Survival In Metastatic Cancer Research Articles

Promising Directions: A Systematic Review of Psychosocial and Behavioral Interventions with Cultural Incorporation for Advanced and Metastatic Cancer.

Improving quality of life (QOL) in advanced and metastatic cancer is a priority with increasing survivorship. This systematic review synthesizes psychosocial and behavioral interventions incorporating culture with the goal of examining their benefit for understudied and medically underserved populations with advanced and metastatic cancer. Reports were systematically screened for (1) a focus on advanced and metastatic cancer survivors, (2) psychosocial or behavioral intervention intended to improve QOL, (3) evidence of incorporating the culture(s) of understudied/underserved populations, and (4) availability in English. Bias was evaluated using the JBI Critical Appraisal Checklist and the Methodological index for non-randomized studies. Qualitative synthesis and quantitative meta-analyses were completed. Eighty-six reports containing 5981 participants' data were examined. Qualitative synthesis of 23 studies identified four overarching themes relevant for incorporating culture in interventions. Meta-analysis of 19 RCTs and 4 quasi-experimental studies containing considerable heterogeneity indicated greater improvements in QOL (g = 0.84), eudaimonic well-being (g = 0.53), distress (g = -0.49), and anxiety (g = -0.37) for main intervention conditions compared to controls. Meta-analysis of 10 single-arm trials containing minimal to moderate heterogeneity found benefit for anxiety (g = -0.54), physical symptoms (g = -0.39), and depression (g = -0.38). Psychosocial and behavioral interventions with cultural incorporation appear beneficial for improving QOL-related outcomes in advanced and metastatic cancer. Studies incorporating culture in psychosocial or behavioral interventions offer noteworthy insight and suggestions for future efforts such as attending to deep cultural structure.

Causes of death among people living with metastatic cancer

Studying survivorship and causes of death in patients with advanced or metastatic cancer remains an important task. We characterize the causes of death among patients with metastatic cancer, across 13 cancer types and 25 non-cancer causes and predict the risk of death after diagnosis from the diagnosed cancer versus other causes (e.g., stroke, heart disease, etc.). Among 1,030,937 US (1992–2019) metastatic cancer survivors, 82.6% of patients (n = 688,529) died due to the diagnosed cancer, while 17.4% (n = 145,006) died of competing causes. Patients with lung, pancreas, esophagus, and stomach tumors are the most likely to die of their metastatic cancer, while those with prostate and breast cancer have the lowest likelihood. The median survival time among patients living with metastases is 10 months; our Fine and Gray competing risk model predicts 1 year survival with area under the receiver operating characteristic curve of 0.754 (95% CI [0.754, 0.754]). Leading non-cancer deaths are heart disease (32.4%), chronic obstructive and pulmonary disease (7.9%), cerebrovascular disease (6.1%), and infection (4.1%).

POSA391 Real-World Long-Term Overall Survival in Metastatic Cancer in Sweden

POSA391 Real-World Long-Term Overall Survival in Metastatic Cancer in Sweden

Experience and supportive care needs of metastatic lung cancer survivors living with uncertainty: a brief qualitative report.

Molecularly targeted therapies have revolutionized non-small cell lung cancer (NSCLC) treatment. Many patients with metastatic NSCLC receiving targeted therapy may live several years with incurable cancer. We sought to describe how these metastatic cancer survivors and their caregivers experience uncertainty about the future and identify their unmet supportive care needs. We conducted semi-structured interviews with patients with metastatic NSCLC receiving targeted therapy (n = 39) and their caregivers (n = 16). We used a framework approach to code and analyze the qualitative data. Metastatic lung cancer survivors described awareness of their mortality and the possibility that their cancer could progress at any time. Though some found ways to cope, many felt inadequately supported to manage their distress, especially since they were "doing fine medically." Survivors struggled with decisions about working and managing their finances given their uncertain life expectancy and sought trustworthy lung cancer information in plain language. They wished to compare experiences with other patients with their molecular subtype of NSCLC. Participants desired comprehensive cancer care that includes psychosocial support, preparation for the future, and ways to promote their own health, such as through lifestyle changes. Patients with metastatic NSCLC receiving targeted therapy and their caregivers experience distress related to living with uncertainty and desire more coping support, connection with peers, information, and healthy lifestyle guidance. Patients living with treatable yet incurable cancer and their caregivers are a growing population of cancer survivors. Recognition of their unmet needs may inform the development of tailored support services to help them live well with cancer.

Clinical results after biliary drainage by endoscopic retrograde cholangiopancreatography for analysis of metastatic cancer survival and prognostic factors.

Malignant biliary obstruction secondary to metastatic cancer is associated with poor prognosis. To the best of our knowledge, no previous study has investigated long-term survival and associated prognostic factors after biliary endoscopic retrograde cholangiopancreatography (ERCP) drainage for obstruction jaundice secondary to various types of metastatic cancer. This retrospective study included 60 patients who underwent biliary ERCP drainage for obstructive jaundice secondary to metastatic cancer at two hospitals during the period from November 2012 to December 2019. Multivariate analysis was conducted to identify independent prognostic factors. Biliary drainage was successfully achieved in 55 (91.7%) patients, 37 of whom received subsequent treatment. Overall median survival time was 133days after stent placement. The overall survival (OS) rates after ERCP drainage were significantly better in the post-drainage treatment group than in the post-drainage untreated group (239days vs. 45days, p < 0.001). Good ECOG performance status before drainage, albumin level ≥ 35g/L, successful drainage, absence of ascites, and post-drainage treatment were identified as factors of improved survival in univariate analysis. ECOG performance status and post-drainage treatment were independent predictors of OS in multivariate analysis. We showed that stent placement with ERCP was a safe and effective treatment method for patients with malignant biliary obstruction caused by metastatic cancer and may be preferred over percutaneous transhepatic biliary drainage. Post-drainage treatment and a good ECOG performance status were predictors of better prognosis.

Abstract 4349: Comparison of Psychosocial Wellbeing among African American and Caucasian Metastatic Cancer Survivors

Abstract Introduction: Approximately 5 million Americans are living with metastatic cancer and are at an increased risk for psychosocial distress (e.g., hopelessness). Hope is vital to life and is essential for effectively coping with illness. Among early-stage cancer survivors, previous studies indicate that African Americans (AA) experience greater cancer burden than Caucasians (CAU). The aim of this study was to compare psychosocial wellbeing between AA and CAU MCS residing in the Deep South. Methods: MCS were identified via UAB Cancer Registry and I2B2.Using a modified Dilman's method, eligible MCS (&amp;gt;21 years and physician permission to contact) were mailed a survey. Psychosocial wellbeing (i.e. physical and mental wellbeing, anxiety, depression, social isolation, emotional support, and hopefulness) of MCS were assessed via PROMIS® measures. Returned surveys were double-key entered into REDCap®. Data were analyzed using Excel. Descriptive statistics were used to characterize the study sample and instrument scores. Between group difference, between AA and CAU MCS, was examined via independent-samples t-test. Results: To date, 100 surveys have been returned (AA=18; CAU=82; Mage=67 years; Msurvivorship=3 years) with a broad representation of primary cancer sites (breast=23%; prostate=10%; gynecological=16%; colorectal=13%; lung=10%; kidney=11%; other=17%). Mean instrument scores were similar between AA and CAU MCS for physical wellbeing (44.57 vs 44.81), mental wellbeing (48.1 vs 48.46), anxiety (45.76 vs 48.45), depression (44.85 vs 46.77), social isolation (39.96 vs 40.89), and emotional support (39.96 vs 40.89). However, AA MCS reported significantly better feelings of hopefulness than CAU MCS (61.34 vs 55.39, p&amp;gt;0.01, d=0.73). Discussion: Findings suggest that AA MCS may be more hopeful than CAU MCS. These preliminary findings warrant further analysis after data collection is complete (an additional 300 returned surveys are anticipated). Citation Format: Jayla M. Caffey, Jennifer Bail. Comparison of Psychosocial Wellbeing among African American and Caucasian Metastatic Cancer Survivors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4349.

CAM-Delam: an in vivo approach to visualize and quantify the delamination and invasion capacity of human cancer cells

The development of metastases is the major cause of cancer related death. To develop a standardized method that define the ability of human cancer cells to degrade the basement membrane, e.g. the delamination capacity, is of importance to assess metastatic aggressiveness. We now present the in vivo CAM-Delam assay to visualize and quantify the ability of human cancer cells to delaminate and invade. The method includes seeding cancer cells on the chick chorioallantoic membrane (CAM), followed by the evaluation of cancer-induced delamination and potential invasion within hours to a few days. By testing a range of human cancer cell lines in the CAM-Delam assay, our results show that the delamination capacity can be divided into four categories and used to quantify metastatic aggressiveness. Our results emphasize the usefulness of this assay for quantifying delamination capacity as a measurement of metastatic aggressiveness, and in unraveling the molecular mechanisms that regulate delamination, invasion, formation of micro-metastases and modulations of the tumor microenvironment. This method will be useful in both the preclinical and clinical characterization of tumor biopsies, and in the validation of compounds that may improve survival in metastatic cancer.

Value of oncologist generated “surprise question” in predicting survival in metastatic cancer.

12082 Background: Treating patients with metastatic cancer (MCA) requires timely integration of palliative and hospice care (PHC). The Surprise Question (SQ-“Would you be surprised if your patient died in the next year?”) may help predict short-term mortality in patients with chronic disease and prompt initiation of PHC. There limited data on the utility of the SQ in oncology and none controlling for age and cancer site (CS). This study evaluates the SQ in MCA. Methods: SQ data were collected using a clinical oncology pathway program (COP) in which the treating oncologist is required to answer the SQ for all patients with MCA. The cohort includes MCA patients with SQ entries from 5-1-2018 to 4-30-2019 providing cohorts with 6- and 12-months follow-up (f/u) from the date of the SQ. Vital status was determined as of 1-15-20. Over 90% of deaths are reported with 3 months of death. Models using SQ response (yes/no), cancer site and age were tested with logistic regression (LR) with Akaike Information Criterion (AIC) for model selection (lower number best model) and ANOVA to assess the value of the SQ in predicting mortality. Results: There were 655 and 1276 patients with MCA in COP with 1 year and 6 months f/u from the SQ, respectively. The proportion with the SQ response “No” (shorter expected survival) varied by cancer site (range 19% – 82% - e.g. breast 42%; pancreas 81%). The SQ was the best predictor compared to cancer site and age for 6 and 12-month mortality (LR Model A – lowest AIC). The odds ratio of death at one year from SQ-No vs. SQ-Yes was 3.8 (95% CI 2.7, 5.4) with a strong association between SQ response and 1-year and 6-month mortality (p &lt; 0.001). See Table. Conclusions: Oncologist assessment of survival expectancy by the SQ in MCA is a strong predictor of mortality beyond cancer site and age. The treating oncologist’s response to SQ can serve as a simple and reliable predictive tool to identify those with MCA likely to die sooner who may benefit from timely referral to PHC. [Table: see text]

Cell-free Circulating Tumor DNA Variant Allele Frequency Associates with Survival in Metastatic Cancer.

Physicians are expected to assess prognosis both for patient counseling and for determining suitability for clinical trials. Increasingly, cell-free circulating tumor DNA (cfDNA) sequencing is being performed for clinical decision making. We sought to determine whether variant allele frequency (VAF) in cfDNA is associated with prognosis. We performed a retrospective analysis of 298 patients with metastatic disease who underwent clinical comprehensive cfDNA analysis and assessed association between VAF and overall survival. cfDNA mutations were detected in 240 patients (80.5%). Median overall survival (OS) was 11.5 months. cfDNA mutation detection and number of nonsynonymous mutations (NSM) significantly differed between tumor types, being lowest in appendiceal cancer and highest in colon cancer. Having more than one NSM detected was associated with significantly worse OS (HR = 2.3; P < 0.0001). VAF was classified by quartiles, Q1 lowest, Q4 highest VAF. Higher VAF levels were associated with a significantly worse overall survival (VAF Q3 HR 2.3, P = 0.0069; VAF Q4 HR = 3.8, P < 0.0001) on univariate analysis. On multivariate analysis, VAF Q4, male sex, albumin level <3.5 g/dL, number of nonvisceral metastatic sites >0 and number of prior therapies >4 were independent predictors of worse OS. Higher levels of cfDNA VAF and a higher number of NSMs were associated with worse OS in patients with metastatic disease. Further study is needed to determine optimal VAF thresholds for clinical decision making and the utility of cfDNA VAF as a prognostic marker in different tumor types.

Prostate radiotherapy for metastatic hormone sensitive prostate cancer—myth or reality?

Previously, local radiotherapy (RT) was only limited to palliate local symptoms, including bleeding or obstructive symptoms in metastatic prostate cancer patients. However, a population-based database and retrospective studies suggested that the local treatment of the prostate could improve survival in metastatic hormone-naive prostate cancer with a small metastatic burden, ‘oligometastatic’ state (1-3). Recently two randomized trials demonstrated the efficacy of local RT to prostate in metastatic prostate cancer patients (4,5).

Patient-Reported Outcome Labeling for Malignant Hematology Drugs Approved in the United States: 2011-2017

Introduction: Patient-reported outcomes (PROs), defined as any report on the status of a patient's health condition that comes directly from the patient without interpretation by anyone else, play an increasingly important role in drug development. In 2009 the FDA issued final guidance on using PRO measures to support labeling claims, to incorporate the patient perspective into the drug approval process. The 21st Century Cures Act emphasizes PROs as a differentiating element in the FDA approval process of new drugs, beyond traditional clinical outcome measures. Further, recent data has shown that intervention based on PROs can improve survival in metastatic cancers (Basch et al; 2017). The incorporation of PROs into the labeling of new drugs for malignant hematology disorders has not been studied and is the subject of this investigation.Methods: We reviewed the FDA's Novel New Drug Summaries (2011-2017) to identify drugs approved for malignant hematology indications. Drug approval packages and product labeling were accessed via the Drugs@FDA database and analyzed for PRO endpoints, measures, and labeling claims. Clinical trial designs and published study results were retrieved via the ClinicalTrials.gov website and PubMed.Results: Of 250 novel drugs approved by the FDA between 2011 and 2017, 22 (8.8%) were approved for malignant hematology indications. Interestingly, only 1 had PRO-based claims in their labeling, even though 13 of the 22 drugs (59%) collected PRO data in pivotal trials that led to their approval. Notably, the proportion of malignant hematology trials assessing PROs has increased over time, with 4 of the 5 drugs approved in 2017 for malignant hematology indications evaluating PROs in their development programs, compared with 9 of the 17 drugs approved in the preceding 6 years (80% vs. 53%). PROs evaluated included generic instruments such as the EQ-5D, and disease-specific instruments such as the EORTC QLQ-C30 (see table). Reasons cited for rejection of PRO data inclusion in drug labeling were single arm trial design, excessive missing data, statistical issues, and use of an inappropriate PRO instrument.Conclusions: While the FDA encourages PRO data submission as part of the new drug approval process, and although more than half of all malignant hematology drugs approved in the past 7 years assessed PROs during development, only 1 was able to successfully acquire labeling claims. Whether this is due to lack of PRO expertise on clinical development teams or absence of strong regulatory guidance on how best to implement PROs remains unknown and requires further research. Designing strategies to develop, validate and report PROs effectively is needed to meet regulatory requirements and enhance patients' voices in their own care. [Display omitted] DisclosuresNabhan:Cardinal Health: Employment, Equity Ownership.

Correlation of PBMC CD62Llow CD4+ T cells with irILD after nivolumab therapy.

e21018Background: Antibody blockade of programmed death (PD)-1 has led to significant prolongation of overall survival in metastatic cancers, including non-small cell lung cancer (NSCLC). However, ...

Cell-free circulating tumor DNA somatic alteration burden and its impact on survival in metastatic cancer.

12022Background: Prognostication has been a challenging subject in patients with metastatic disease. Physicians are expected to assess prognosis of patients with advanced disease both for determini...

Characterization of Tumor Cells Using a Medical Wire for Capturing Circulating Tumor Cells: A 3D Approach Based on Immunofluorescence and DNA FISH.

Circulating tumor cells (CTCs) are associated with poor survival in metastatic cancer. Their identification, phenotyping, and genotyping could lead to a better understanding of tumor heterogeneity and thus facilitate the selection of patients for personalized treatment. However, this is hampered because of the rarity of CTCs. We present an innovative approach for sampling a high volume of the patient blood and obtaining information about presence, phenotype, and gene translocation of CTCs. The method combines immunofluorescence staining and DNA fluorescent-in-situ-hybridization (DNA FISH) and is based on a functionalized medical wire. This wire is an innovative device that permits the in vivo isolation of CTCs from a large volume of peripheral blood. The blood volume screened by a 30-min administration of the wire is approximately 1.5-3 L. To demonstrate the feasibility of this approach, epithelial cell adhesion molecule (EpCAM) expression and the chromosomal translocation of the ALK gene were determined in non-small-cell lung cancer (NSCLC) cell lines captured by the functionalized wire and stained with an immuno-DNA FISH approach. Our main challenge was to perform the assay on a 3D structure, the functionalized wire, and to determine immuno-phenotype and FISH signals on this support using a conventional fluorescence microscope. The results obtained indicate that catching CTCs and analyzing their phenotype and chromosomal rearrangement could potentially represent a new companion diagnostic approach and provide an innovative strategy for improving personalized cancer treatments.

Characterization of Tumor Cells Using a Medical Wire for Capturing Circulating Tumor Cells: A 3D Approach Based on Immunofluorescence and DNA FISH

Circulating tumor cells (CTCs) are associated with poor survival in metastatic cancer. Their identification, phenotyping, and genotyping could lead to a better understanding of tumor heterogeneity and thus facilitate the selection of patients for personalized treatment. However, this is hampered because of the rarity of CTCs. We present an innovative approach for sampling a high volume of the patient blood and obtaining information about presence, phenotype, and gene translocation of CTCs. The method combines immunofluorescence staining and DNA fluorescent-in-situ-hybridization (DNA FISH) and is based on a functionalized medical wire. This wire is an innovative device that permits the in vivo isolation of CTCs from a large volume of peripheral blood. The blood volume screened by a 30-min administration of the wire is approximately 1.5-3 L. To demonstrate the feasibility of this approach, epithelial cell adhesion molecule (EpCAM) expression and the chromosomal translocation of the ALK gene were determined in non-small-cell lung cancer (NSCLC) cell lines captured by the functionalized wire and stained with an immuno-DNA FISH approach. Our main challenge was to perform the assay on a 3D structure, the functionalized wire, and to determine immuno-phenotype and FISH signals on this support using a conventional fluorescence microscope. The results obtained indicate that catching CTCs and analyzing their phenotype and chromosomal rearrangement could potentially represent a new companion diagnostic approach and provide an innovative strategy for improving personalized cancer treatments.

PROs improve survival in metastatic cancer

PROs improve survival in metastatic cancer

CD4+ T cells in PBMC to predict the outcome of anti-PD-1 therapy.

11525 Background: Antibody blockade of programmed death 1 (PD-1), has led to durable responses and significant prolongation of overall survival in metastatic cancers including non-small cell lung cancer (NSCLC). However, in clinical trials, response rates were as low as 20 %, and approximately 50 % of the patients did not achieve benefits to prolong progression free survival. These results bring us a hypothesis that there are subgroups with distinct pre-existing anti-tumor immunity resulting in different responses to anti-PD-1 therapy. We reported that effector T cells, which are capable of mediating antitumor reactivity, are primed in LNs draining growing tumors and that these T cells exclusively belong to the T cells that down-regulated CD62L (CD62Llow) subpopulation. In the absence of purified tumor antigenic proteins or peptides on many tumors, the expression of the homing molecule CD62L on T cells may serve as a surrogate marker for identifying tumor-specific immune cells. Methods: We analyzed the peripheral blood mononuclear cells (PBMC) of 50 consecutive NSCLC patients who were planned to be treated with anti-PD-1 Ab, Nivolumab after obtaining written informed consent. The patients received Nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks. Tumor response was assessed with the use of the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, at week 8 and every 8 weeks thereafter. Results: The NSCLC patients who achieved partial response (PR) or stable disease (SD) had significantly (p = 4.1x10-7) more CD62Llow CD4+ T cells in PBMC than progressive disease (PD) patients. The percentages of CD62Llow in CD4+ T cells provided sensitivity 92.9 %, and specificity 96.7 % to predict the patients who had PD. Moreover, SD patients had significantly (p = 0.0067) less regulatory T cell subpopulation than PR patients, thus, it was possible to predict PR from SD. Conclusions: These results show that the major differences in pre-existing immunity among PR, SD, and PD patients to anti-PD-1 Ab existed in CD4+ T cell balance between primed effector and regulatory T cells. Further characterization of CD62Llow CD4+ T cells including mRNA microarray, checkpoint molecules, and chemokine receptors is going on.

Gastrectomy Fails to Improve Survival in Metastatic Gastric Cancer

Whether upfront gastrectomy should be used in conjunction with chemotherapy for metastatic gastric cancer is controversial. To resolve the issue,

Phase I trial of active specific immunotherapy with autologous dendritic cells pulsed with autologous irradiated tumor stem cells in hepatitis B‐positive patients with hepatocellular carcinoma

Background and ObjectivesHepatocellular carcinoma (HCC) is often associated with chronic hepatitis due to hepatitis‐B or ‐C viruses. Active specific immunotherapy (ASI) with autologous dendritic cells (DC) presenting antigens from autologous tumor stem cell (TC) lines is associated with promising long‐term survival in metastatic cancer, but hepatitis patients were excluded. ASI might benefit high‐risk primary HCC patients following surgical resection, but first it is important to show that ASI does not exacerbate hepatitis.MethodsPreviously untreated HCC patients with a solitary lesion > 5 cm, or three lesions with at least one > 3 cm, or more than three lesions, underwent surgical resection from which autologous TC lines were established. Irradiated TC were incubated with autologous DC to create DC‐TC. After one course of trans‐arterial chemoembolization therapy (TACE), three weekly subcutaneous injections of DC‐TC suspended in granulocyte‐macrophage colony stimulating factor were administered. Patients were monitored for eight weeks.ResultsHCC cell lines were established within five weeks for 15/15 patients. Eight patients, all with chronic hepatitis B, were treated. There was no increase in hepatic transaminases, hepatitis B antigens, or viral DNA.ConclusionAutologous DC‐TC did not exacerbate HBV in these HCC patients. A phase II efficacy trial is being planned. J. Surg. Oncol. 2015 111:862–867. © 2014 Wiley Periodicals, Inc.

Passage of Humanized Monoclonal Antibodies Across the Blood- Brain Barrier: Relevance in the Treatment of Cancer Brain Metastases?

Therapeutic monoclonal antibodies have widely contributed to improving survival in metastatic cancers. However, patients are at increased risk of developing central nervous system metastases, and the survival of patients with brain metastases remains poor, challenging daily practice in medical oncology. The mechanisms limiting the use of therapeutic monoclonal antibodies for the treatment of brain tumours are their inadequate transport from blood to brain, and a probable efflux from brain to blood by way of endothelial cell transporters like the FcRn receptor. In this review, we set out to discuss published data on experimental studies on the transport across the blood-brain-barrier of monoclonal antibodies in one or other direction. We will summarize what has been achieved with commercialized antibodies, and discuss future developments for the treatment of brain metastases in cancer patients using humanized monoclonal antibodies.