Chance Of Benefit Research Articles

Long-Term Randomized Controlled Trials of Diet Intervention Reports and Their Impact on Cancer: A Systematic Review.

Most randomized controlled trials (RCTs) assessing the impact of diet on cancer have been short term (<1 year), mostly evaluating breast cancer survivors. Given the many-year interval that is generally required for an intervention to have an impact on cancer risk or prognosis, as well as the fact that lifestyle strategies such as diet modification frequently fail due to lack of adherence over the long term, we focused this systematic review only on longer-term (≥1 year) intervention reports. Diet intervention reports focused on reducing cancer risk in overweight and obese individuals target caloric restriction (every day, some days, or most hours of each day). This study is a systematic review of RCTs lasting at least 1 year, testing dietary interventions with a primary or secondary endpoint of cancer or a biomarker linked to cancer. Fifty-one reports met our review criteria. Twenty of fifty-one (39%) reports are RCTs where the primary endpoint was cancer or a cancer-related biomarker, while the other reports evaluated reports where cancer or a cancer-related biomarker was a secondary endpoint. Thirteen of twenty (65%) primary reports evaluated isocaloric, and the remaining eight evaluated low-calorie diets. All but one of the primary and two secondary isocaloric diet reports evaluated the benefit of a low-fat diet (LFD), with the other three evaluating a Mediterranean diet (MedD). More LCD vs. isocaloric diet primary reports (71% vs. 38%) demonstrated cancer or cancer-related biomarker benefit; the difference in chance of benefit with secondary reports was 85% for LCD vs. 73% for isocaloric diets. Three of three MedD reports demonstrated benefit. Sixty-nine percent (20/29) of the secondary reports came from two large reports: the WHI diet modification trial (15 secondary reports) and the polyp prevention trial (5 secondary reports). Nineteen of twenty-two (86%) primary reports enrolled only women, and three enrolled both men and women. No study that met our criteria enrolled only men, comprising 1447 men in total vs. 62,054 women. Fifteen of twenty (75%) primary reports focus on healthy women or women with breast cancer. Adherence findings are discussed when provided. More long-term RCTs evaluating cancer and cancer-related biomarker endpoints are needed, especially for cancers at sites other than the breast.

“Food for Thought”: Improving Cognition in People With Schizophrenia

We have known that cognitive difficulties are related to functional outcomes in schizophrenia for many years. However, we have only paid attention to potential treatments relatively recently. This paper describes the development of cognitive remediation treatments to improve cognitive skills and their effects on functioning. It also reviews the types of cognitive remediation with some evidence on their effects. This evidence allowed the models of treatment to be clarified and led to a landmark paper by cognitive remediation experts around the world on the ingredients of cognitive remediation to have the best chance of benefit. This expert judgement on good clinical practice was justified by a large meta-analysis that supported the extra benefit of the four ingredients: an active therapist, massed practice of cognitive skills, the teaching of cognitive strategies and additional rehabilitation to transfer skills to real life. Although there is evidence of efficacy there is little implementation of cognitive remediation, so the review ends by suggesting a pathway to establish cognitive remediation into mental health services. The paper is a summary of a lecture given to the spring conference 2023 of the Korean Society of Schizophrenia Research. This review was also published in Psychiatric Investigation by agreement between the editors.

Abstract 5755: Mutation profiling of homologous recombination-related (HRR) genes in sarcoma patients

Abstract BACKGROUND: Homologous recombination deficiency (HRD) is associated with tumorigenesis. Therapy directed toward HRD has been approved in breast and ovarian cancer, however, whether there is a chance of benefit for patients with other cancers remains unknown. Herein, we investigated the mutation characteristics of homologous recombination-related (HRR) genes in Chinese patients with sarcoma to explore possible benefit opportunities for sarcoma patients. METHODS: The genetic landscape of HRR genes was assessed in 700 Chinese sarcoma patients with different subtypes including Rhabdomyosarcoma (RMS, n = 67), Liposarcoma (LPS, n = 58), Osteosarcoma (n = 34), Synovial sarcoma (n = 30), Leiomyosarcoma (n = 29), Ewing's sarcoma (EWS, n = 27), Angiosarcoma (n = 20), other rare (n = 375) and unknown subtypes (n = 60). Molecular profiles were performed by using next generation sequencing (NGS)-based Onco Panscan plus࣪ at Genetronhealth, a laboratory accredited by College of American Pathologists and Clinical Laboratory Improvement Amendments. RESULTS: Among the 700 patients, the overall mutation frequency of HRR genes was 19.0%. Correspond to specific subtypes, the mutation frequency of HRR genes were higher in Leiomyosarcoma (27.6%, 8/29), Angiosarcoma (25.0%, 5/20) and LPS (17.2%, 10/58) compared with RMS (14.9%, 10/67), Osteosarcoma (14.7%, 5/34), Synovial sarcoma (13.3%, 4/30) and EWS (3.7%, 1/27). ATRX was the most commonly mutated gene (5.1%, n = 36) and was preferentially identified in Leiomyosarcoma (10.3%) and Angiosarcoma. (10.0%), followed by ARID1A (3.1%, n = 22), ATM (2.1%, n = 15) and FANCA/C/D2/E/F/G/L (1.7%, n = 12). The median tumor mutational burden (TMB) was 2.35 in patients with HRD and 0.94 in patients without HRD. Although BRCA1 and BRCA2 mutations were less common overall (1.1% and 0.7%), a significant proportion of BRCA1 and BRCA2 mutations was found in Angiosarcoma, Liposarcoma and Leiomyosarcoma (5.0%, 3.4% and 3.4%, respectively). CONCLUSION: Our results reported the genetic landscape of HRR genes in Chinese sarcoma patients, providing a reference for the clinical application of PARP inhibitors. Citation Format: Feng Gao, Xuejiao Liu, Xiaojuan Wang, Chunyang Wang, Tonghui Ma, Changsheng Yang. Mutation profiling of homologous recombination-related (HRR) genes in sarcoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5755.

Biosimulation Using the Cellworks Computational Omics Biology Model (CBM) Identifies Immune Modulation As a Key Pathway for Predicting Azacitidine (AZA) Response in Myelodysplastic Syndromes (MDS)

Background: DNA methyltransferase inhibition (DNMTi) with the hypomethylating agents (HMA) azacitidine (AZA) or decitabine, remains the mainstay of therapy for the majority of high-risk Myelodysplastic Syndromes (MDS) patients. Nevertheless, only 40-50% of MDS patients achieve clinical improvement with DNMTi. There is a need for a predictive clinical approach that can stratify MDS patients according to their chance of benefit from current therapies and that can identify and predict responses to new treatment options. Ideally, patients predicted to be non-responders (NR) could be offered alternative strategies while being spared protracted treatment with HMA alone that has a low likelihood of efficacy. Recently, an intriguing discovery of immune modulation by HMA has emerged. In addition to the benefits of unsilencing differentiation genes and tumor suppressor genes, HMA's reactivate human endogenous retroviral (HERV) genes leading to viral mimicry and upregulation of the immune response as a major mechanism of HMA efficacy. Although the PD-L1/PD1 blockade plus HMA has been recognized as a beneficial combination, there are no established markers to guide decision-making. We report here the utility of immunomic profiling of chromosome 9 copy number status as a significant mechanism of immune evasion and HMA resistance.Methods: 119 patients with known clinical responses to AZA were selected for this study. Publicly available data largely from TCGA and PubMed was utilized for this study. The aberration and copy number variations from individual cases served as input into the Cellworks Computation Omics Biology Model (CBM), a computational biology multi-omic software model, created using artificial intelligence heuristics and literature sourced from PubMed, to generate a patient-specific protein network map. Disease-biomarkers unique to each patient were identified within protein network maps. The Cellworks Biosimulation Platform has the capacity to biosimulate disease phenotypic behavior and was used to create a disease model and then conduct biosimulations to measure the effect of AZA on a cell growth score comprised of a composite of cell proliferation, viability, apoptosis, metastasis, and other cancer hallmarks. Biosimulation of drug response was conducted to identify and predict therapeutic efficacy.Results: Although AZA treatment increased tumor associated antigens and interferon signaling, it also increased PD-L1 expression to inactivate cytotoxic CD8(+) T cells. Copy number alterations of the chromosome 9p region were found to significantly drive PD-L1 expression with multiple genes such as CD274, IFNA1, IFNA2, JAK2, PDCD1LG and KDM4C playing a role in PD-L1 regulation further increasing immune suppression (Figure 1). Among 6 cases of chromosome 9p aberration in this dataset, 9p amp (n=2) were clinical non-responders (NR) while 9p del (n=4) were responders (R) to AZA. In principle, checkpoint immunotherapy could improve outcomes for patients with 9p abnormalities. Additionally, copy number variation loss of key genes located on chromosome 16 involved in antigen processing and presentation such as CIITA, CTCF, IRF8, PSMB10, NLRC5, and SOCS1 were found to negatively impact AZA sensitivity (NR=4; R=0); these patients would also be unlikely to respond to checkpoint immunotherapy. Also, aberrations in melanoma antigen gene (MAGE) family proteins (NR=2; R=O), and STT3A (NR=1; R=5) were found to impact AZA efficacy by decreasing antigen processing on tumor cells.Conclusion: Based on the results from the Cellworks Biosimulation Platform applied to the CBM, copy number variants of chromosome 9p and 16 can be converted into CBM-derived biomarkers for response to checkpoint immunotherapy in combination with HMA. Our results support a future prospective evaluation in larger cohorts of MDS patients. [Display omitted] DisclosuresHoward: Servier: Consultancy; Cellworks Group Inc.: Consultancy; Sanofi: Consultancy, Other: Speaker fees. Kumar: Cellworks Group Inc.: Current Employment. Castro: Bugworks: Consultancy; Exact sciences Inc.: Consultancy; Guardant Health Inc.: Speakers Bureau; Cellworks Group Inc.: Current Employment; Caris Life Sciences Inc.: Consultancy; Omicure Inc: Consultancy. Grover: Cellworks Group Inc.: Current Employment. Mohapatra: Cellworks Group Inc.: Current Employment. Kapoor: Cellworks Group Inc.: Current Employment. Tyagi: Cellworks Group Inc.: Current Employment. Nair: Cellworks Group Inc.: Current Employment. Suseela: Cellworks Group Inc.: Current Employment. Pampana: Cellworks Group Inc.: Current Employment. Lala: Cellworks Group Inc.: Current Employment. Singh: Cellworks Group Inc.: Current Employment. Shyamasundar: Cellworks Group Inc.: Current Employment. Kulkarni: Cellworks Group Inc.: Current Employment. Narvekar: Cellworks Group Inc.: Current Employment. Sahni: Cellworks Group Inc.: Current Employment. Raman: Cellworks Group Inc.: Current Employment. Balakrishnan: Cellworks Group Inc.: Current Employment. Patil: Cellworks Group Inc.: Current Employment. Palaniyeppa: Cellworks Group Inc.: Current Employment. Balla: Cellworks Group Inc.: Current Employment. Patel: Cellworks Group Inc.: Current Employment. Mundkur: Cellworks Group Inc: Current Employment. Christie: Cellworks Group Inc.: Current Employment. Macpherson: Cellworks Group Inc.: Current Employment. Marcucci: Abbvie: Other: Speaker and advisory scientific board meetings; Novartis: Other: Speaker and advisory scientific board meetings; Agios: Other: Speaker and advisory scientific board meetings.

Abstract SP086: Rationale for combination therapies

Abstract There has been a lot of emerging clinical data in the treatment of early and late stage breast cancer with PD-1/PD-L1 inhibitors in the last 12 months. We have learnt several important points relevant for future development in breast cancer patients. Most important of these is the observation that early-stage disease has a different immune context to advanced disease. This is evidenced by study results that in the neoadjuvant settings PD-(L)1 inhibitors have efficacy in both PD-L1 positive and negative populations, whereas in the advanced setting, efficacy has only been reported in PD-L1 positive patients. It has been hypothesized that chemotherapy, or certain types of chemotherapy, may be more “immunogenic” than others, but thus far, there is scant evidence to support this. Rather it is more likely that the immune context is important. In the early-stage setting, many primary breast cancers (triple negative and HER2-positive) are highly infiltrated with immune cells, the cancers has received no prior treatment, and cancer burden is low, confined to the breast and ultimately completely removed. In contrast, in the advanced setting, the immune infiltrate is low to non-existent, patients often have higher disease burden, hostile tumor microenvironments in multiple organs sites, and have received prior treatment, implying that the cancer has evolved to become treatment resistant, as well as more efficient at suppressing or evading host immune detection. Hence, in the setting of recurrent disease, and likely also in the locally advanced setting, despite chemotherapy usage and objective tumor shrinkage, it is the pre-existing immunity that ultimately dictates the chances of benefit from PD-(L)1 inhibitors. What combinations are likely therefore to be effective in the advanced setting where immunity does not exist? Targeted therapies such as MEK and AKT inhibitors are being evaluated in clinical trials, thus far have proven disappointing. New antibody drug conjugates (ADCs) such as Sacituzumab Govetecan and DS-8201a have shown impressive anti-tumor activity in the advanced setting. However, given their proven cytotoxic bystander effects on nearby cells, it will be essential to evaluate ADCs and immunotherapy sequencing approaches to ensure that the scant amount of pre-existing local TIL is also not destroyed. Interestingly a recent study in advanced HER2-positive breast cancer (KATE2) reported benefit of atezolizumab to trastuzumab emantasine also in only PD-L1 positive patients. Notably T-DM1 does not have prominent bystander effects. Other possibilities to create immunity in the advanced setting include radiotherapy, more potent anti-HER2 agents, as well as genetically engineered T cell receptor or chimeric antigen receptor T cells, and agents targeting T regulatory cells. This task is likely to be a very challenging as it will require more than making “cold” tumors “hot”, as is probable that we will need to find the means that can re-invigorate the whole host immune system in the context of advanced breast cancer. Citation Format: S Loi. Rationale for combination therapies [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP086.

Academic physician specialists’ views toward the unproven stem cell intervention industry: areas of common ground and divergence

Background and AimsPremature commercialization of unproven stem cell interventions (SCIs) has received significant attention within the regenerative medicine community. Patients considering SCIs may encounter misinformation and seek out guidance from their physicians who are trusted brokers of health information. However, little is known about the perspectives of academic physician specialists toward the SCI industry. The purpose of this study was to capture the attitudes of physician specialists with experience addressing patient questions about unproven SCIs. MethodsThe authors undertook 25 semi-structured interviews with academic physicians in cardiology, ophthalmology, orthopedics, pulmonology and neurology primarily from one academic center. ResultsThe authors identified two major themes: concerns and mediators of appropriateness of offering SCIs as therapies to patients. Specialists were generally aware of the industry and reported scientific and commercial concerns, including the scientific uncertainty of SCIs, medical harms to patients, misleading marketing and its impact on patient informed consent and economic harms due to large out-of-pocket costs for patients. All specialists outside of orthopedics voiced that it was inappropriate to be offering SCIs to patients today. These views were informed by previously expressed concerns surrounding safety and properly informing patients, levels of evidence needed prior to offering SCIs therapeutically and desired qualifications for clinicians. Among the specialties, orthopedists reported that under certain conditions, SCIs may be appropriate for patients with limited clinical options but only when safety is adequate, expectations are managed and patients are well informed about the risks and chances of benefit. Most participants expressed a desire for phase 3 studies and Food and Drug Administration approval prior to marketing SCIs, but some also shared the challenges associated with upholding these thresholds of evidence, especially when caring for out-of-option patients. ConclusionsThe authors’ results suggest that medical specialists are aware of the industry and express several concerns surrounding SCIs but differ in their views on the appropriateness and clinical evidence necessary for offering SCIs currently to patients. Additional educational tools may help physicians with patient engagement and expectation management surrounding SCIs.

AR-V7 and prediction of benefit with taxane therapy: Final analysis of PROPHECY.

184 Background: We previously found that men with AR-V7 (+) poor risk mCRPC have a low chance of benefit with abiraterone or enzalutamide. The benefits of subsequent taxane chemotherapy based on AR-V7 status may help inform treatment decisions. Methods: We conducted a multicenter prospective study of men with poor risk mCRPC (PROPHECY, NCT02269982) starting Abi or Enza and subsequent taxane chemotherapy. AR-V7 status from CTCs was assessed before abi/enza and again before taxane chemotherapy using the Epic nuclear protein assay or the Johns Hopkins Adnatest assay. The primary endpoint was to test the association of AR-V7 with radiographic/ clinical progression free survival (PFS) and OS with taxane chemotherapy, using the proportional hazards model, adjusting for Cell Search enumeration and clinical risk score. Results: We enrolled 118 men with mCRPC starting Abi/Enza; of these, 51 were evaluable with CTC AR-V7 testing and received subsequent taxane chemotherapy. With 50 PFS events, see table for final results. While AR-V7 positivity was associated with worse outcomes overall, AR-V7 (+) patients had similar PFS, OS, and confirmed &gt;50% PSA declines adjusting for CTC enumeration and clinical prognostic factors. Concordance between the two AR-V7 assays pre-taxane was 0.78 (kappa 0.46). AR-V7 positivity increased at progression on abi/enza, but not following taxane chemotherapy. Conclusions: Men with AR-V7 positive mCRPC have poor outcomes, but may benefit from taxane chemotherapy after progression on abi/enza. AR-V7 may provide a helpful predictive biomarker to guide treatment with a second AR inhibitor or a taxane. Clinical trial information: NCT02269982. [Table: see text]

Predicting diabetic foot ulcer infection using the neutrophil-to-lymphocyte ratio: a prospective study.

To investigate whether the neutrophil-to-lymphocyte ratio (NLR) may be used in the early stage risk assessment and follow-up in diabetic foot infection. Over a five-year study, NLR values on admission and day 14 of treatment were matched with their laboratory and clinical data in a cohort study. Patients were followed-up or consulted in several clinics or polyclinics (infectious diseases). Admission time NLR was higher, in severe cases as indicated by both Wagner and PEDIS infection scores (severe versus mild Wagner score NLR 6.7 versus 4.2; p=0.04; for PEDIS score NLR 6.3 versus 3.6; p=0.03, respectively). In patients who underwent vascular intervention (12.6 versus 4.6; p=0.02); amputation indicated (9.2 versus 4.1; p=0.005) and healed afterwards (6.9 versus 4.3; p<0,001), when matched with others. NLR was also found to be correlated with duration of both IV antibiotic treatment (r=0.374; p=0.005) and hospitalisation (r=0.337; p=0.02). Day 14 NLR was higher in patients who underwent vascular intervention (5.1 versus 2.9; p=0.007) when matched to others. Patients with higher NLR values at admission had more severe diabetic foot infection, higher risk for amputation, need for long-term hospitalisation and aggressive treatment. However, they also have more chance of benefit from treatment.

Taking societal cost into clinical consideration: U.S. physicians’ views

Background: Recent campaigns (e.g., the American Board of Internal Medicine Foundation’s Choosing Wisely) reflect the increasing role that physicians are expected to have in stewarding health care resources. We examine whether physicians believe they should pay attention to societal costs or refuse requests for costly interventions with little chance of patient benefit. Methods: We conducted a secondary analysis of data from a 2010 national survey of 2016 U.S. physicians sampled from the AMA Physician Masterfile. Criterion measures were agreement or disagreement with two survey items related to costs of care. We also examined whether physicians’ practice and religious characteristics were associated with their responses. Results: The adjusted response rate was 62% (1156/1878). Forty-seven percent of physicians agreed that physicians “should not consider the societal cost of medical care when caring for individual patients,” whereas 69% agreed that physicians “should refuse requests from patients or their families for costly interventions that have little chance of benefitting the patient.” Physicians in specialties that care for patients at the end of life were more supportive of refusing such costly interventions. We did not find consistent associations between physicians’ religiosity and their responses to these items, though those least supportive of taking into account societal cost were disproportionately from Christian affiliations. Conclusion: Physicians were nearly evenly divided regarding whether they should help control societal costs when caring for individual patients, but a strong majority agreed that physicians should refuse costly interventions that have little chance of benefit.

Health Care Spending: Changes in the Perceptions of the Australian Public.

BackgroundIncreasing demand for services and rising health care costs create pressures within the Australian health care system and result in higher health insurance premiums and out-of-pocket costs for consumers.ObjectiveTo measure changes in consumer views on the quality of the Australian health care system, contributors to rising costs and attitudes towards managing these costs.MethodsTwo computer-assisted telephone interviews were conducted in 2006 (533 respondents) and 2015 (1318 respondents) and results compared.ResultsMore respondents in 2015 rated the Australian health care system ‘very adequate’ than in 2006 (22.3% vs 8.3%; Odds Ratio OR 3.2, 99% CI 2.1, 5.1) with fewer ‘concerned’ or ‘fairly concerned’ about the health care costs (69.0% vs 85.7%; OR 0.37, 99% CI 0.25, 0.53). The 2015 respondents were more likely to identify new treatments for cancer (77% vs 65.7%; OR 1.75, 99% CI 1.30, 2.35) and community expectations for access to the latest technologies (73.8% vs 67%; OR 1.39, 99% CI 1.04, 1.86) as contributors to rising health care costs. While more 2015 respondents agreed that patients should pay a greater part of the health care costs, this remained a minority view (37.9% vs 31.7%; OR 1.32, 99% CI 0.99, 1.76). They were less likely to agree that doctors should offer medical treatments regardless of the cost and chance of benefit (63.6% vs 82.9%; OR 0.36, 99% CI 0.25, 0.50).ConclusionsSatisfaction with the Australian health care system has increased over time. Consumers recognise the cost pressures and have lower expectations that all services should be provided regardless of their costs and potential benefit. Public consultation on the allocation of health care resources and involvement in health care decision-making remains important. There should be community consultation about the principles and values that should guide resource allocation decisions.

Evidence-based guidelines for recommending cochlear implantation for young children: Audiological criteria and optimizing age at implantation

Objective: Establish up-to-date evidence-based guidelines for recommending cochlear implantation for young children. Design: Speech perception results for early-implanted children were compared to children using traditional amplification. Equivalent pure-tone average (PTA) hearing loss for cochlear implant (CI) users was established. Language of early-implanted children was assessed over six years and compared to hearing peers. Study sample: Seventy-eight children using CIs and 62 children using traditional amplification with hearing losses ranging 25–120 dB HL PTA (speech perception study). Thirty-two children who received a CI before 2.5 years of age (language study). Results: Speech perception outcomes suggested that children with a PTA greater than 60 dB HL have a 75% chance of benefit over traditional amplification. More conservative criteria applied to the data suggested that children with PTA greater than 82 dB HL have a 95% chance of benefit. Children implanted under 2.5 years with no significant cognitive deficits made normal language progress but retained a delay approximately equal to their age at implantation. Conclusions: Hearing-impaired children under three years of age may benefit from cochlear implantation if their PTA exceeds 60 dB HL bilaterally. Implantation as young as possible should minimize any language delay resulting from an initial period of auditory deprivation.

Abstract P5-11-02: Survival benefit needed to undergo chemotherapy: Patients and physicians preferences

Abstract Background: Data regarding patients (pts) and physicians' preferences for modern adjuvant chemotherapy (CT) are limited. Prior studies suggested that most pts with early stage breast cancer were willing to receive 6 months of adjuvant cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) for modest survival benefits (e.g. most women would have accepted 3-6 months extension of life). Methods: E5103 was a phase III trial which randomized node positive or high risk node negative breast cancer pts to receive adjuvant CT (doxorubicin, cyclophosphamide and paclitaxel) with either placebo or bevacizumab. Telephone based surveys were administered to all pts enrolled on E5103 between 01/Jan/10 and 08/Jun/10, as part of a Decision-Making/Quality of Life component. Results presented here are part of the 18 months post-enrollment follow-up. Pts were asked to rate the survival benefit needed to justify 6 months of CT. A complementary survey was sent to all physicians who registered at least one pt on E5103. Results: 465 out of 519 eligible pts (90%) responded to this survey at 18 months. Main reasons for non response were: inability to reach the patient (6%) or patient refusal (2%). Median pts age was 51 (25-76); 42% of pts had at least a college degree. The majority had at least Stage II cancer. 179 (16%) physicians participated, among whom median age was 50 (35-70). The median years in practice was 17 (3-38); 78% of physicians worked on large size practices, 72% saw at least 5 new breast cancer pts/month, and 77% enroll between 1-4 pts on trials/month. We found considerable variation in pts preferences particularly for modest survival benefits: a substantial minority of pts (24%) would consider 6 months of CT definitely worthwhile for 1 month survival benefit, 18% would possibly consider it and 56% would not. The percentage considering CT definitely worthwhile increased with greater benefit, but did not reach 100%, even with 24 months survival benefit. About half of pts considered 6 months of CT definitely worthwhile for 9 months benefit, 70% for 12 months and 84% for 24 months. Physicians were less likely to accept CT for a small chance of benefit (34% of pts vs. 5% of physicians would definitely consider CT worthwhile for 2 months of benefit). For longer benefit, pts and physicians choices were similar (84% of pts vs. 92% of physicians would definitely consider CT worthwhile for 24 months benefit). Table Yes, definitely worthwhileYes, maybeNo, not worthwhileNo answerConsider 6 months of CT to live:PtsPhysiciansPtsPhysiciansPtsPhysiciansPts/Physicians*1 month longer24%3%18%15%56%80%2%2 months longer34%5%23%32%41%60%2%6 months longer44%32%35%54%19%12%2%9 months longer53%51%34%42%11%5%2%12 months longer70%75%23%22%5%1%2%24 months longer84%92%12%5%2%1%2%n Pts= 465; n Physicians= 179; * equal results in both groups Conclusions: This subgroup of pts who had undergone modern adjuvant CT in a large multicenter randomized controlled trial and these physicians who registered pts on the same trial had different cutoffs for acceptable levels of benefits and risks when considering adjuvant chemotherapy. It is important to engage pts in determining whether CT is or is not a "reasonable" option for treatment. Citation Format: Vaz Luis I, O'Neill A, Sepucha K, Miller KD, Baker E, Dang CT, Northfelt DW, Winer EP, Sledge GW, Schneider BP, Partridge A. Survival benefit needed to undergo chemotherapy: Patients and physicians preferences. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-11-02.

Does Introducing Imprecision around Probabilities for Benefit and Harm Influence the Way People Value Treatments?

Imprecision in estimates of benefits and harms around treatment choices is rarely described to patients. Variation in sampling error between treatment alternatives (e.g., treatments have similar average risks, but one treatment has a larger confidence interval) can result in patients failing to choose the option that is best for them. The aim of this study is to use a discrete choice experiment to describe how 2 methods for conveying imprecision in risk influence people's treatment decisions. We randomized a representative sample of the Canadian general population to 1 of 3 surveys that sought choices between hypothetical treatments for rheumatoid arthritis based on different levels of 7 attributes: route and frequency of administration, chance of benefit, serious and minor side effects and life expectancy, and imprecision in benefit and side-effect estimates. The surveys differed in the way imprecision was described: 1) no imprecision, 2) quantitative description based on a range with a visual graphic, and 3) qualitative description simply describing the confidence in the evidence. The analyzed data were from 2663 respondents. Results suggested that more people understood imprecision when it was described qualitatively (88%) versus quantitatively (68%). Respondents who appeared to understand imprecision descriptions placed high value on increased precision regarding the actual benefits and harms of treatment, equivalent to the value placed on the information about the probability of serious side effects. Both qualitative and quantitative methods led to small but significant increases in decision uncertainty for choosing any treatment. Limitations included some issues in defining understanding of imprecision and the use of an internet survey of panel members. These findings provide insight into how conveying imprecision information influences patient treatment choices.

Jacob Chose Hospice: A Critique of Invasive End-of-Life Care

Jacob Chose Hospice: A Critique of Invasive End-of-Life Care

Societal preferences for rheumatoid arthritis treatments: evidence from a discrete choice experiment.

There is a concern that cost-effectiveness analysis using quality-adjusted life years does not capture all valuable benefits of treatments. The objective of this study was to determine the value society places on aspects of RA treatment to inform policymaking. A discrete choice experiment was administered to a representative sample of the Canadian general population. The discrete choice experiment, developed using focus groups, had seven attributes (route and frequency of administration, chance of benefit, chance of serious and minor side effects, confidence in evidence and life expectancy). A conditional logit regression model was used to estimate the significance and relative importance of attributes in influencing preferences on the quality-adjusted life years scale. Responses from 733 respondents who provided rational responses were analysed. Six attribute levels within four attributes significantly influenced preferences for treatments: a willingness to trade a year of life expectancy over a 10-year period to increase the probability of benefiting from treatment, or two-thirds of a year to reduce minor or serious side effects to the lowest level or improve the confidence in benefit/side-effect estimates. There was also some evidence of a preference for oral drug delivery, though a subgroup analysis suggested this preference was restricted to injection-naive respondents. Our results suggest society values the degree of confidence in the estimates of risks and benefits of RA treatments and the route of administration, as well as benefits and side effects. This study provides important evidence to policymakers determining the cost-effectiveness of treatments in arthritis.

Colon cancer screening in U.S. adults aged 65 and older according to life expectancy and age.

To examine receipt of colorectal cancer (CRC) screening according to age and life expectancy (LE) in adults aged 65 and older. Population-based survey. United States. Community dwelling adults aged 65 and older who participated in the 2008 or 2010 National Health Interview Survey (N = 7,747). Receipt of CRC screening (e.g., colonoscopy within 10 years) was examined according to age and LE (≥10 and <10 years), adjusting for sociodemographic characteristics and survey year. Frequency of CRC screening was also examined according to age and LE at time of screening (e.g., age at colonoscopy rather than at interview). Participants screened when they were aged 75 and older or had less than a 10-year LE were considered to have received screening inconsistent with guidelines. Overall, 38.5% of participants had less than a 10-year LE; 40.2% were aged 75 and older, and 56.3% had received recent CRC screening (90.1% by colonoscopy). CRC screening was higher in 2010 (58.9%) than 2008 (53.7%, P <.001) and was associated with longer LE and younger age, although 51.1% of adults aged 75 and older reported receiving CRC screening, as did 50.9% of adults with less than a 10-year LE. Based on age and LE at time of screening (rather than at interview), 28.4% of CRC screening of adults aged 65 and older was targeted to those aged 75 and older and those with less than a 10-year LE. Of adults aged 65 to 75 with a 10-year LE or more (adults recommended for screening by guidelines), 39.2% had not recently been screened. Older adults with little chance of benefit because of limited LE commonly undergo CRC screening, whereas many adults aged 65 to 75 with a 10-year LE or greater are not screened.

A practical approach to risk-benefit estimation in pediatric drug research.

One of the most difficult challenges in pediatric drug research is in exposing children to risk, often without a balanced chance of benefits. While the concept of risk is similar in adult research, the adult patient can decide for himself/herself on an acceptable level of risk, whereas children have to accept the decisions of their guardians. This paper attempts to put the complexities of estimating risk in pediatric drug research into their practical perspective, and to familiarize the reader with the way such processes are conducted in different parts of the world. Although there are regional differences, all authorities typically quantify risks of pediatric research in general, and drug research in particular, in three levels: those experienced in day-to-day life; risks slightly above this 'baseline' risk; and risks substantially above 'baseline risk'. Proportionally, the diligence of the ethics process depends on these levels, as well as on the potential benefits (or lack of) to the child involved in the research. Importantly, risk is context dependent, and a particular intervention may be effective or safe in one setting but not in another, based on local experience, staffing levels, and similar variabilities.

Lyme disease: authentic imitator or wishful imitation?

Lyme disease: authentic imitator or wishful imitation?

Current management of advanced melanoma: a transformed landscape.

The prognosis for patients with stage IV melanoma has historically been extremely poor and there have until recently been no effective treatment options. The last 3 years have seen a seismic shift in the management of these patients with the entry to the clinic of a number of novel agents with proven efficacy. These agents fall into two main classes: molecular-targeted therapy and immunotherapy. Molecular therapies have primarily targeted the mitogen-activated protein kinase pathway, most notably with oral inhibitors targetting oncogenic BRAF. Immunotherapy agents such as ipilimumab, and more recently antibodies against PD-1 boost the host immune response against the melanoma. It is important for surgeons to be aware of these advances for a number of reasons. Firstly, to be able to inform their patients of the general options available in the event of disease progression. Secondly, these agents are currently being assessed in the adjuvant setting and are likely to demonstrate efficacy for earlier stages of disease. Finally, it is important for surgeons to be able to advocate on their patients' behalf to minimize the lag time between publication of these promising results and the availability of these agents in the clinic. Furthermore, patients with advanced melanoma should be offered participation in clinical trials in order to refine the indications for these agents to maximize their chance of benefit.

Cardiopulmonary Resuscitation Outcomes in the Emergency Department of a Comprehensive Cancer Center

Cardiopulmonary resuscitation (CPR) can be a life-saving intervention after cardiac arrest; however, the indiscriminate use of CPR among unselected populations, and particularly among those with preexisting terminal disease, confers little chance of benefit and a great possibility of harm. Cancer patients have particularly low rates of return of spontaneous circulation (ROSC) and survival to hospital discharge after CPR. An increased emphasis on palliative care for cancer patients and the incorporation of patient goals of care in planning therapeutic interventions holds the promise that CPR might be used more selectively among those with cancer, thereby resulting in higher rates of ROSC and longer-term survival after cardiac arrest. Our study objective was to determine rates of ROSC and survival to hospital discharge among cancer patients undergoing CPR in the emergency department (ED) of a comprehensive cancer center. Additionally, we examined whether these rates changed over the past decade.