End-stage Cancer Patients Research Articles

Aggressive care at the end of life: A study of practice based factors in patients with stage IV cancer.

80 Background: Numerous studies established that early utilization of palliative care-hospice services are beneficial to cancer patients. To reduce the incidence of aggressive care in terminal cancer patients, we conducted a quality improvement study to identify pertinent risk factors and develop interventions. Methods: Through chart review, we retrospectively identified patients with stage IV cancer that were followed by oncology clinic and were admitted to the University Hospital between 8/1/2015-10/31/15. For those patients who died during the last hospitalization or were discharged to hospice care, we obtained demographic, cancer related and practice related variables listed in Table. We used Mann Whitney U test and multivariable regression to find effects of factors related to length of stay (LOS) and cost of stay (COS). Results: Length of stay was significantly prolonged in those receiving chemotherapy within the past month (6 vs 3 p=0.035). Multivariate analyses found that patients with goals of care documented in the clinic had lower COS by 36.7% and LOS by 46.7%. On average, an ICU stay resulted in COS 2.2 times higher. No significant difference was seen in LOS based on a documented palliative care clinic visit or presence of an advanced directive. Conclusions: We identified practice based factors that need improvement including earlier goals of care conversations and less chemotherapy at the end of life. Identifying end stage patients in earlier admissions, collaborating with palliative care, and adding goals of care documentation to clinic note templates, are all interventions we are studying to improve care for end stage cancer patients. [Table: see text]

Using the Surprise Question To Identify Those with Unmet Palliative Care Needs in Emergency and Inpatient Settings: What Do Clinicians Think?

The surprise question (SQ), "Would you be surprised if this patient died within the next year?" is effective in identifying end-stage renal disease and cancer patients at high risk of death and therefore potentially unmet palliative care needs. Following implementation of the SQ in our acute care setting, we sought to explore hospital-based providers' perceptions of the tool. To evaluate (1) providers' perceptions regarding the feasibility of SQ use in emergency and inpatient settings, (2) clinician perceptions regarding the utility of the SQ, and (3) barriers to SQ use. A cross-sectional survey of medical providers following addition of the SQ to the electronic record for all patients admitted to a tertiary care hospital. A total of 111/203 (55%) providers participated: 48/57 (84%) emergency physicians (EPs) and 63/146 (43%) inpatient providers (IPs). Most reported no difficulty using the SQ. Modest numbers in both groups reported that the SQ influenced care delivery (EPs 37%, IPs 42%) as well as goals of care (EPs 45%, IPs 52%). At least some advance care planning discussions were prompted by the SQ (EPs 45%, IPs 58%). Team discussions were influenced by SQ use for more than half of each group. Most respondents (55%) expressed some concern that their SQ responses could be inaccurate. In this setting, clinicians indicated that use of the SQ is feasible, acceptable, and useful in facilitating advance care planning discussions among teams, patients, and families. Many reported that SQ use influenced goals of care, but concern regarding accuracy was a barrier. Additional research examining SQ accuracy and predictive ability is warranted.

Clinical decision making in the recognition of dying: a qualitative interview study

BackgroundRecognising dying is an essential clinical skill for general and palliative care professionals alike. Despite the high importance, both identification and good clinical care of the dying patient remains extremely difficult and often controversial in clinical practice. This study aimed to answer the question: “What factors influence medical and nursing staff when recognising dying in end-stage cancer and heart failure patients?”MethodsThis study used a descriptive approach to decision-making theory. Participants were purposively sampled for profession (doctor or nurse), specialty (cardiology or oncology) and grade (senior vs junior). Recruitment continued until data saturation was reached. Semi-structured interviews were conducted with NHS medical and nursing staff in an NHS Trust which contained cancer and cardiology tertiary referral centres. An interview schedule was designed, based on decision-making literature. Interviews were audio-recorded and transcribed and analysed using thematic framework. Data were managed with Atlas.ti.ResultsSaturation was achieved with 19 participants (7 seniors; 8 intermediate level staff; 4 juniors). There were 11 oncologists (6 doctors, 5 nurses) and 8 cardiologists (3 doctors, 5 nurses). Six themes were generated: information used; decision processes; modifying factors; implementation; reflecting on decisions and related decisions. The decision process described was time-dependent, ongoing and iterative, and relies heavily on intuition.ConclusionsThis study supports the need to recognise the strengths and weaknesses of expertise and intuition as part of the decision process, and of placing the recognition of dying in a time-dependent context. Clinicians should also be prepared to accept and convey the uncertainty surrounding these decisions, both in practice and in communication with patients and carers.

ED02.05 Palliative Care in Iran

It is well known that palliative care is a necessity in cancer patients, as early on as the time of diagnosis. In adult oncology, there is evidence to suggest early specialist palliative care improves HRQOL, mood, treatment decision-making, health-care utilization, advanced care planning, patient satisfaction, and end-of-life care.1 Early admission to community-based palliative care also reduces the use of Emergency departments by cancer patients in the 90 days before death.2 Palliative care for cancer patients is rather new in Iran and has a history of less than 7 years. Here we give an overview on the status of palliative care in Iran. We also present the demographics of our patients in the first and largest palliative care ward in Iran over the last two years. Iran has a population of around 80 million people. In Iran, cancer is known as the third cause of death. Adult morbidity rate of cancer in different regions of Iran is estimated 48-112 cases per million people among the females and 51-144 cases per million people among the males.3 Also, mortality rate related to cancer was about 53500 people in 2014.4 The majority of cancer patients expire in the intensive care units (ICU), whereas bed occupancy of ICUs is in crises, being about 100% in Iran. For each ICU bed, 4 people are applicants.5 We currently have around 8 active palliative care units for cancer patients and one palliative care ward in Iran, all run by charities. In these palliative care units, we have oncologists, palliative care specialists, pain specialists, psychologists, spiritual care specialists, social workers and dieticians. A total number of 3677 patients, ages between 16 and 94 (Median 61), of whom 3277 (89%) with a similar age distribution had a cancer diagnosis were referred to our palliative care unit in Firoozgar Hospital, which is run by the Ala Charity, in Tehran in the last three years. 1770 female (54%) and 1457 male (46%) advanced cancer patients were referred. A number of 388 (12%) patients had breast cancer, 339 (10%) had hematologic malignancies, 312 (10%) had esophageal or gastric cancer, 311 (10%) had colorectal cancer, 105 (3%) had a cancer of the CNS, 101 (3%) had lymphoma, 93 (3%) had renal cancer, 87 patients (3%) had ovarian cancer, 81 (2%) had lung cancer, 54 patients (2%) had prostate cancer and 50 (2%) had pancreatic cancer. The other 40% of the cancer patients had either less frequent cancers or their exact cancer site was not recorded. In most countries, the gap between death and specific therapies is considered as an indicator of the quality of physician services and more length of time will be a better indicator for physician services, while cancer patients in health system of Iran receive specific treatment and chemotherapy even to moment of death. To consider countless benefits of home care and the patients’ desire to receive services at home, if we can provide the conditions that at least 20% of end stage cancer patients receive home based palliative care, 1000 deaths will occur at home yearly, and 1000 ICU beds will be released for use for other patients with better prognosis for survival.5 For this reason, the Ala charity has also started free of charge home care services in Isfahan and Tehran. Iran, like many other countries, needs many more palliative care units as well as an expansion of home based palliative care services to advanced and very advanced cancer patients. As palliative medicine is not financially lucrative, charities play a major role in setting up, maintaining and expanding these units. 1. Salins N, Ramanjulu R, Patra L, Deodhar J, Muckaden MA. Integration of Early Specialist Palliative Care in Cancer Care and Patient Related Outcomes: A Critical Review of Evidence. Indian J Palliat Care. (2016) 22:252-7 2. McNamara BA, Rosenwax LK, Murray K, Currow DC. Early admission to community-based palliative care reduces use of emergency departments in the ninety days before death. J Palliat Med. (2013);16:774-9 3. Mousavi SM, Gouya MM, Ramazani R, et al. Cancer incidence and mortality in Iran. Annals of Oncology. (2009);20:556-63. 4. World Health Organization. Cancer country profiles in Iran 2014. Geneva: WHO; 2014. [cited 29 August 2015]. Avilable from: http://www.who.int/cancer/country-profiles/en/ 5. Heydari H. Home-based Palliative Care: A Strategy for Keeping Intensive Care Unit Beds Vacant. Int J Community Based Nurs Midwifery. (2016);4:186-7. Palliative medicine, cancer, Iran

The Relationship between Dignity Status and Quality of Life in Iranian Terminally Ill Patients with Cancer.

Background:Palliative care is an approach that has been used to care for terminally ill patients. The current study was performed to assess the association between the status of patient dignity and quality of life (QOL) in Iranian terminally ill patients with cancer.Materials and Methods:This descriptive correlational study was conducted on 210 end-stage cancer patients (102 men and 108 women) who were referred to Seyed Al-Shohada Hospital, Isfahan, Iran, in 2015. To assess dignity status, we used the Patient Dignity Inventory. The Persian version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire was used for QOL assessment.Results:There was a significant negative association between total dignity status and QOL scales. In addition, significant negative relationship was observed between dignity-related domains (loss of worth sense: r = −0.50, P < 0.001; anxiety and uncertainty: r = −0.51, P < 0.001; symptom distress: r = −0.62, P < 0.001; and loss of autonomy: r = −0.61, P < 0.001) and functional scale and some subscales of the QOL scale. In contrast, a significant positive relationship was found between dignity-related domains, and total symptom scale and fatigue. No significant relationship was observed between different items of dignity and global health status/QOL scale.Conclusions:High dignity status in terminally ill patients was associated with higher QOL in terms of functional intactness and lower symptom distress. Further studies are necessary to shed light to our findings.

Care Pathway for Cancer Survivorship in Korea: Trend of Breast Cancer Pathway from 2003 to 2010.

ObjectivesThe survival rate of cancer patients has exceeded 60%. Although cancer survivors may die of other diseases except cancer, the health management system including chronic disease prevention-management for cancer survivors, has not been established in the diverse aspects. Therefore, services according to care pathway of cancer patients need to be provided through a support system based on a platform concept that can be used to meet patient needs in various ways.MethodsA sample cohort database (2002–2010) of approximately 1 million persons—2% of the whole nation (50 million)—was used to estimate cancer survivors through a principal care pathway for cancer management. The sample cohort database was built to estimate the number of breast cancer survivors in the five stage: ‘Diagnosis and treatment,’ ‘Supportive care,’ ‘Monitoring,’ ‘Progress illness,’ and ‘Hospice care’. In this way, the scale of breast cancer survivors was estimated.ResultsThere were 330 (9.8%) cases of the incidence of cancer in 2010 in the ‘Diagnosis and treatment.’ Among the cases of the incidence of cancer in the previous year, the number of one-year survivors was 328 (9.7%); these were included in the category ‘Supportive care.’ In the ‘Monitoring’ category, 2,593 (76.9%) who maintained health lives were included. A total of 84 (2.5%) survivors were checked to identify an ongoing disease; these were included in the category ‘Progress illness.’ In the category ‘Hospice care,’ 36 (1.1%) end-stage cancer patients requiring hospice care were included.ConclusionsWe established a care pathway by survival stage in order to fulfill prevention and health management services post-treatment management steps.

Treatment with methylnaltrexone is associated with increased survival in patients with advanced cancer

Methylnaltrexone (MNTX), a peripherally acting μ-opioid receptor (MOR) antagonist, is FDA-approved for treatment of opioid-induced constipation (OIC). Preclinical data suggest that MOR activation can play a role in cancer progression and can be a target for anticancer therapy. Pooled data from advanced end-stage cancer patients with OIC, despite laxatives, treated in two randomized (phase III and IV), placebo-controlled trials with MNTX were analyzed for overall survival (OS) in an unplanned post hoc analysis. MNTX or placebo was given subcutaneously during the double-blinded phase, which was followed by the open-label phase, allowing MNTX treatment irrespective of initial randomization. In two randomized, controlled trials, 229 cancer patients were randomized to MNTX (117, 51%) or placebo (112, 49%). Distribution of patients' characteristics and major tumor types did not significantly differ between arms. Treatment with MNTX compared with placebo [76 days, 95% confidence interval (CI) 43-109 versus 56 days, 95% CI 43-69; P = 0.033] and response (laxation) to treatment compared with no response (118 days, 95% CI 59-177 versus 55 days, 95% CI 40-70; P < 0.001) had a longer median OS, despite 56 (50%) of 112 patients ultimately crossing over from placebo to MNTX. Multivariable analysis demonstrated that response to therapy [hazard ratio (HR) 0.47, 95% CI 0.29-0.76; P = 0.002) and albumin ≥3.5 (HR 0.46, 95% CI 0.30-0.69; P < 0.001) were independent prognostic factors for increased OS. Of interest, there was no difference in OS between MNTX and placebo in 134 patients with advanced illness other than cancer treated in these randomized studies (P = 0.88). This unplanned post hoc analysis of two randomized trials demonstrates that treatment with MNTX and, even more so, response to MNTX are associated with increased OS, which supports the preclinical hypothesis that MOR can play a role in cancer progression. Targeting MOR with MNTX warrants further investigation in cancer therapy. NCT00401362, NCT00672477.

88P - Treatment inferred from mutations identified using massive parallel sequencing leads to clinical benefit in some heavily pretreated cancer patients

Molecular portraits of numerous tumors have flooded oncologists with vast amounts of data. In parallel, effective inhibitors of central pathways have shown great clinical benefit. Together, this promises potential clinical benefits to otherwise end-stage cancer patients. Here, we report a clinical service offering mutation detection of archived samples using the ion Ampliseq cancer panel coupled with clinical consultation.A multidisciplinary think tank consisting of oncologists, molecular-biologists, genetic counselors, and pathologists discussed 67 heavily pretreated, advanced cancer patient cases, taking into account mutations identified using ion Ampliseq cancer panel, medical history, and relevant literature.The team generated a treatment plan, targeting specific mutations, for 41 out of 64 cases. Three patients died before results were available. For 32 patients, the treating oncologists chose not to include the panel recommendation in the treatment plan for various reasons. Nine patients were treated as recommended by the panel, 5 with clinical benefit, and 4 with disease progression.This study suggests that routine use of massive parallel tumor sequencing is feasible and can judiciously affect treatment decisions when coupled with multidisciplinary team-based decision making. Administration of personalized based therapies at an earlier stage of disease, expansion of genetic alterations examined, and increased availability of targeted therapies may lead to further improvement in the clinical outcome of metastatic cancer patients.

Oncologists' End of Life Treatment Decisions.

Optimal treatment decisions for older end-stage cancer patients are complicated, and are influenced by oncologists' attitudes and beliefs about older patients. Nevertheless, few studies have explored oncologists' perspectives on how patient age affects their treatment decisions. In-depth interviews were conducted with 17 oncologists to examine factors that influence their chemotherapy decisions for adults with incurable cancer near death. Transcripts of recorded interviews were coded and content analyzed. Oncologists identified patient age as a key factor in their chemotherapy decisions. They believed older adults were less likely to want or tolerate treatment, and felt highly motivated to treat younger patients. Qualitative analysis of in-depth interviews resulted in a nuanced understanding of how patient age influences oncologists' chemotherapy decisions. Such understanding may inform practice efforts aimed at enhancing cancer care at the end of life for older patients.

Activity of afatinib administered in a window pre-operative study in squamous cell carcinoma of the head and neck (SCCHN) : EORTC-90111.

6049Background: Targeted agents (TA) are often investigated in unselected end-stage cancer patients (pts), making difficult to fully evaluate their activity and impairing translational research. On...

Factors Affecting Physicians' Intentions to Communicate Personalized Prognostic Information to Cancer Patients at the End of Life: An Experimental Vignette Study.

To explore the effects of personalized prognostic information on physicians' intentions to communicate prognosis to cancer patients at the end of life, and to identify factors that moderate these effects. A factorial experiment was conducted in which 93 family medicine physicians were presented with a hypothetical vignette depicting an end-stage gastric cancer patient seeking prognostic information. Physicians' intentions to communicate prognosis were assessed before and after provision of personalized prognostic information, while emotional distress of the patient and ambiguity (imprecision) of the prognostic estimate were varied between subjects. General linear models were used to test the effects of personalized prognostic information, patient distress, and ambiguity on prognostic communication intentions, and potential moderating effects of 1) perceived patient distress, 2) perceived credibility of prognostic models, 3) physician numeracy (objective and subjective), and 4) physician aversion to risk and ambiguity. Provision of personalized prognostic information increased prognostic communication intentions (P < 0.001, η(2) = 0.38), although experimentally manipulated patient distress and prognostic ambiguity had no effects. Greater change in communication intentions was positively associated with higher perceived credibility of prognostic models (P = 0.007, η(2) = 0.10), higher objective numeracy (P = 0.01, η(2) = 0.09), female sex (P = 0.01, η(2) = 0.08), and lower perceived patient distress (P = 0.02, η(2) = 0.07). Intentions to communicate available personalized prognostic information were positively associated with higher perceived credibility of prognostic models (P = 0.02, η(2) = 0.09), higher subjective numeracy (P = 0.02, η(2) = 0.08), and lower ambiguity aversion (P = 0.06, η(2) = 0.04). Provision of personalized prognostic information increases physicians' prognostic communication intentions to a hypothetical end-stage cancer patient, and situational and physician characteristics moderate this effect. More research is needed to confirm these findings and elucidate the determinants of prognostic communication at the end of life.

Chemotherapy Use in the Months Before Death and Estimated Costs of Care in the Last Week of Life

ContextConsiderable attention has been paid to the disproportionately high costs of care for patients nearing death, yet little is known about the costs associated with chemotherapy use among end-stage cancer patients. ObjectivesTo compare costs of care other than chemotherapy in the last week of life based on whether cancer patients were using chemotherapy in the months just before death. MethodsA total of 311 patients with advanced cancer who died between 2002 and 2008 were studied. Data included medical records, patient baseline surveys (median four months before death), and postmortem interviews of caregivers and clinicians. Costs of care were estimated based on reports of death site and services other than chemotherapy received in the week before death (e.g., resuscitation). We tested whether end-of-life (EOL) care preferences, do-not-resuscitate order completion, or EOL discussions accounted for relationships between chemotherapy use and estimated care costs. ResultsHalf (50.5%) of patients were receiving chemotherapy at baseline. Estimated EOL care costs for patients with baseline chemotherapy use (median = $2681) were significantly higher than for patients without baseline chemotherapy use (median = $1092) (P = 0.003). This relationship persisted after adjusting for sociodemographic and clinical characteristics in a generalized linear model (mean incremental cost = $2681, 95% confidence interval $611–$4751, P = 0.01). None of the psychosocial variables accounted for the relationship between chemotherapy use and estimated care costs. ConclusionChemotherapy for end-stage cancer patients is associated with higher estimated EOL care costs. Given evidence of limited benefit and potential harm of chemotherapy for end-stage cancer patients, the cost-effectiveness of such care is questioned and further study warranted.

Pilot Evaluation of Auricular Acupressure in End-Stage Lung Cancer Patients.

Dyspnea is a common symptom in end-stage lung cancer patients and is only infrequently controlled. Currently, the use of complimentary therapies using traditional Chinese medicine (TCM), including auricular application of Vaccaria segetalis (a small seed), is understudied. Acupressure using auricular Vaccaria segetalis application has been reported as effective in reducing dyspnea when applied to a specific area of the ear associated with lung function in the TCM paradigm. The purpose of this feasibility study was to evaluate the effects of standardized auricular acupressure therapy using Vaccaria segetalis on dyspnea intensity and distress and oxygen saturation in end-stage lung cancer patients. The experimental design was three conditions with eight measurement points in time. Patients were randomly assigned to one of three treatment conditions: (1) Standard Care (SC); (2) SC with Vaccaria segetalis taped to random auricular locations (placebo); and (3) SC with Vaccaria segetalis taped to the auricular location deemed specific to lung function in TCM. Subjects were 11 hospice patients with advanced lung cancer and dyspnea. Dyspnea intensity and distress were measured by the Cancer Dyspnea Scale (CDS) and oxygen saturation was measured by pulse oximeter at eight time points. Non-parametric statistical analyses suggest the presence of acupressure effects with medium to large effects and significant effect for dyspnea effort. This pilot information suggests the need for further study of auricular acupressure using Vaccaria segetalis in the dyspneic advanced lung cancer population.

Patients with End-stage Interstitial Lung Disease may have More Problems with Dyspnea than End-stage Lung Cancer Patients.

Introduction:Patients with end-stage interstitial lung disease (ILD) do not appear to receive adequate palliative care despite apparent suffering before death. The aim of this study was to evaluate their signs, symptoms, and treatment received before death.Methods:Patients with ILD and lung cancer (LC) who were hospitalized and died in our hospital were enrolled retrospectively. Signs and symptoms and treatments at 7 days, 3 days, and 1 day before death were evaluated and compared between the two groups of patients.Results:A total of 23 patients with ILD and 59 patients with LC group were eligible for participation. Significantly more LC patients had loss of consciousness than ILD patients on 7 days (ILD: LC = 1 [5.6%]:24 [41%], P = 0.013), 3 days (1 [5.6%]:33 [56%], P < 0.001). Significantly more ILD patients had dyspnea than LC patients on 3 days (16 [89%]:38 [64%], P = 0.047) 1 day before death (21 [91%]:33 [56%], P = 0.001). On 1 day before death, significantly more LC patients received morphine than ILD patients (2 [8.7%]: 14 [24%], P = 0.015). More ILD patients received sedation (11 [48%]: 11 [19%], P = 0.007).Conclusions:End-stage ILD patients may experience dyspnea more frequently than terminal LC patients, and they need sedation. Morphine should be administered to ILD patients who have dyspnea. Additional prospective studies are needed.

Family caregivers for end-stage cancer patients are second order patients

Family caregivers for end-stage cancer patients are second order patients

Some patients with advanced malignancies also have reversible catatonia or limbic encephalitis

Two potentially treatable disorders, paraneoplastic catatonia and paraneoplastic limbic encephalitis, may be hidden within the presentation of end stage cancer patients, because catatonia and limbic encephalitis usually feature severely altered mental status, confusion, anorexia, and minimal responsiveness that are also common with people dying of cancer. If catatonia and limbic encephalitis are correctly diagnosed and treated, there should be definite and dramatic improvement that would translate into better quality of life and perhaps even resumption of cancer therapy. This editorial reviews basic features of catatonia and limbic encephalitis, and then presents a strategy to systematically screen for these in end stage cancer patients who are about to enter hospice. A protocol is outlined that could be adapted for clinical practice or for designing clinical studies.

Detection and characterization of mineralo-organic nanoparticles in human kidneys.

Ectopic calcification is associated with various human diseases, including atherosclerosis, cancer, chronic kidney disease, and diabetes mellitus. Although mineral nanoparticles have been detected in calcified blood vessels, the nature and role of these particles in the human body remain unclear. Here we show for the first time that human kidney tissues obtained from end-stage chronic kidney disease or renal cancer patients contain round, multilamellar mineral particles of 50 to 1,500 nm, whereas no particles are observed in healthy controls. The mineral particles are found mainly in the extracellular matrix surrounding the convoluted tubules, collecting ducts and loops of Henle as well as within the cytoplasm of tubule-delineating cells, and consist of polycrystalline calcium phosphate similar to the mineral found in bones and ectopic calcifications. The kidney mineral nanoparticles contain several serum proteins that inhibit ectopic calcification in body fluids, including albumin, fetuin-A, and apolipoprotein A1. Since the mineralo-organic nanoparticles are found not only within calcified deposits but also in areas devoid of microscopic calcifications, our observations indicate that the nanoparticles may represent precursors of calcification and renal stones in humans.

Abstract 4980: Rational design of combination therapies and block of acquired targeted drug resistance

Abstract Recent successes of targeted drugs on end stage cancer patients highlight the value of mutation-based biomarkers with high positive predictive value for drug response predictions. However, the impact of these drugs is often temporary, and the patients progress to acquired resistance. A common mechanism of drug evasion involves feedback mechanisms that increase expression or phosphorylation-driven activation of an alternative oncogenic pathway. The objective of this work was to set up a streamlined methodology for pre-clinical assessment of the novel drug for refractory cancer targeting, with specific focus of personalized medicine, mediated by sequencing, and seek combination therapies that would block the spontaneous drug evasion. We explored the efficacy of the combination approach on a panel of cancer patient derived xenografts in mice, using tumor size, or metabolic imaging as an end point. Each cancer case was subject to target somatic mutation screening, which resulted in a targeted drug recommendation, and then, mouse groups were treated either with sequeincing-based therapy, or with combination of these therapies with blockers of the suspected evasion mechanisms. As a blocker of the evasion mechanism and epithelial to mesenchymal transition, we characterized the utility of a molecule that leads to the destruction of IRS1/2 of the IGF1R pathway. IRS1/2 are altered during EMT and drug resistance, thus blocking them could block drug resistance, and found multiple scenarios, where the combination of this blockage with currently used targeted drugs, such as Erlotinib, Zelboraf, and Gleevec, all increase the attenuation of the cancer growth and progression. Addition of the IRS1/2 destruction to Erlotinib and Zelboraf resistant H&amp;N and melanoma cancers, respectively, lead to regression of the recurrent tumor mass. This combination therapy was further characterized by shRNA-negative screens, and kinome activity profiling, to assess further drug treatments that could be added, and in search for biomarkers that would identify patients likely to respond to the therapeutic combinations, We believe blocking the IGF1R in combination with drugs that inhibit the MAPK and tyrosine kinase receptor pathways may increase the progression free survival and expand the responding population within an array of cancer types, many of which are currently refractory to chemotherapy. Citation Format: Hadas Reuveni, Lana Kuperschmidt, Shani Carmi, Neta Moskovitz, Salomon Stemmer, Izhak Haviv. Rational design of combination therapies and block of acquired targeted drug resistance. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4980. doi:10.1158/1538-7445.AM2015-4980

The complex liaison between cachexia and tumor burden (Review).

Cachexia is a wasting syndrome that afflicts end-stage cancer patients. Whereas a consensus statement for a definition of cachexia recently has been accomplished, a useful measurement for this condition at present is lacking. The aim of the present review is to discuss the advantage of introducing the measurement of tumor burden for a better overall evaluation of cachexia. Our suggestion ensues from a somewhat novel perspective in the field of infectious disease research where a careful measurement of the pathogen load, between i.e. different host genotypes, leads to the definition of the concept of tolerance to the infectious insult. Indeed tolerance concurs, together the more classical resistance, in maintaining the host reproductive fitness or health state. Noticeably a similar reasoning may apply to tumor biology as well. Whereas the extent of cachexia increases with tumor burden, the relationship between these two correlates of tumor progression fluctuates in a broad range. We have selected from the literature studies in the rodent model where significant variation in the course of the wasting illness during cancer was observed and quantitatively assessed comparing experimental groups marked by different genotype, drug treatment, diet or gender. These studies may be further classified in two categories: the former where the experimental condition associated to milder cachexia is accompanied to a lesser tumor burden, the latter where the inhibition of cachexia results disentangled from the tumor burden, that is the whole number of cancer cells results unchanged or even, paradoxically, is increased. In addition we survey, even in the context of human malignancy, the significance and feasibility of plotting quantitative estimates of cachexia against the whole tumor burden. Ultimately, the principal endeavor of introducing the measurement of tumor burden, in both experimental and clinical oncology, may be to achieve a better assessment of the inter-individual variation in the host vulnerability to cancer cachexia.

Facility-Related Factors Influencing the Place of Death and Home Care Rates for End-Stage Cancer Patients.

In Japan, palliative home care is subject to increasing demand from patients. However, the number of deaths at home is still not as high as that of palliative home care users. This study aimed to clarify factors influencing the place of death and home care rates, involving end-stage cancer patients targeted for palliative care by a general home-visit nursing agency. A total of 87 patients who had used palliative home nursing care services provided by the study facility within a 6-year period after its opening were studied. The numbers of deaths at home supported by family physicians and those in hospital after readmission were 70 and 17, respectively. The numbers of deaths at home using services provided by the study facility and nurses belonging to it time-dependently increased, revealing a strong correlation between them. Furthermore, the place of death and home care rates were closely associated with the mean duration of home nursing services and home visits in collaboration with family physicians in charge. These results suggest that it may be possible to increase the rate of home care for end-stage cancer patients and meet their desires regarding the place of death through approaches to establish trust-based relationships with them and their families, such as strengthening manpower in home-visit nursing agencies and promoting collaboration between visiting nurses and family physicians in charge during home visits.