Futile Therapies Research Articles

Modern insights into the pathophysiology and treatment of pseudoachalasia.

Secondary achalasia or pseudoachalasia is a clinical presentation undistinguishable from achalasia in terms of symptoms, manometric, and radiographic findings, but associated with different and identifiable underlying causes. A literature review was conducted on the PubMed database restricting results to the English language. Key terms used were "achalasia-like" with 63 results, "secondary achalasia" with 69 results, and "pseudoachalasia" with 141 results. References of the retrieved papers were also manually reviewed. Etiology, diagnosis, and treatment were reviewed. Pseudoachalasia is a rare disease. Most available evidence regarding this condition is based on case reports or small retrospective series. There are different causes but all culminating in outflow obstruction. Clinical presentation and image and functional tests overlap with primary achalasia or are inaccurate, thus the identification of secondary achalasia can be delayed. Inadequate diagnosis leads to futile therapies and could worsen prognosis, especially in neoplastic disease. Routine screening is not justifiable; good clinical judgment still remains the best tool. Therapy should be aimed at etiology. Even though Heller's myotomy brings the best results in non-malignant cases, good clinical judgment still remains the best tool as well.

PSMA PET/CT in the Brazilian Unified Healthcare System reduces costs with futile salvage therapies in the management of cases of biochemical recurrence of prostate cancer.

To compare costs between treatment strategies employed prior to and after prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) via the Brazilian Unified Health Care System and their impact on the therapeutic management of biochemical recurrence of prostate cancer. The referring physicians were surveyed on their treatment intentions (strategies) at two different time points: prior to and after PSMA PET/CT. Cost comparison results are presented as median (IQR) for each of the two strategies. The shift in therapeutic management after PSMA PET/CT was also analyzed. The study sample included 59 patients (mean age: 65.9 years). The PSMA PET/CT result was considered positive in 38 patients (64.4%) and was found to have an impact on the treatment strategy in for 36 patients (61.0%). Prior to PSMA PET/CT, salvage therapy (i.e., treatment with curative intent) was the intended treatment for most patients, and that was significantly less so after the examination (76.3% vs. 45.8%; p < 0.001). Conversely, a strategy involving systemic (i.e., palliative) therapy became more common after PSMA PET/CT (23.7% vs. 54.2%; p < 0.001). The after-PSMA PET/CT strategy presented higher overall costs than did the before-PSMA PET/CT strategy, in all scenarios evaluated. In all scenarios, nearly half of this cost difference was related to the cost of the PSMA PET/CT itself, the remainder being related to the new treatment choices that stemmed from knowledge of the PSMA PET/CT findings. For patients treated within the Brazilian Unified Health Care System, PSMA PET/CT presented higher costs in comparison with conventional imaging methods. Adding PSMA PET/CT to the workflow had an impact on therapeutic management, mainly representing a shift from futile curative treatments to systemic palliative ones. The amount of funds that could potentially be saved by not providing such futile treatments would suffice to evaluate roughly two patients with PSMA PET/CT scans for each futile treatment strategy avoided.

Bayesian predictive probability design: theory and practical application in a prospective study

In an experiment-based prospective study aiming to determine the efficiency of a treatment, the time by which it becomes clear whether a therapy is effective or not is critical. This applies specifically to clinical trials and refers to the same extent to both successful and futile therapies. This study seeks to answer the question when there is enough evidence allowing the trial to be finalised. The key is to find enough statistical signals, working on the smallest possible sample, to make a judgment whether to extend, continue or terminate the study. The Bayesian predictive design allows drawing conclusions about the prognosis of a study considering the actual results. The article provides a theoretical background and presents a practical perspective, addressing the statistical properties and technical aspects of conducting a trial based on a predictive design. Additionally, the sensitivity of the design to the choice of prior distribution is discussed.

End-of-life Decision-making Differs Between a Cancer and a Dementia Patient: Influences of the Physician's Background Factors.

Appropriate decision-making is essential for end-of-life (EOL) care without futile therapies. However, these decisions might vary in cases of cancer and other advanced diseases according to physicians' experience, education, and values. This study aimed to compare the decisions in EOL care of advanced cancer and dementia and the factors that influence them in medical students, general practitioners (GPs), and physicians with special competence in palliative medicine (cPM). A questionnaire presenting patient scenarios concerning different decisions and ethical aspects of EOL care with additional questions on attitudes and background factors was delivered to 500 Finnish GPs, all Finnish physicians with cPM (n=82), and all graduating medical students (n=639) in 2015-2016. Altogether 601 responses were obtained (53%). Palliative care was chosen more often for a patient with advanced prostate cancer (83%) than for a patient with advanced dementia (41%) (both patients males, same age). A suspicion of iatrogenic bleeding in the prostate cancer patient decreased the willingness to choose palliative care, especially among the students. Patient benefit was regarded as an important background factor in decision making by all respondent groups, but physicians' legal protection was not considered as important among the physicians with cPM as it was among the other respondent groups. Finnish doctors and students were more likely to choose palliative care options for an advanced prostate cancer patient than for an advanced dementia patient. Decision-making was influenced by respondents' background factors and attitudes. Education on EOL care for different types of advanced and incurable diseases is highly needed.

Multivariable Prediction Model for Futile Recanalization Therapies in Patients With Acute Ischemic Stroke.

Background and ObjectivesVery poor outcome despite IV thrombolysis (IVT) and mechanical thrombectomy (MT) occurs in approximately 1 of 4 patients with ischemic stroke and is associated with a high logistic and economic burden. We aimed to develop and validate a multivariable prognostic model to identify futile recanalization therapies (FRTs) in patients undergoing those therapies.MethodsPatients from a prospectively collected observational registry of a single academic stroke center treated with MT and/or IVT were included. The data set was split into a training (N = 1,808, 80%) and internal validation (N = 453, 20%) cohort. We used gradient boosted decision tree machine learning models after k-nearest neighbor imputation of 32 variables available at admission to predict FRT defined as modified Rankin scale 5–6 at 3 months. We report feature importance, ability for discrimination, calibration, and decision curve analysis.ResultsA total of 2,261 patients with a median (interquartile range) age of 75 years (64–83 years), 46% female, median NIH Stroke Scale 9 (4–17), 34% IVT alone, 41% MT alone, and 25% bridging were included. Overall, 539 (24%) had FRT, more often in MT alone (34%) as compared with IVT alone (11%). Feature importance identified clinical variables (stroke severity, age, active cancer, prestroke disability), laboratory values (glucose, C-reactive protein, creatinine), imaging biomarkers (white matter hyperintensities), and onset-to-admission time as the most important predictors. The final model was discriminatory for predicting 3-month FRT (area under the curve 0.87, 95% CI 0.87–0.88) and had good calibration (Brier 0.12, 0.11–0.12). Overall performance was moderate (F1-score 0.63 ± 0.004), and decision curve analyses suggested higher mean net benefit at lower thresholds of treatment (up to 0.8).ConclusionsThis FRT prediction model can help inform shared decision making and identify the most relevant features in the emergency setting. Although it might be particularly useful in low resource healthcare settings, incorporation of further multifaceted variables is necessary to further increase the predictive performance.

Outcomes of a multidisciplinary shock team utilizing an integrated medical/surgical strategy: The Penn Medicine Shock Model

Background Cardiogenic shock (CS) is associated with poor prognosis, with mortality rates in excess of 40-50%. Multidisciplinary shock teams have been created to facilitate early diagnosis and appropriate escalation of support. However, there are varying approaches to implementation, resulting in variable outcomes. We describe our team's approach and outcomes over 18 months. Shock team Approach : The Penn Medicine Cardiogenic Shock Team (PMCST) was established in November 2019 and consists of physicians from Interventional Cardiology, Electrophysiology, Cardiac Surgery, and Intensive Care. The team is led by an Advanced Heart Failure Cardiologist and Cardiothoracic Surgeon, who activate other members of the team by phone for expedited decision-making. The multidisciplinary team evaluates referred patients for a potentially treatable insult and/or an appropriate exit strategy to avoid futile device placement. Accepted patients are then categorized for treatment/escalation of support according to three pathways: 1) acute myocardial infarction (AMI) shock, 2) hemodynamic (non-AMI) shock, 3) post-cardiotomy shock. All PMCST calls are maintained in a data registry. Results Between November 2019 and April 2021, the team received a total of 197 shock calls. Majority of the calls (93%) came from 20 local referring centers and 139 patients (70%) were accepted. Approximately half (53%) were admitted to the Cardiothoracic Intensive Care Unit. Temporary mechanical support devices were used in 84 patients (61%). Intra-aortic balloon pump (IABP) and extracorporeal membrane oxygenation (ECMO) were the most frequently used single platforms (IABP 29%, ECMO 23%), but the majority of patients (36%) received multiple devices. Escalation of mechanical support was required in 32 patients (38%). Combined Impella and ECMO was the most commonly implemented escalation platform (25%). In total, 39 patients (46%) were evaluated for advanced therapies, with 6 patients (7%) proceeding to durable VAD or transplant. Overall survival rate was 68%. Discussion The PMCST multidisciplinary approach utilizes an integrated medical/surgical team strategy with leadership by Advanced Heart Failure and Cardiothoracic Surgery. This approach prioritizes ongoing community partnership for early recognition and appropriate utilization of therapy, and represents a successful strategy towards implementation of timely, but not futile, mechanical support and advanced therapies. Cardiogenic shock (CS) is associated with poor prognosis, with mortality rates in excess of 40-50%. Multidisciplinary shock teams have been created to facilitate early diagnosis and appropriate escalation of support. However, there are varying approaches to implementation, resulting in variable outcomes. We describe our team's approach and outcomes over 18 months. : The Penn Medicine Cardiogenic Shock Team (PMCST) was established in November 2019 and consists of physicians from Interventional Cardiology, Electrophysiology, Cardiac Surgery, and Intensive Care. The team is led by an Advanced Heart Failure Cardiologist and Cardiothoracic Surgeon, who activate other members of the team by phone for expedited decision-making. The multidisciplinary team evaluates referred patients for a potentially treatable insult and/or an appropriate exit strategy to avoid futile device placement. Accepted patients are then categorized for treatment/escalation of support according to three pathways: 1) acute myocardial infarction (AMI) shock, 2) hemodynamic (non-AMI) shock, 3) post-cardiotomy shock. All PMCST calls are maintained in a data registry. Between November 2019 and April 2021, the team received a total of 197 shock calls. Majority of the calls (93%) came from 20 local referring centers and 139 patients (70%) were accepted. Approximately half (53%) were admitted to the Cardiothoracic Intensive Care Unit. Temporary mechanical support devices were used in 84 patients (61%). Intra-aortic balloon pump (IABP) and extracorporeal membrane oxygenation (ECMO) were the most frequently used single platforms (IABP 29%, ECMO 23%), but the majority of patients (36%) received multiple devices. Escalation of mechanical support was required in 32 patients (38%). Combined Impella and ECMO was the most commonly implemented escalation platform (25%). In total, 39 patients (46%) were evaluated for advanced therapies, with 6 patients (7%) proceeding to durable VAD or transplant. Overall survival rate was 68%. The PMCST multidisciplinary approach utilizes an integrated medical/surgical team strategy with leadership by Advanced Heart Failure and Cardiothoracic Surgery. This approach prioritizes ongoing community partnership for early recognition and appropriate utilization of therapy, and represents a successful strategy towards implementation of timely, but not futile, mechanical support and advanced therapies.

Abstract 1165: Complementary diagnostics for precision targeting of cellular pathways

Abstract Precision medicine aims to tailor treatment to an individual patient through understanding the molecular basis of their disease. Targeted therapies have the potential to optimize responses and minimize side effects, while also offering savings to the healthcare system through tailoring treatment and avoiding futile therapies. Regimes are usually designed through identifying DNA-level alterations in the tumour and selecting drugs tailored to that mutation. However, cancer is not a one-pathway disease: not all patients with a particular mutational profile will respond to the same treatment, and patients without a canonical pathway-activating alteration will be excluded from potentially life-saving treatment. To address this, we developed a NanoString assay that combines proteomic and transcriptomic profiling of 4 key cancer-related, actionable pathways (MAPK, PI3K, NF-κB and JAK/STAT). Using RNA-Seq data from gold standard cell lines with defined changes in each pathway we generated minimal sets of genes indicative of pathway activation, and integrated this with total and phospho protein measurements to show pathway activation levels. The combined panel was run on a series of isogenic cell lines and glioma samples with both known and unknown driving alterations. Overall, pathway activation is more variable than would be predicted based on DNA alterations alone, with alternate pathway activation emerging as a potential new target and implying that consideration of proteomic and/or transcriptomic-level information will be important for future therapeutic decision-making. Citation Format: Robert Siddaway, Liana Nobre, Monique Johnson, Scott Milos, Scott Ryall, Javal Sheth, Uri Tabori, Cynthia Hawkins. Complementary diagnostics for precision targeting of cellular pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1165.

Brain death and management of the potential donor.

One of the first attempts to define brain death (BD) dates from 1963, and since then, the diagnosis criteria of that entity have evolved. In spite of the publication of practice parameters and evidence-based guidelines, BD is still causing concern and controversies in the society. The difficulties in determining brain death and making it understood by family members not only endorse futile therapies and increase health care costs, but also hinder the organ transplantation process. This review aims to give an overview about the definition of BD, causes, physiopathology, diagnosis criteria, and management of the potential brain-dead donor. It is important to note that the BD determination criteria detailed here follow the AAN’s recommendations, but the standard practice for BD diagnosis varies from one country to another.

Implementation and impact of the first two years of a systemwide molecular tumor board at Henry Ford Health System (HFHS).

e19266 Background: HFHS implemented clinically-oriented Precision Medicine Program (PMP) in 2016. As part of the program, multidisciplinary molecular tumor board (MTB) was created to review complex molecular cases, providing guidance to treating medical oncologist in selecting targeted therapies and clinical trials. In some cases MTB recommended genetic counseling or recommended against/for additional molecular testing. MTB consists of oncologists, molecular pathologists, clinical trial staff, and genetic counselors. MTB was designed as teaching platform engaging hematology-oncology fellows into cases analysis and presentation. Here we present preliminary analysis of the impact of the MTB on the HFHS oncology practice. Methods: From 09/08/2017 to 12/31/2019 MTB reviewed 120 cases, 116 cases were used for this analysis. Data was abstracted using Syapse precision oncology platform, MTB recommendation note, electronic medical record (EMR), and molecular test results. Results: Out of 116 pts 83 (72%) were Caucasian, 25 (22%) African American, 4 (3%) Asian, 1 (1%) American Indian. Fifty-two % (n = 21) had an ECOG performance status of 1. Most common primary disease sites were lung (39%, n = 45) brain (12%, n = 15), and hematologic cancers (9%; n = 10), followed by breast (5%, n = 6), prostate (4%, n = 5), colon (3%, n = 4), and others (28%, n = 31). The most common genetic abnormalities discussed were atypical EGFR (n = 15), non-V600 BRAF (n = 10), KRAS (n = 8), BRCA2 (n = 5), NF2 (n = 4), PTEN (n = 4), CSF3R (n = 3), IDH1 (n = 3), TP53 (n = 3), and 29 less common mutations. Thirty five (30%) pts out of 116 total were recommended clinical trials, although only 3 patients (10% of recommended) were enrolled into trials. 31 pts (27%) were recommended off-label therapy, although trials were preferred. 18% of pts (n = 21) were recommended genetics referral, although only 3 have seen Geneticist, with two undergoing germline testing. One pt was discovered to have a germline RET V804M mutation which was originally detected in the cancer. Conclusions: The first two years of data demonstrate the utility of the MTB and provide a basis for ongoing analysis. Through multidisciplinary approach, MTB encourages care coordination and collaboration. MTB resulted in genetics referrals, clinical trial recommendations, and identification of targeted therapy options, including off label. In many cases, MTB recommendations prevented futile therapies and/or additional molecular testing.

Chronic lower leg pain: entrapment of common peroneal nerve or tibial nerve-German version

Young individuals with chronic exercise-induced lower leg pain (ELP) who have normal compartmental muscle pressures and normal imaging occasionally suffer from anerve entrapment syndrome. These patients have consistently undergone avariety of diagnostic tests and often futile therapies prior to arriving at the correct diagnosis. Awareness among traumatologists regarding these nerve entities is low. Alower leg discomfort that is frequently present at night but worsens during exercise combined with altered foot skin sensations suggests an entrapment of the common peroneal or tibial nerve. If conservative therapies fail, neurolysis is advised.

Has there been a change in the end-of-life decision-making over the past 16 years?

ObjectivesPhysicians’ decision-making in end-of-life (EOL) care includes many medical, ethical and juridical aspects. We studied the changes of these decisions over time and factors influencing them.MethodsA postal survey including two...

Chronic lower leg pain: entrapment of common peroneal nerve or tibial nerve.

Young individuals with chronic exercise-induced lower leg pain (ELP) who have normal compartmental muscle pressures and normal imaging occasionally suffer from anerve entrapment syndrome. These patients have consistently undergone avariety of diagnostic tests and often futile therapies prior to arriving at the correct diagnosis. Awareness among traumatologists regarding these nerve entities is low. Alower leg discomfort that is frequently present at night but worsens during exercise combined with altered foot skin sensations suggests an entrapment of the common peroneal or tibial nerve. If conservative therapies fail, neurolysis is advised.

Precision Oncology with Electronic Medical Records

Electronic medical record (EMR)-based precision oncology is a vision that is so far limited to a few pilot and basket studies, with the goal being the design of a proper treatment for cancer patients in real time, based on the panomics knowledge of the patient, and that of similar types of patients. It aims to deliver better treatment outcomes through the design of rational drug combinations, a lower number of futile therapies, reduced patient discomfort, and a healthy human society with a reduced risk of cancer. The concept of precision oncology began with a few cancer awareness programmes and preventative screenings almost a decade ago. However, the technique took an astronomical leap with the start of the Precision Medicine Initiative Cohort Program and Cancer Moonshot programme very recently. Both projects have invested heavily towards several goals, including the merging of cancer registries and EMR to find the best treatment options for a cancer patient, an idea which, if extended globally, will generate unprecedented possibilities for precision oncology. EMR serve as a broad platform merging a variety of patient information and expert advice to facilitate co-ordinated cancer care. In this article, a summary of the recent EMR-based precision oncology practices for prevention, diagnosis, prognosis, prediction, and their associated concerns and limitations is presented. Though the path of precision oncology is unchartered, the usefulness of real-time information derived from EMR or electronic health records will lead to better precision decision-based oncotherapies.

Perianal infectious dermatitis: An underdiagnosed, unremitting and stubborn condition.

Perianal infectious dermatitis (PID) represents a superficial inflammation of the perianal skin, which is of bacterial origin (classically, group A beta-hemolytic streptococci). This narrative review aims to critically review and summarize the available scientific literature regarding pediatric PID, being the first of its kind, to the best of the author’s knowledge. It also reports the first cases of Romanian children with PID. Multiple databases were subjected to systematic literature search (from 1966 to April 30, 2018) to identify studies and case reports of children with PID. As such, this review provides updated information about essential aspects of PID (epidemiology, etiology, pathogenesis, as well as clinical features, required investigations and therapeutic options) and of diagnostic pitfalls. Although a well-defined entity, PID remains largely underdiagnosed. PID may mimic other common conditions with skin manifestations (like candidiasis, pinworms, eczema, irritant dermatitis, anal fissure, hemorrhoids, Crohn’s disease, psoriasis, seborrheic dermatitis, zinc deficiency dermatosis and even sexual abuse), with consequent unnecessary, sometimes expensive and invasive investigations and futile therapies, which cause patients and families discomfort and distress. Since PID has an unremitting course, early recognition is imperative, as it allows for prompt and efficacious antibiotic therapy. However, PID represents a stubborn condition and, even if properly treated, its recurrence rate remains high. Further well-designed prospective randomized controlled trials, with adequate follow-up, are required in order to formulate the optimum personalized antibiotic therapy (oral alone or in association with topical medication), able to prevent recurrences. Awareness of this condition by healthcare professionals should improve patient outcomes.

Circulating tumour DNA is a potential biomarker for disease progression and response to targeted therapy in advanced thyroid cancer

BackgroundConventional biomarkers in thyroid cancer are not disease specific and fluctuate in advanced disease, making interpretation difficult. Circulating tumour DNA (ctDNA) has been shown to be a useful biomarker in other solid tumours. This is a multimutational study of ctDNA over multiple timepoints, designed to test the hypothesis that ctDNA is a potential biomarker in patients with advanced thyroid cancer. MethodsMutational analysis of archival tumour tissue was performed using NGS with a targeted gene panel. Custom TaqMan assays were designed for plasma ctDNA testing using digital droplet polymerase chain reaction. Concentrations of detected ctDNA were correlated with the conventional biomarker concentration and axial imaging status defined by the Response Evaluation Criteria in Solid Tumours criteria. ResultsTumour tissue from 51 patients was obtained, with the following histologies: 32 differentiated (differentiated thyroid cancer [DTC]), 15 medullary (medullary thyroid cancer [MTC]), three poorly differentiated and one anaplastic. NGS analysis detected variants in 42 (82%) of cases. Plasma was assayed for these patients in 190 samples, and ctDNA was detected in 67% of patients. Earlier detection of disease progression was noted in three patients with MTC. In two cases (PTC and ATC), where conventional biomarkers were not detectable, ctDNA was detected before disease progression. Changes in ctDNA concentration occurred earlier than conventional markers in response to disease progression in multiple patients with DTC receiving targeted therapies. ConclusionThe majority of patients with advanced thyroid cancer had detectable ctDNA. ctDNA measurement may offer superiority over conventional markers in several scenarios: earlier detection of progression in MTC; as an alternative biomarker when conventional markers are not available; more rapid assessment of the disease status in response to targeted therapies, thereby potentially allowing prompter discontinuation of futile therapies. These early results support the hypothesis that ctDNA may be a clinically useful biomarker in thyroid cancer.

Impact of Biochemical Failure After Salvage Radiation Therapy on Prostate Cancer–specific Mortality: Competition Between Age and Time to Biochemical Failure

BackgroundDisease progression following salvage radiotherapy (SRT) for prostate cancer (PC) is common, and the time to biochemical recurrence (BCR) is heterogeneous. ObjectiveTo describe the temporal distribution and clinical impact of BCR following SRT and model outcomes using patient age and time to BCR from SRT. Design, setting, and participantsA retrospective multi-institutional study included 547 consecutive men with lymph node–negative PC receiving SRT from 1985 to 2013. The median follow-up after SRT was 8.4 yr.Intervention All men received SRT with three-dimensional or intensity-modulated RT. Outcome measurements and statistical analysisBCR was defined as a rise in prostate-specific antigen (PSA) ≥0.2ng/ml above the PSA nadir followed by a sequentially equal or higher value. Additional outcomes included distant metastasis (DM), PC-specific mortality (PCSM), and overall mortality (OM). Cox proportional hazards models, a landmark analysis, and comparison of c-indices were used. Cumulative incidence curves were estimated from a Fine and Gray regression model. Results and limitationsThe estimated 10-yr cumulative incidence of BCR was 60%. Of the 274 men experiencing BCR, 149 (54%) had BCR within 18 mo of SRT. BCR ≤18 mo after SRT was associated with a higher risk of DM (hazard ratio [HR] 7.44, 95% confidence interval [CI] 4.91–11.3; p<0.001), PCSM (HR 12.3, 95% CI 5.95–25.2; p<0.001), and OM (HR 2.85, 95% CI 1.94–4.17; p<0.001). We provide a model to estimate the cumulative incidence of DM and PCSM using age and time to BCR. The retrospective nature of our analysis limits our findings. ConclusionsA strikingly large proportion of men experience early BCR following SRT and are at higher risk of DM and PCSM. Novel predictive biomarkers are needed to identify men harboring micrometastatic disease to avoid potentially futile local therapies or allow for intensification of systemic therapies. Patient summaryMany men will develop biochemical recurrence of prostate cancer after salvage radiotherapy. Men with biochemical recurrence within 18 mo of salvage radiotherapy constitute a cohort at higher risk of distant metastasis and prostate cancer–specific mortality.

Impact of next-generation sequencing (NGS) on diagnostic and therapeutic options in soft-tissue and bone sarcoma.

11001 Background: The utility of NGS in management of sarcoma pts remains undefined. Methods: We retrospectively analyzed the NGS profile of patients who were sequenced using a panel of 405 cancer-related genes in DNA and 265 genes rearranged in RNA. Diagnostic and therapeutic implications of mutations (mut) were evaluated through published literature (OncoKb.org, Pubmed). An algorithm was applied to determine germline mut. Following IRB approval, we evaluated the clinical outcomes of pts who underwent NGS at MSKCC. Results: From 2012–2016, 5635 pts worldwide with 56 histologies were tested. Median age of 52 yrs ( &lt; 1-88), 52% females and sarcoma NOS (n = 858) was most frequent. Tumors were sequenced to a mean coverage of 634X; 1165 fusions and &gt; 60,000 mut were found. Mut suspicious for germline defects were seen in 542 pts (9.6%) in known and novel genes ( BRCA, ARID1, FANC). Tumor mutational burden was 2.5/Mb (0–329) and glomus tumors and EHE had the highest and lowest mut, respectively. 16% and 7% of pts had treatment-linked alterations (TLA) known to respond to an FDA approved or study drug, respectively. 42% of pts had TLA eligible for NCI-MATCH, ASCO-TAPUR or other studies. Novel TLA include AKT, ESR1, BRCA, NTRK, PTCH1, SMARCB1 and others. Of the 107 MSKCC pts with clinical data, 60/107 (57%) had at least one TLA, of which 31 (30%) enrolled on a matched trial and 26 pts were ineligible or lacked access to trials. Partial/complete responses were seen with inhibitors to NTRK, IDH1, BRAF, PI3K/mTOR, MDM2, SMARCB1 and others. NGS changed the initial pathology diagnosis and treatments in 5% pts (e.g. LMS to liposarcoma, clear cell to melanoma). Resistance mutations averted futile therapies in 5% pts (e.g. Rb loss and palbociclib in liposarcoma). Conclusions: Our data suggests that NGS has a significant impact in aiding diagnosis and selecting matched therapies in sarcoma. Suspected germline aberrations, while intriguing, needs further validation.

Oxygen Therapy in the Elderly: When Nasal Cannula Is Not Enough

Respiratory disease impacts significantly on health economics, and the burden of disease increases with age. A significant proportion of patients will present to acute hospital services with respiratory failure that requires prompt and appropriate management. Multiple options are available to deliver supplemental oxygenation from simple nasal prongs to non-invasive ventilation. The development of high-flow humidified oxygen systems and non-invasive ventilation has had a significant positive impact on the care of patients in respiratory failure. However, it is of crucial importance that individual patients are taken into account as some interventions may not be appropriate. Acceptable outcomes should be documented, and if necessary, a ceiling of care should be agreed so that futile therapies are not implemented.

Personalized gene expression profiling-guided (MAGE) therapy in resistant sarcomas. Preliminary data.

e14028Background: Genomic-based profiling of tumors constitutes an encouraging approach that favors the selection of active regimens minimizing the possibility of futile therapies. Previous experie...

Personalized gene expression profiling-guided (MAGE) therapy in heavily treated metastatic breast cancer (MBC): A pilot study.

e22071 Background: Genomic-based profiling of tumors constitutes an encouraging approach that favors the selection of active regimens minimizing the possibility of futile therapies. Previous experi...