed to the development of TE in oncologic diseases. Every year in France, about 1900adolescents and young adults (15-25years old) are diagnosed with cancer which is the second leading cause of death in this age group. The observed survival rates for these patients are lower when compared with children's. Some of the hypotheses put forward to explain this difference include a lack of constancy in care and a non-following treatment, as failure to adhere to therapies is common in this age group. "Go-AJA", an interdisciplinary national organization established in 2012, aims to improve the quality of care and treatment results for AYA living with cancer. Therapeutic education for AYA in oncology is an active working group of "Go-AJA" and intends to draw recommendations and to improve adapted communication on different education topics. Elaboration and preparation of TE programs by skilled multidisciplinary teams engaged in interactive educational actions is the first and most crucial step. The TE "Go-AJA" working group has federated pediatric and adult oncologists, nurses, psychologists, TE professionals, and resource patients, thanks to the commitment of professionals from the 8 national teams supported by the National Cancer Institute. Physical meetings and conference calls were organized from 2012 to 2015 to construct TE tools and programs for AYA with cancer. A competence referential was built and adapted to AYA population with cancer, after focused groups organized in 2main oncology centers with on-therapy sarcoma patients and members of the multidisciplinary TE working group. Tools were validated and adapted to adolescents or young adults with cancer, to help in the 4stages of TE: the "educational diagnosis" allowing the caregiver to better understand the patient in his life journey with the disease; the "therapeutic alliance" allowing to agree with the patient on his/her priorities; the "implementation" which is an action step: information, awareness, learning and psychosocial support. The final step called "assessment" allows the caregiver to take stock on the changes and difficulties with the patient. TE for AYA with cancer included individual and/or group sessions to improve self-care skills: knowledge about the disease (group sessions "what is cancer?" with use of microscopes to visualize sarcoma cells, and guided tours in a tumor research laboratory), and details about the treatment and its consequences (workshops about "management of febrile neutropenia"). Moreover, TE aimed to enrich the field of coping skills, in particular to improve the coordination and experience of cares between the different complex and varied network of care (group and/or individual sessions focused on physical rehabilitation, and adapted school/professional orientation). Regardless of the care system, care workers dedicated to AYA with cancer should use TE-specific actions to reinforce treatment participation and therapeutic relationships. This active multidisciplinary TE working group dedicated to AYA with cancer elaborated TE programs by skilled multidisciplinary teams engaged in interactive educational actions. After this work of a national TE organization, more studies using methodological tools are still required to evaluate the impact of such implemented programs on the treatment results and the quality of life.

Blocking hepatic metastases of colon cancer cells using an shRNA against Rac1 delivered by activatable cell-penetrating peptide.

Hepatic metastasis is one of the critical progressions of colon cancer. Blocking this process is key to prolonging survival time in cancer patients. Studies on activatable cell-penetrating peptides (dtACPPs) have demonstrated their potential as gene carriers. It showed high tumor cell-targeting specificity and transfection efficiency and low cytotoxicity in the in vitro settings of drug delivery. However, using this system to silence target genes to inhibit metastasis in colorectal cancer cells has not been widely reported and requires further investigation. In this study, we observed that expression of Rac1, a key molecule for cytoskeletal reorganization, was higher in hepatic metastatic tumor tissue compared with prime colon cancer tissue and that patients with high Rac1-expressing colon cancer showed shorter survival time. Base on these findings, we created dtACPP-PEG-DGL (dtACPPD)/shRac1 nanoparticles and demonstrated that they downregulated Rac1 expression in colon cancer cells. Moreover, we observed inhibitory effects on migration, invasion and adhesion in HCT116 colorectal cancer cells in vitro, and our results showed that Rac1 regulated colon cancer cell matrix adhesion through the regulation of cytofilament dynamics. Moreover, mechanically, repression of Rac1 inhibiting cells migration and invasion by enhancing cell to cell adhesion and reducing cell to extracellular matrix adhesion. Furthermore, when atCDPPD/shRac1 nanoparticles were administered intravenously to a HCT116 xenograft model, significant tumor metastasis to the liver was inhibited. Our results suggest that atCDPP/shRac1 nanoparticles may enable the blockade of hepatic metastasis in colon cancer.

Predictive value of XPG rs2296147T>C polymorphism on clinical outcomes of cancer patients.

The Xeroderma pigmentosum complementation group G (XPG) rs2296147T>C polymorphism is suspected to associate with the clinical outcomes of cancer patients. However, the results are inconsistent. This meta-analysis aimed to evaluate the reliable predictive value of XPG rs2296147T>C polymorphism on clinical outcomes of cancer patients. A total of 11 eligible studies were enrolled in this meta-analysis. Our results indicated that the cancer patients with TT and CT genotypes were significantly associated with better respond rates when compared with the CC genotype (TT versus (vs.) CC: odds ratio (OR) = 2.05, 95% confidence intervals (CIs), 1.32-3.20, P = 0.002; TT+CT vs. CC: OR= 1.57, 95% CI, 1.14-2.17, P = 0.005). The TT genotype and/or T allele might be associated with higher survival time for cancer patients than the CC genotype and/or C allele. The cumulative meta-analyses showed an apparent beneficial objective response of TT genotype on cancer patients. In conclusion, this meta-analysis suggests that the XPG rs2296147T>C polymorphism is associated with the clinical outcomes of cancer patients. The XPG rs2296147T>C polymorphism might be a predictive factor of prognosis in cancers patients and contribute to individual treatment in the future.

Molecular Targeted Therapies for the Treatment of Leptomeningeal Carcinomatosis: Current Evidence and Future Directions.

Leptomeningeal carcinomatosis (LMC) is the multifocal seeding of cerebrospinal fluid and leptomeninges by malignant cells. The incidence of LMC is approximately 5% in patients with malignant tumors overall and the rate is increasing due to increasing survival time of cancer patients. Eradication of the disease is not yet possible, so the treatment goals of LMC are to improve neurologic symptoms and to prolong survival. A standard treatment for LMC has not been established due to low incidences of LMC, the rapidly progressing nature of the disease, heterogeneous populations with LMC, and a lack of randomized clinical trial results. Treatment options for LMC include intrathecal chemotherapy, systemic chemotherapy, and radiation therapy, but the prognoses remain poor with a median survival of <3 months. Recently, molecular targeted agents have been applied in the clinic and have shown groundbreaking results in specific patient groups epidermal growth factor receptor (EGFR)-targeted therapy or an anaplastic lymphoma kinase (ALK) inhibitor in lung cancer, human epidermal growth factor receptor 2 (HER2)-directed therapy in breast cancer, and CD20-targeted therapy in B cell lymphoma). Moreover, there are results indicating that the use of these agents under proper dose and administration routes can be effective for managing LMC. In this article, we review molecular targeted agents for managing LMC.

Predicting Mean Survival Time from Reported Median Survival Time for Cancer Patients.

Mean duration of survival following treatment is a prerequisite for cost-effectiveness analyses used for assessing new and costly life-extending therapies for cancer patients. Mean survival time is rarely reported due to censoring imposed by limited follow-up time, whereas the median survival time often is. The empirical relationship between mean and median survival time for cancer patients is not known. To derive the empirical associations between mean and median survival time across cancer types and to validate this empirical prediction approach and compare it with the standard approach of fitting a Weibull distribution. We included all patients in Norway diagnosed from 1960 to 1999 with one of the 13 most common solid tumor cancers until emigration, death, or 31 December 2011, whichever came first. Observed median, restricted mean, and mean survival times were obtained in subcohorts defined by patients' sex, age, cancer type, and time period of diagnosis, which had nearly complete follow-up. Based on theoretical considerations, we fitted a linear relationship between observed means and medians on the log scale. For validation, we estimated mean survival from medians of bootstrap samples with artificially induced censoring and compared with fitting a Weibull distribution. A linear relationship between log-mean survival time and log-median survival time was identified for the 6 cancers with shortest survival plus metastasized breast and prostate cancers. The predicted means of the empirical approach had smaller bias than the standard Weibull approach. For cancer diagnoses with poor prognosis, mean survival times could be predicted from corresponding medians. This empirical prediction approach is useful for validation of estimates of mean survival time and sensitivity analyses in settings with aggregated data only.

Long non-coding RNA UCA1 is a predictive biomarker of cancer.

Human urothelial carcinoma associated 1 (UCA1) is a long noncoding RNA that is putatively oncogenic in solid tumors. This meta-analysis investigated an association between UCA1 levels and survival times of cancer patients. The primary endpoints were overall survival (OS) and progression-free survival (PFS). A comprehensive, computerized literature search was conducted of the databases PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and Wanfang. The strength of association between UCA1 and cancer prognosis was assessed by computing the hazard ratio (HR) with its corresponding 95% confidence interval (CI). Twelve studies comprising 954 cancer patients met the criteria for this meta-analysis. Overall, a significant negative association was found between UCA1 levels and OS time (HR1.81, 95% CI1.52−2.17), including the following cancers analyzed independently: colorectal (HR2.61, 95% CI1.56−4.37), non-small cell lung (HR1.49, 95% CI1.16−1.90), gastric (HR2.19, 95% CI1.36−3.51), and ovarian (HR1.89, 95% CI1.14−3.12). There was also a significant negative association between UCA1 levels and PFS time (HR2.59, 95% CI1.61−4.16). In conclusion, this meta-analysis indicated that higher levels of UCA1 correlate with shorter PFS and OS times in cancers.

Cancer rehabilitation in Austria—aspects of Physical Medicine and Rehabilitation

In Austria, cancer rehabilitation is an important issue in the management of cancer patients. Survival rates and survival time of cancer patients are increasing, and cancer rehabilitation is an important part in the treatment and care of cancer patients with the goal to improve functional status, quality of life, and (social) participation. Today, in Austria there are approximately 600 beds for inpatient rehabilitation. The field of outpatient rehabilitation will maybe be expanded after evaluating the existing pilot projects. Beside other specialities, the field of Physical Medicine and Rehabilitation (PM&R) plays an important role in cancer rehabilitation. In cancer rehabilitation, especially activating modalities from PM&R such as exercise are very important and well-accepted parts to improve functional status, quality of life, and participation of patients.

Mining gene link information for survival pathway hunting.

This study proposes a gene link-based method for survival time-related pathway hunting. In this method, the authors incorporate gene link information to estimate how a pathway is associated with cancer patient's survival time. Specifically, a gene link-based Cox proportional hazard model (Link-Cox) is established, in which two linked genes are considered together to represent a link variable and the association of the link with survival time is assessed using Cox proportional hazard model. On the basis of the Link-Cox model, the authors formulate a new statistic for measuring the association of a pathway with survival time of cancer patients, referred to as pathway survival score (PSS), by summarising survival significance over all the gene links in the pathway, and devise a permutation test to test the significance of an observed PSS. To evaluate the proposed method, the authors applied it to simulation data and two publicly available real-world gene expression data sets. Extensive comparisons with previous methods show the effectiveness and efficiency of the proposed method for survival pathway hunting.

Palliative Vitamin C Application in Patients with Radiotherapy-Resistant Bone Metastases: A Retrospective Study

The aim of this study was to observe effects of ascorbic acid application on pain, performance status, and survival time in cancer patients. A retrospective cohort of 39 patients with bone metastases treated with radiotherapy was identified. All patients were radiotherapy-resistant. Fifteen patients who received chemotherapy, and 15 patients who received an infusion of 2.5 g ascorbic acid were included in the study. Nine control patients were treated with neither chemotherapy nor vitamin C. Eastern Cooperative Oncology Group Performance Status Scale and Visual Analog Scale were used to determine performance status and pain assessments. Survival time and rate in patients were defined. Statistical analyses were performed to compare the results of groups. Performance status was increased in 4 patients of vitamin C group and 1 patient of chemotherapy group, whereas performance status in control group was decreased. A median reduction of 50% in pain was observed among the patients in the vitamin C group. Median survival time was 10 mo in patients receiving ascorbic acid, whereas the chemotherapy and control groups had a median survival of 2 mo. Intravenous vitamin C application seems to reduce pain in patients in comparison to other patients who did not receive it. Patient performance status and survival rate were increased using vitamin C.

Association of Depression and Survival in Patients with Cancer over 10 Years

Purpose: This study was conducted to identify the effects of depression on the survival of patients with cancer over a 10 year period. Methods: A retrospective review was conducted to examine survival of 218 patients with stomach, colorectal and breast cancer, who had been treated for cancer from 2002 to 2011. Depression was assessed by using the Symptom Check List-90 Revision in 2002, and hope, fighting spirit and other potential confounders were also measured to control for their effects on the association between depression and the survival time. Data on survival were collected from the Statistics Korea and also from medical record in 2011. Kaplan-Meier survival analysis and Cox proportional hazard regression model were used to examine if depression affected survival. Results: The total number of death was 106, and the non-survivors scored higher on depression than survivors. Depression was found to be one of the influencing factors on survival from cancer. Conclusion: Depression was significantly associated with the increased risk of death in cancer patients. Further research is needed to identify in details which type of emotional interventions can extend the survival time of cancer patients in depression.

E2F4 regulatory program predicts patient survival prognosis in breast cancer.

IntroductionGenetic and molecular signatures have been incorporated into cancer prognosis prediction and treatment decisions with good success over the past decade. Clinically, these signatures are usually used in early-stage cancers to evaluate whether they require adjuvant therapy following surgical resection. A molecular signature that is prognostic across more clinical contexts would be a useful addition to current signatures.MethodsWe defined a signature for the ubiquitous tissue factor, E2F4, based on its shared target genes in multiple tissues. These target genes were identified by chromatin immunoprecipitation sequencing (ChIP-seq) experiments using a probabilistic method. We then computationally calculated the regulatory activity score (RAS) of E2F4 in cancer tissues, and examined how E2F4 RAS correlates with patient survival.ResultsGenes in our E2F4 signature were 21-fold more likely to be correlated with breast cancer patient survival time compared to randomly selected genes. Using eight independent breast cancer datasets containing over 1,900 unique samples, we stratified patients into low and high E2F4 RAS groups. E2F4 activity stratification was highly predictive of patient outcome, and our results remained robust even when controlling for many factors including patient age, tumor size, grade, estrogen receptor (ER) status, lymph node (LN) status, whether the patient received adjuvant therapy, and the patient’s other prognostic indices such as Adjuvant! and the Nottingham Prognostic Index scores. Furthermore, the fractions of samples with positive E2F4 RAS vary in different intrinsic breast cancer subtypes, consistent with the different survival profiles of these subtypes.ConclusionsWe defined a prognostic signature, the E2F4 regulatory activity score, and showed it to be significantly predictive of patient outcome in breast cancer regardless of treatment status and the states of many other clinicopathological variables. It can be used in conjunction with other breast cancer classification methods such as Oncotype DX to improve clinical outcome prediction.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-014-0486-7) contains supplementary material, which is available to authorized users.

Predicting Survival Time in Noncurative Patients with Advanced Cancer: A Prospective Study in China

Accurate prediction of prognosis for cancer patients is important for good clinical decision making in therapeutic and care strategies. The application of prognostic tools and indicators could improve prediction accuracy. This study aimed to develop a new prognostic scale to predict survival time of advanced cancer patients in China. We prospectively collected items that we anticipated might influence survival time of advanced cancer patients. Participants were recruited from 12 hospitals in Shanghai, China. We collected data including demographic information, clinical symptoms and signs, and biochemical test results. Log-rank tests, Cox regression, and linear regression were performed to develop a prognostic scale. Three hundred twenty patients with advanced cancer were recruited. Fourteen prognostic factors were included in the prognostic scale: Karnofsky Performance Scale (KPS) score, pain, ascites, hydrothorax, edema, delirium, cachexia, white blood cell (WBC) count, hemoglobin, sodium, total bilirubin, direct bilirubin, aspartate aminotransferase (AST), and alkaline phosphatase (ALP) values. The score was calculated by summing the partial scores, ranging from 0 to 30. When using the cutoff points of 7-day, 30-day, 90-day, and 180-day survival time, the scores were calculated as 12, 10, 8, and 6, respectively. We propose a new prognostic scale including KPS, pain, ascites, hydrothorax, edema, delirium, cachexia, WBC count, hemoglobin, sodium, total bilirubin, direct bilirubin, AST, and ALP values, which may help guide physicians in predicting the likely survival time of cancer patients more accurately. More studies are needed to validate this scale in the future.

Meta-analysis of the effects of beta blocker on survival time in cancer patients

This study was to elucidate the potential benefit of beta blockers on cancer survival. We comprehensively searched PubMed, Embase, and the Cochrane Library from their inception to April 2013. Two authors independently screened and reviewed the eligibility of each study and coded the participants, treatment, and outcome characteristics. The primary outcomes were overall survival (OS) and disease-free survival (DFS). Twelve studies published between 1993 and 2013 were included in the final analysis. Four papers reported results from 10 independent groups, resulting in a total of 18 comparisons based on data obtained from 20,898 subjects. Effect sizes (hazard ratios, HR) were heterogeneous, and random-effects models were used in the analyses. The meta-analysis demonstrated that beta blocker use is associated with improved OS (HR 0.79; 95 % CI 0.67-0.93; p = 0.004) and DFS (HR 0.69; 95 % CI 0.53-0.91; p = 0.009). Although statistically not significant, the effect size was greater in patients with low-stage cancer or cancer treated primarily with surgery than in patients with high-stage cancer or cancer treated primarily without surgery (HR 0.60 vs. 0.78, and 0.60 vs. 0.80, respectively). Although only two study codes were analyzed, the studies using nonselective beta blockers showed that there was no overall effect on OS (HR 0.52, 95 % CI 0.09-3.04). This meta-analysis provides evidence that beta blocker use can be associated with the prolonged survival of cancer patients, especially patients with early-stage cancer treated primarily with surgery.