Futile Treatment Research Articles

Early detection of treatment futility in patients with metastatic colorectal cancer.

Purpose: Chemotherapy options for treating CRC have rapidly expanded in recent years, and few have predictive biomarkers. Oncologists are challenged with evidence-based selection of treatments, and response is evaluated retrospectively based on serial imaging beginning after 2–3 months. As a result, cumulative toxicities may appear in patients who will not benefit. Early recognition of non-benefit would reduce cumulative toxicities. Our objective was to determine treatment-related changes in the circulating metabolome corresponding to treatment futility.Methods: Metabolomic studies were performed on serial plasma samples from patients with CRC in a randomized controlled trial of cetuximab vs. cetuximab + brivanib (N = 188). GC-MS quantified named 94 metabolites and concentrations were evaluated at baseline, Weeks 1, 4 and 12 after treatment initiation. In a discovery cohort (N = 68), a model distinguishing changes in metabolites associated with radiographic disease progression and response was generated using OPLS-DA. A cohort of 120 patients was used for validation of the model.Results: By one week after treatment, a stable model of 21 metabolites could distinguish between progression and partial response (R2Y = 0.859; Q2Y = 0.605; P = 5e-4). In the validation cohort, patients with the biomarker had a significantly shorter OS (P < 0.0001). In a separate cohort of patients with HCC on axitinib, appearance of the biomarker also signified a shorter PFS (1.7 months vs. 9.2 months, P = 0.001).Conclusion: We have identified changes in the metabolome that appear within 1 week of starting treatment associated with treatment futility. The novel approach described is applicable to future efforts in developing a biomarker for early assessment of treatment efficacy.

Change in perception of the quality of death in the intensive care unit by healthcare workers associated with the implementation of the \u201cwell-dying law\u201d

PurposeThe importance of dying with dignity in the intensive care unit (ICU) has been emphasized. The South Korean government implemented the “well-dying law” in 2018, which enables patients to refuse futile life-sustaining treatment (LST) after being determined as terminally ill. We aimed to study whether the well-dying law is associated with a significant change in the quality of death in the ICU.MethodsThe Quality of Dying and Death (QODD) questionnaires were prospectively collected from the doctors and nurses of deceased patients of four South Korean medical ICUs after the law was passed (January 2019 to May 2020). Results were compared with those of our previous study, which used the same metric before the law was passed (June 2016 to May 2017). We compared baseline characteristics of the deceased patients, enrolled staff, QODD scores, and staff opinions about withdrawing LST from before to after the law was passed.ResultsAfter the well-dying law was passed, deceased patients (N = 252) were slightly older (68.6 vs. 66.6, p = 0.03) and fewer patients were admitted to the ICU for post-resuscitation care (10.3% vs. 20%, p = 0.003). The mean total QODD score significantly increased after the law was passed (36.9 vs. 31.3, p = 0.001). The law had a positive independent association with the increased QODD score in a multiple regression analysis.ConclusionOur study is the first to show that implementing the well-dying law is associated with quality of death in the ICU, although the quality of death in South Korea remains relatively low and should be further improved.

Limiting futile therapy as part of end-of-life care in intensive care units.

The debate about medical futility often involves intensive care units where life-support procedures are routinely applied. Futile therapy is part of end-of-life therapy. In the discussion about medical futility it is important to distinguish the effect of therapy from the benefit for the patient. The goal of treatment is not to maintain the function of an organ, body part or physiological activity, but to maintain health as a whole. Prolonging ineffective treatment violates the standard of good medical practice. In 2014, the first Polish guidelines on limiting futile therapy in patients treated in intensive care units were published. This document presents the official position of intensive care experts consulted by medical societies of other medical disciplines. Limitation of futile therapy by withdrawing from already used treatments or withholding new therapies does not mean that the role of medical personnel has ended. Intensive care turns into palliative care. The list of comorbidities showing a statistically significant correlation with medical futility has been refined. These include heart failure (NYHA III/IV), neoplastic disease and disseminated neoplastic process, and failure of two or more organs. The published survey results are devastating; 66-89% of intensive care nurses have provided futile treatment in their careers. Intensivists estimated that, on average, 20% of patients in intensive care units receive futile therapy. There is a need to disseminate standards and procedures related to end-of-life care in Polish intensive care units.

"His first word was 'cream'." The burden of treatment in pediatric atopic dermatitis-A mixed methods study.

The burden of treatment (BOT) is the workload of health care experienced by patients with chronic conditions and consequences on well-being. This study aimed to assess the BOT of atopic dermatitis (AD) on children and caregivers using mixed methods. The quantitative component of this mixed methods study involved the Treatment Burden Questionnaire. The qualitative component involved interviews with parents of children with moderate-severe AD. The questionnaire was completed by 168 parents; 32.1% had mild AD, 39.9% had moderate AD, and 28% had severe AD. The average burden score was 3.5 (out of 10). Average burden scores were low in mild AD (1.0 out of 10) and were proportionally higher in moderate (3.9 out of 10) and severe (5.8 out of 10) AD (p < 0.001). Increased frequency of therapy had increased perceived burden. In moderate-severe AD, oral therapy was rated as less burdensome than topical therapies. Semi-structured interviews were conducted with 15 parents of children with moderate-severe AD. Thematic analysis grouped experiences into health care burden, treatment burden, and financial burden. Insights from health care burden analysis included "mixed messages," "treatment futility," and "expectant resolution." Insights from treatment burden included treatment routine, schooling impact, and "topical-sparing" with systemic treatment. Factors of financial burden included topical treatments, clothing, and health care visits. Moderate-severe AD is associated with high BOT, particularly related to topical therapies, which may be reduced by systemic treatment. All physicians treating children with AD should avoid potentially damaging communication regarding mixed messages, treatment futility, and expectant resolution.

The Effects of Integrative Palliative Oncology on Hospital Time, Hospice Referrals, and Advanced Care Planning

Background: &#x0D; Integrative palliative oncology incorporates mental, physical, and familial aspects of care into standard cancer treatment. Patients in these programs have access to a doctor, nurse, psychologist, social worker, and chaplain who are all trained in palliative oncology whereas standard oncology does not have this team. Integrative programs improve well-being while reducing futile treatments. We hypothesize that emergency department (ED) visits, inpatient admissions, intensive care unit (ICU) stays, hospital deaths, hospice referrals, and advanced care planning (ACP) are affected by these programs.&#x0D; &#x0D; Methods: &#x0D; A retrospective chart review analyzed patients from Parkview Regional Medical Center. Cohort A included 100 patients from a palliative oncology program. Cohort B included 100 patients who received standard oncology care. Cohorts were matched on gender, age, cancer type, and stage. Number of ED visits, ICU admissions, and inpatient stays were analyzed. Hospice referrals, hospital deaths, and ACP documents were also compared.&#x0D; &#x0D; Results:&#x0D; A T-test showed no difference between ED visits, ICU stays, or inpatient admissions between cohorts. A chi-square analysis also showed no difference in hospice referrals or hospital deaths. However, there were significantly more ACP documents on file for cohort A (p = 0.000132). This suggests that palliative oncology programs do not strongly affect hospital time or hospice referrals but may impact advanced care planning.&#x0D; &#x0D; Conclusion:&#x0D; Since the benefits of palliative oncology programs do not seem related to hospital time or hospice care, another factor must be responsible for improving patients’ quality of life. These programs emphasize family involvement and planning thus explaining the significant increase in ACP documents. Perhaps this extra support and preparedness also improves patients’ moods and well-being.&#x0D; &#x0D; Impact:&#x0D; Future studies should involve a larger sample size and focus on psychological aspects of these programs to determine why they benefit patient health, specifically mental health, and what improvements can be made.

Factors Influencing Potentially Futile Treatments at the End of Life in a Multiethnic Asian Cardiology Setting: A Qualitative Study.

Modern medicine enables clinicians to save lives and prolong time to death, yet some treatments have little chance of conferring meaningful benefits for patients nearing the end-of-life. What clinicians perceive as driving futile treatment in the non-Western healthcare context is poorly understood. This study aimed to explore clinicians' perceptions of the factors that influence futile treatment at the end of life within a tertiary hospital cardiac care setting. We conducted semi-structured interviews with cardiologists, cardiac surgeons, and palliative care doctors from a large national cardiology center in Singapore. Interviews were transcribed verbatim and thematically analyzed. A total of 32 clinicians were interviewed. We identified factors that contributed to the provision of potentially futile treatment in these theme areas: patient- and family-related, clinician-related, and institutional and societal factors. Family roles and cultural influences were most commonly cited by participants as affecting end-of-life decisions and altering the likelihood of futile treatment. Specialty-specific alignments within cardiology and availability of healthcare resources were also important factors underpinning futile treatment. Family-related factors were a primary driver for futile treatment in a non-Western, multicultural setting. Future interventions should consider a targeted approach accounting for cultural and contextual factors to prevent and reduce futile treatment.

It Takes Time to Let Go.

Futile or nonbeneficial treatment is often a source of contention between care teams and family members of ICU patients. This narrative describes such a case at a cancer center. In the midst of the COVID-19 crisis, the psychosocial team had to act as a bridge between a patient's surrogate decision maker and the care team. In light of COVID-19 visitor restrictions, the psychosocial team, the surrogate/family, and the care team had to respectfully work towards what was best for the patient.

Investigating EEG biomarkers of clinical response to low frequency rTMS in depression

Repetitive transcranial magnetic stimulation (rTMS) is an effective intervention for major depressive disorder (MDD). Completing a full treatment course, however, is costly and time-consuming. Biomarkers of clinical outcome such as baseline resting-state brain activity measured with electroencephalography (EEG) may spare people futile treatment and conserve limited clinical resources. Additionally, investigating changes in EEG power post-treatment could provide insights into the working mechanism of rTMS. 39 MDD patients received 6 daily sessions of accelerated low-frequency (LF) rTMS over the right dorsolateral prefrontal cortex (DLPFC) for 5 days followed by a tapering course of 25 once-daily sessions. Resting-state EEG and heart rate (HR) measures were acquired immediately before and after a single rTMS session at 3 different timepoints: baseline, one week after the final accelerated session, and upon completion of the tapering course. The primary clinical outcome measure was the Beck Depression Inventory II (BDI-II). High relative baseline theta power in prefrontal areas and high baseline HR were associated with poorer clinical outcome. HR decreased acutely at the beginning of the patients’ first rTMS session but this effect was not associated with treatment outcome. The main limitations were small sample size and a lack of sham and healthy control group. Our results suggest that high relative theta power at baseline may be a marker of poorer response to right-sided LF rTMS. If validated, this easily applicable measure could inform rTMS protocol choice for the individual, thereby potentially speeding up patient recovery and saving clinical resources.

Limiting ICU admission from emergency services and wards

IntroductionDecisions not to admit a patient to intensive care units (ICU) as a way of limiting life support treatment (LLST) is a practice that can affect the operation of the emergency services and the way in which patients die. MethodsPost hoc analysis of the ADENI-UCI study. The main variable analysed was the reason for refusal of admission to the ICU as a measure of LLST. For the present post hoc analysis, the registered patients were divided into 2 groups: the patients assessed in the intensive medicine services from the emergency department and the patients assessed from the conventional hospitalization areas. Student t was used in the comparative statistics when the mean values of the patient sub-cohorts were compared. Categorical variables were compared with the χ2 tests. ResultsThe ADENI-ICU study included 2284 decisions not to admit to the ICU as a measure of LLST. Estimated poor quality of life (p = 0.0158), the presence of severe chronic disease (P = 0.0169) and futility of treatment (P = 0.0006) were percentage decisions with greater weight within the population of hospitalized patients. The percentage of disagreement between the consulting physician and the intensivist was significantly lower in patients assessed from the emergency services (P = 0.0021). ConclusionsThere are appreciable differences in the reasons for consultation, as well as in those for refusal of admission to an ICU between the consultations made from an emergency department and a conventional hospitalization facility.

QOLP-36. PATTERN OF CARE OF BRAIN TUMOR PATIENTS IN THE LAST MONTHS OF LIFE: ANALYSIS OF A COHORT OF 3045 PATIENTS IN THE LAZIO REGION IN THE LAST 10 YEARS

Abstract The final days of life of Brain Tumor patients (BT) present special challenges and often palliative care approach is underutilyzed. Several studies reported that BT patients in the last months of life receive frequent hospital readmissions and ER accesses as result of bad quality of End of Life care. Early integration of pallative care has been demonstrated to improve quality of care in advanced stage of disease and quality of death in cancer patients. With the aim to evaluate pattern of treatment and the rate of hospital readmission in the last months of life, we retrospectively analyzed a consecutive serie of BT patients discharged after a diagnosis of BT. METHODS: Data regarding hospital readmission and treatment received in the last two months of life were collected from the Lazio Region Healthcare database. Adult patients discharged with diagnosis ICD-9 191.* between 1/1/2010 until 31/12/2019, were included in this study. RESULTS: 6672 patients were identified and 3045 death before 31/12/2019 were included (median age 67 y;M1700). In the last month of life 42.6% received hospital reamission (4.6% intensive care unit) and 37.9% had ER accesses. 24.5% received chemotherapy and 12.1% radiotherapy. In the last 30 days 33% were readmitted in hospital and 24.2% were admitted in ER. 11.7% were treated with chemotherapy and 6% with radiotherapy. CONCLUSION: Strategies to improve quality of care at the end of life and to decrease rehospitalization and futile treatments are becoming increasingly important to improve quality of death and to reduce costs of Healthcare System.

Health literacy in communication, decision-making and outcomes among cancer patients, their families and clinicians in India: A multicentre cross-sectional qualitative study.

Cancer patients in India prefer full information regarding diagnosis and prognosis, but evidence suggests poor insight. This study aimed to identify the role of health literacy among adult patients living with cancer, their families and health professionals in decision-making and treatment outcomes in India. This cross-sectional in-depth study recruited patients, families and clinicians from three centers. Inductive thematic analysis informed a novel conceptual model. We recruited n=34 cancer patients, n=33 family members, n=11 doctors and n=14 nurses (N=92). Principle emergent themes were the following: (1) Preferences and dynamics of diagnosis and prognosis disclosure, for example, the dominant preference was for families who held hope for cure to discourage disclosure; clinicians sometimes disclosed in line with perceived ability to pay for treatment. (2) Understanding of disease and its treatment options (etiology, potential trajectory, treatment options), for example, lay understandings of cancer etiology as contamination from outside the home, and reluctance of patients to ask questions of clinicians. (3) Priorities in decision-making, for example, not engaging patients due to fear of patient distress, patients initiated on anticancer treatments without knowledge or consent, pursuing futile treatments. (4) Anxieties over finances and outcomes (disclosure, decision-making, care pathways), for example, clinicians attempting to reduce families pursuing expensive and inappropriate treatment options with patients who have poor insight, catastrophic spending based on poor decisions. The novel evidence-based health literacy model offers potential for feasible and acceptable intervention to support families in communication, disclosure and decision-making. This may improve patients' access to informed, appropriate care pathways.

Identifying Patients without a Survival Benefit following Transfemoral and Transapical Transcatheter Aortic Valve Replacement.

Transcatheter aortic valve replacement (TAVR) offers a novel treatment option for patients with severe symptomatic aortic valve stenosis, particularly for patients who are unsuitable candidates for surgical intervention. However, high therapeutical costs, socio-economic considerations, and numerous comorbidities make it necessary to target and allocate available resources efficiently. In the present study, we aimed to identify risk factors associated with futile treatment following transfemoral (TF) and transapical (TA) TAVR. Five hundred and thirty-two consecutive patients (82 ± 9 years, female 63%) who underwent TAVR between June 2009 and December 2016 at the Vienna Heart Center Hietzing were retrospectively analyzed to identify predictors of futility, defined as all-cause mortality at one year following the procedure for the overall patient cohort, as well as the TF and TA cohort. Out of 532 patients, 91 (17%) did not survive the first year after TAVR. A multivariate logistic model identified cerebrovascular disease, home oxygen dependency, wheelchair dependency, periinterventional myocardial infarction, and postinterventional renal replacement therapy as the factors independently associated with an increased one-year mortality. Our findings underscore the significance of a precise preinterventional evaluation, as well as illustrating the subtle differences in baseline characteristics in the TF and TA cohort and their impact on one-year mortality.

Prognostic role of serum neutrophil gelatinase-associated lipocalin in cardiac arrest patients: A prospective observational study.

Accurate neurological prognostication is of the utmost importance to avoid futile treatments in patients treated with targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA). This study aimed to investigate the prognostic value of serum neutrophil gelatinase-associated lipocalin (NGAL) by comparing with neuron-specific enolase (NSE), which is currently recommended by international guidelines in patients treated with TTM after OHCA.The study included 85 comatose adult patients with OHCA who underwent TTM between May 2018 and December 2020. Serum NGAL and NSE were measured at 24-hour intervals until 72 hours after return of spontaneous circulation (ROSC). The primary outcome was their prognostic performance for poor neurological outcome at 3 months after OHCA.Forty-nine patients (57.6%) had a poor neurological outcome; NGAL levels at all time points measured were significantly higher in these patients than in those with a good outcome (P < .01). NGAL showed lower maximal sensitivity (95% confidence interval [CI]) under a false-positive rate of 0% for the primary outcome compared with NSE (18.2% [95% CI 8.2–32.7] vs 66.7% [95% CI 50.5–80.4]). The combination of NGAL with NSE at 48 h showed the highest sensitivity (69.1% [95% CI 52.9–82.4]) and had the highest area under the curve (0.91 [95% CI 0.81–0.96]) for a poor outcome. The prognostic performance of NGAL alone was inadequate at all time points. However, NGAL combined with NSE at 24 and 28 hours after ROSC showed improved sensitivity compared to NGAL alone.NGAL should be considered a supplementary biomarker in combination with NSE for prognostication in patients with OHCA treated with TTM.

Moral distress in oncology nurses: A qualitative study.

Oncology nursing is a special field of practice containing many factors that cause moral distress. The purpose of this study was to explore the sources of moral distress in oncology nurses. This qualitative phenomenological study was conducted with 14 oncology nurses. The mean interview duration was 30min. Data were analyzed using qualitative inductive content analysis according to the methods of Corbin and Strauss. Four main themes were identified in the study. The first theme, related to the failure of quality of care, includes the failure to provide holistic care and competence problems (not feeling competent in oncology practice). The second theme includes biomedical ethical issues commonly observed in the field of oncology. The third theme includes treatment and care practices, consisting of futile treatments, lack of regulation for 'do not resuscitate' orders and decisions to limit life-prolonging treatment, limited informational authority of nurses, and problems related to educational practices on the patient. The final theme includes problems arising from the health care system and institution's management and the need for regulation to support ethical decisions. Oncology nurses face ethical problems in providing the quality and continuity of care they desire. It is difficult to manage the problems, especially in the end-of-life period. In order to reduce and eliminate these difficulties, it is recommended to make administrative, institutional, legislative, and systemic arrangements.

Therapeutic Effects of Time-Limited Treatment with Brivaracetam on Posttraumatic Epilepsy after Fluid Percussion Injury in the Rat.

Mounting evidence suggests the synaptic vesicle glycoprotein 2A (SV2A) targeted by levetiracetam may contribute to epileptogenesis. Levetiracetam has shown anti-inflammatory, antioxidant, neuroprotective, and possible antiepileptogenic effects in brain injury and seizure/epilepsy models, and a phase 2 study has signaled a possible clinical antiepileptogenic effect. Brivaracetam shows greater affinity and specificity for SV2A than levetiracetam and broader preclinical antiseizure effects. Thus, we assessed the antiepileptogenic/disease-modifying potential of brivaracetam in an etiologically realistic rat posttraumatic epilepsy model optimized for efficient drug testing. Brivaracetam delivery protocols were designed to maintain clinical moderate-to-high plasma levels in young (5-week-old) male Sprague-Dawley rats for 4 weeks. Treatment protocols were rapidly screened in 4-week experiments using small groups of animals to ensure against rigorous testing of futile treatment protocols. The antiepileptogenic effects of brivaracetam treatment initiated 30 minutes, 4 hours, and 8 hours after rostral parasagittal fluid percussion injury (rpFPI) were then compared with vehicle-treated controls in a fully powered blind and randomized 16-week validation. Seizures were evaluated by video-electrocorticography using a 5-electrode epidural montage. Endpoint measures included incidence, frequency, duration, and spread of seizures. Group sizes and recording durations were supported by published power analyses. Three months after treatment ended, rats treated with brivaracetam starting at 4 hours post-FPI (the best-performing protocol) experienced a 38% decrease in overall incidence of seizures, 59% decrease in seizure frequency, 67% decrease in time spent seizing, and a 45% decrease in the proportion of spreading seizures that was independent of duration-based seizure definition. Thus, brivaracetam shows both antiepileptogenic and disease-modifying properties after rpFPI. SIGNIFICANCE STATEMENT: The rpFPI model, which likely incorporates epileptogenic mechanisms operating after human head injury, can be used to efficiently screen investigational treatment protocols and assess antiepileptogenic/disease-modifying effects. Our studies 1) support a role for SV2A in epileptogenesis, 2) suggest that brivaracetam and other drugs targeting SV2A should be considered for human clinical trials of prevention of post-traumatic epilepsy after head injury, and 3) provide data to inform the design of treatment protocols for clinical trials.

HBcrAg Levels Are Associated With Virological Response to Treatment With Interferon in Patients With Hepatitis Delta.

Standard treatment of hepatitis delta virus (HDV) infection remains pegylated‐interferon alfa (peg‐IFNα) in most centers, which is not only associated with rather low efficacy but several adverse events. Hepatitis B core‐related antigen (HBcrAg) is linked to intrahepatic covalently closed circular DNA levels and has previously been suggested as response predictor in IFN‐based treatment of hepatitis B virus (HBV) mono‐infection. This study aimed to investigate the value of HBcrAg in the management of patients with HBV/HDV co‐infection undergoing peg‐IFNα treatment. The Hep‐Net‐International‐Delta‐Hepatitis‐Intervention Trial‐2 study included 120 patients co‐infected with HBV/HDV. Patients were treated for 96 weeks with peg‐IFNα and either tenofovir or placebo. Ninety‐nine patients with HDV‐RNA results 24 weeks after end of treatment (FU24) were included in this analysis, of whom 32 patients (32.3%) had undetectable HDV RNA at FU24. HBcrAg was measured at baseline, week 12, 24, 48, 96, and FU24. HBcrAg levels showed no significant correlation with HDV RNA but were significantly linked to treatment outcome. HBcrAg levels < 4.5 log IU/mL at baseline, week 24, and week 48 had high negative predictive value (NPV) for achieving undetectable HDV RNA at FU24 (81.8%, 87.1% and 95.0%, respectively). Similarly, HBcrAg levels at week 96 were significantly higher in patients with viral relapse until FU24 (3.0 vs. 3.63 log IU/mL; P = 0.0089). Baseline, week 24, and week 48 HBcrAg levels were also associated with the likelihood of achieving HBsAg level < 100 IU/mL at FU24 (HBcrAg < 3.0 log IU/mL: NPV 91.7%, 90.4% and 92.3%, respectively). Test statistics improved when combining HBcrAg with additional viral and clinical parameters. Conclusion: HBcrAg is linked to treatment response to peg‐IFNα in patients with HBV/HDV co‐infection and could be a promising marker to determine treatment futility.

Extracellular Vesicle-Associated miRNAs and Chemoresistance: A Systematic Review.

Simple SummaryThere is an urgent need for a non-invasive, specific biomarker to identify patients at risk of chemoresistance, which it is the ability of cancer cells to escape the effect of chemotherapy drugs. Extracellular vesicles contain an abundance of miRNAs that demonstrate expression across a range of cancers including breast cancer, renal cell carcinoma, lung cancer, multiple myeloma, and lymphoma. Interestingly, miRNAs encapsulated within extracellular vesicles (EVs) including exosomes display an association with chemoresistance. Here, we performed a systematic revision to evaluate the association between miRNAs within EVs and chemotherapy resistance. The summarized graphical abstract indicates that several exosome-derived miRNAs involved in chemotherapy resistance can be found among different types of cancers, such as colorectal, ovarian, breast, and lung cancer, and lymphoma.Cancer is a leading public health issue globally, and diagnosis is often associated with poor outcomes and reduced patient survival. One of the major contributors to the fatality resultant of cancer is the development of resistance to chemotherapy, known as chemoresistance. Furthermore, there are limitations in our ability to identify patients that will respond to therapy, versus patients that will develop relapse, and display limited or no response to treatment. This often leads to patients being subjected to multiple futile treatment cycles, and results in a reduction in their quality of life. Therefore, there is an urgent clinical need to develop tools to identify patients at risk of chemoresistance, and recent literature has suggested that small extracellular vesicles, known as exosomes, may be a vital source of information. Extracellular vesicles (EV) are membrane bound vesicles, involved in cell-cell communication, through the transfer of their cargo, which includes proteins, lipids, and miRNAs. A defined exploration strategy was performed in this systematic review in order to provide a compilation of key EV miRNAs which may be predictive of chemoresistance. We searched the PubMed, Science Direct, and Scopus databases using the following keywords: Extracellular vesicles OR exosomes OR EVs AND miRNA AND Chemotherapy OR Chemoresistance OR Cancer Recurrence from 2010 to 2020. We found 31 articles that reported key EV-associated miRNAs involved in cancer recurrence related to chemoresistance. Interestingly, multiple studies of the same tumor type identified different microRNAs, and few studies identified the same ones. Specifically, miR-21, miR-222, and miR-155 displayed roles in response to chemotherapy, and were found to be common in colorectal cancer, ovarian cancer, breast cancer, and diffuse large B cell lymphoma patients (DLBCL). miR-21 and miR-222 were found to favour the development of chemoresistance, whereas miR-155 exhibited a contrasting role, depending on the type of primary tumor. Whilst high levels of miR-155 were found to correlate with chemotherapy resistance in DLBCL, it was found to be predictive of an effective response towards chemotherapy in breast cancer. Thus, further research regarding the roles of these miRNAs would be beneficial in terms of designing novel tools to counteract the progression of cancer in a not-to-distant future.

P14.56 Pattern of care of Brain Tumor patients in the last months of life: analysis of a cohort of 3045 patients in the Lazio region in the last 10 years

Abstract BACKGROUND The final days of life of Brain Tumor patients (BT) present special challenges and often palliative care approach is underutilyzed. Several studies reported that BT patients in the last months of life receive frequent hospital readmissions and ER accesses as result of bad quality of End of Life care. Early integration of pallative care has been demonstrated to improve quality of care in advanced stage of disease and quality of death in cancer patients. With the aim to evaluate pattern of treatment and the rate of hospital readmission in the last months of life, we retrospectively analyzed a consecutive serie of BT patients discharged after a diagnosis of BT. MATERIAL AND METHODS Data regarding hospital readmission and treatment received in the last two months of life were collected from the Lazio Region Healthcare database. Adult patients discharged with diagnosis ICD-9 191.* between 1/1/2010 until 31/12/2019, were included in this study. RESULTS 6672 patients were identified and 3045 who have died before 31/12/2019 were included (median age 67 y;M1700). In the last two month of life 42.6% received hospital reamission (4.6% intensive care unit) and 37.9% had ER accesses. 24.5% received chemotherapy and 12.1% radiotherapy. In the last 30 days 33% were readmitted in hospital and 24.2% were admitted in ER. 11.7% were treated with chemotherapy and 6% with radiotherapy. CONCLUSION Strategies to improve quality of care at the end of life and to decrease re-hospitalization and futile treatments are becoming increasingly important to improve quality of death and to reduce costs of Healthcare System.

Second-line palliative chemotherapy, survival, and prognostic factors in patients with advanced pancreatic cancer

Introduction Pancreatic cancer is a highly lethal disease with a close association between incidence and mortality. First-line (FL) palliative chemotherapy prolongs survival and alleviates cancer-related symptoms. However, the survival benefit of second-line (SL) treatment is uncertain, as studies fail to consistently show prolonged survival for any given SL treatment, and in the absence of prognostic factors patients will receive a futile treatment. The aim of this study was to examine prognostic factors and survival in patients with pancreatic cancer, with special reference to SL therapy. Material and methods This retrospective study included all patients with histopathologically verified pancreatic adenocarcinoma who received palliative chemotherapy at Skåne University Hospital and died between 1 Feb 2015 and 31 Dec 2017. Results During the study period, a total of 170 patients with pancreatic cancer died after receiving palliative chemotherapy. Of these, 72 had received SL treatment after progression on FL treatment. Median overall survival (OS) from the start of SL treatment was 5.0 months (95% CI: 4.0–6.1). Median OS was 2.9 months for patients with performance status 2 at start of SL treatment compared to 5.3 months for patients with performance status 0–1 (p = .03), and 3.5 months (95% CI: 3.0–5.4) in patients with hypoalbuminemia (<36 g/L) at the start of SL therapy compared to 8.0 months (95% CI: 5.3–11.1) for patients with normal albumin levels (p = .009). Weight loss during FL therapy, a doubling of CA 19-9 after FL therapy, and length of progression-free survival during FL treatment were not associated with survival following SL therapy. Conclusion Poor performance status and hypoalbuminemia are negative prognostic factors for survival on SL palliative treatment in patients with advanced pancreatic cancer. Possible gain in survival should be carefully considered before initiating SL chemotherapy.

1442O Proactive early palliative care referral for cancer patients in the intensive care unit: Implementing a novel “triggers” checklist

Integrated palliative care (PC) is recommended for all cancer patients. It improves patient experience and communication, reduces symptom burden and futile medical interventions, and shortens length of hospital stay. Despite the mortality of 27-43% for cancer patients admitted to intensive care (ICU), early PC involvement has not been widely adopted. Previous studies have shown the potential for using specific “trigger” criteria to identify ICU patients for early PC referral. We show the benefits of using a novel trigger tool in practice at the time of admission to ICU in a specialist cancer hospital.