Using three scenarios to explain life expectancy in advanced cancer: attitudes of patients, family members, and other healthcare professionals.

AIM: To evaluate a web-based tool for estimating and explaining three scenarios for expected survival time to people with advanced cancer (patients), their family members (FMs), and other healthcare professionals (HCPs). METHODS: Thirty-three oncologists estimated the "median survival of a group of similar patients" for patients seeking quantitative prognostic information. The web-based tool generated worst-case, most likely, and best-case scenarios for survival based on the oncologist's estimate. Oncologists presented the scenarios to each patient and provided a printed summary to patients, FMs, and HCPs. Attitudes to the information were assessed by questionnaires. Observed survival for each patient was compared with the oncologist's estimated survival and the three scenarios. RESULTS: Prognosis was discussed with 222 patients: median age 67 years; 61% male; most common primary sites pancreas 15%, non-small-cell lung 15%, and colorectal 12%. The median (range) for observed survival times was 9 months (0.5-43) and for oncologist's estimated survival times was 12 months (2-96). Ninety-one percent of patients, 91% of FMs, and 84% of HCPs agreed that it was helpful having life expectancy explained as three scenarios. The majority (77%) of patients judged the information presented about their life expectancy to be the same or better than they had expected before the consultation. The survival estimates met a priori criteria for calibration, precision, and accuracy. CONCLUSIONS: Patients, FMs, and HCPs found it helpful to receive personalized prognostic information formatted as three scenarios for survival. It was feasible, acceptable, and safe to use a web-based resource to do this.

On the receiving end: have patient perceptions of the side-effects of cancer chemotherapy changed since the twentieth century?

BACKGROUND: Studies in 1983 and 1993 identified and ranked symptoms experienced by cancer patients receiving chemotherapy. We repeated the studies to obtain updated information on patient perceptions of chemotherapy-associated symptoms. PATIENTS AND METHODS: A cross-sectional interview and patient-reported outcome questionnaires were administered to out-patients receiving chemotherapy. Patients selected from 124 cards to identify and rank the severity of physical and non-physical symptoms they had experienced and attributed to chemotherapy (primary endpoint). The patient's medical oncologist and primary chemotherapy nurse were invited to rank the five symptoms they believed the patient would rank as their most severe. We analysed the association of symptoms and their severity with patient demographics, chemotherapy regimen, and patient-reported outcomes. Results were compared to the earlier studies. RESULTS: Overall, 302 patients completed the interview: median age 58 years (range 17-85); 56% female; main tumour types colorectal 81 (27%), breast 67 (22%), lung 49 (16%); 45% treated with curative intent. Most common symptoms (reported by >50%) were: alopecia, general weakness, effects on family/partner, loss of taste, nausea, fatigue, difficulty sleeping, effects on work/home duties, and having to put life on hold. The most severe symptoms (ranked by >15% in top five) were: concern about effects on family/partner, nausea, fear of the future, fatigue, not knowing what will happen, putting my life on hold, and general weakness. Perceptions of doctors and nurses of patients' symptom severity closely matched patients' rankings. CONCLUSIONS: Compared to earlier studies, there was an increase in non-physical concerns such as effects on family and future, and a decrease in physical symptoms, particularly vomiting, but nausea, fatigue and general weakness remained bothersome. HIGHLIGHTS: • Symptoms related to chemotherapy have changed over time, likely due to less toxic regimens and improvements in supportive care. • Effects on family/partner, fear of the future, not knowing what will happen, and "life on hold" were major issues for patients. • Vomiting has decreased but nausea, fatigue and general weakness remain common symptoms for chemotherapy patients.

Preferences for life expectancy discussions following diagnosis with a life-threatening illness: a discrete choice experiment.

PURPOSE: To explore in a sample of adult cancer patients: (1) the relative influence of initiation source, information format and consultation format on preferred approach to life expectancy disclosure using a discrete choice experiment (DCE); and (2) whether patient age, cancer type and perceived prognosis were associated with preferences within the three attributes. METHODS: A DCE survey of adult solid tumour and haematological cancer patients. Participants chose between three hypothetical scenarios about life expectancy disclosure consisting of three attributes: initiation source (i.e. doctor versus patient-initiated discussion), information content (i.e. estimate presented as best-worst-typical length of life case scenario versus median survival time) and consultation format (i.e. two 20-min versus one 40-min consultation). Respondents selected their most preferred scenario within each question. RESULTS: Three hundred and two patients completed the DCE (78% consent rate). Initiation source was the most influential predictor of patient choice. More preferred a doctor deliver life expectancy information as soon as it is available rather than waiting for the patient to ask (59% vs 41% z = - 7.396, p < 0.01). More patients preferred the two 20-min rather than the one 40-min consultation format (55% vs 45%, z = 4.284, p < 0.01). Information content did not influence choice. Age, cancer type, and patient-perceived prognosis were not associated with preferences. CONCLUSION: Healthcare professionals should assess cancer patients' preferences for engaging in life expectancy discussions as soon as they have this information, and ensure patients have adequate time to consider the information they receive, seek additional information and involve others if they wish.

PD-1 blockade using pembrolizumab in adolescent and young adult patients with advanced bone and soft tissue sarcoma.

BACKGROUND: Sarcomas represent 10%-15% of cancers in adolescent and young adult (AYA) patients, and survival for those with metastatic disease or relapse is poor. Immunotherapy with checkpoint inhibition has improved outcomes in multiple tumor types, but data in advanced sarcomas, particularly within the AYA population, are limited. AIM: We aim to evaluate response and toxicity for AYA patients with sarcoma treated with pembrolizumab. METHODS AND RESULTS: We retrospectively reviewed AYA patients with advanced bone and soft tissue sarcoma who received self-funded pembrolizumab between May 2015 and January 2019. Eighteen patients were identified. One patient with Ewing sarcoma had a sustained complete response to therapy. Two patients with alveolar soft part sarcoma received a clinical benefit from pembrolizumab: one had a radiological partial response with an excellent clinical response and one patient achieved stable disease. Four patients died of disease prior to first scheduled assessment and thus were not evaluable. The remaining eleven patients had progressive disease. CONCLUSION: The role of immunotherapy in AYA sarcoma warrants further investigation. Biomarkers of response need to be further evaluated in order to guide patient selection.

Fidelity is fundamental: intervention predictors in advance care plans in terminal cancer.

OBJECTIVES: Assessing whether interventions are implemented as intended (fidelity) is critical to establishing efficacy in clinical research yet rarely applied in advance care planning (ACP) interventions. We aimed to develop and implement a fidelity audit tool for an ACP intervention. METHODS: We developed a fidelity audit tool assessing: (A) content; (B) quality (general communication, eliciting EOL preferences and prognostic communication); and (C) family/caregiver involvement. We audited (double-coded) 55 audio-recordings of ACP discussions delivered to advanced cancer patients and caregivers, within a clinical trial. RESULTS: Fidelity to content was high: mean=9.38/11 but lower for the quality of general communication (mean=12.47/20), discussion of patient preferences (mean=4.67/7), prognosis (mean=3.9/6) and family/caregiver involvement (mean=2.67/4). Older patient age and caregiver religiosity were associated with higher fidelity. Higher fidelity to content was associated with the trial primary outcome of family caregiver report of patient wishes being discussed and met. CONCLUSIONS: Fidelity to content, but not quality, of the ACP intervention is strong. Communication skills training is critical for ACP interventionists. Adherence was higher with older patients and religious carers, factors that may influence acceptance of death and readiness to undertake ACP, making the discussion easier. TRIAL REGISTRATION NUMBER: ACTRN12613001288718.

Cediranib in patients with alveolar soft-part sarcoma (CASPS): a double-blind, placebo-controlled, randomised, phase 2 trial.

BACKGROUND: Alveolar soft-part sarcoma (ASPS) is a rare soft-tissue sarcoma that is unresponsive to chemotherapy. Cediranib, a tyrosine-kinase inhibitor, has shown substantial activity in ASPS in non-randomised studies. The Cediranib in Alveolar Soft Part Sarcoma (CASPS) study was designed to discriminate the effect of cediranib from the intrinsically indolent nature of ASPS. METHODS: In this double-blind, placebo-controlled, randomised, phase 2 trial, we recruited participants from 12 hospitals in the UK (n=7), Spain (n=3), and Australia (n=2). Patients were eligible if they were aged 16 years or older; metastatic ASPS that had progressed in the previous 6 months; had an ECOG performance status of 0-1; life expectancy of more than 12 weeks; and adequate bone marrow, hepatic, and renal function. Participants had to have no anti-cancer treatment within 4 weeks before trial entry, with exception of palliative radiotherapy. Participants were randomly assigned (2:1), with allocation by use of computer-generated random permuted blocks of six, to either cediranib (30 mg orally, once daily) or matching placebo tablets for 24 weeks. Treatment was supplied in number-coded bottles, masking participants and clinicians to assignment. Participants were unblinded at week 24 or sooner if they had progression defined by Response Evaluation Criteria in Solid Tumors (version 1.1); those on placebo crossed over to cediranib and all participants continued on treatment until progression or death. The primary endpoint was percentage change in sum of target marker lesion diameters between baseline and week 24 or progression if sooner, assessed in the evaluable population (all randomly assigned participants who had a scan at week 24 [or sooner if they progressed] with target marker lesions measured). Safety was assessed in all participants who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT01337401; the European Clinical Trials database, number EudraCT2010-021163-33; and the ISRCTN registry, number ISRCTN63733470 recruitment is complete and follow-up is ongoing. FINDINGS: Between July 15, 2011, and July 29, 2016, of 48 participants recruited, all were randomly assigned to cediranib (n=32) or placebo (n=16). 23 (48%) were female and the median age was 31 years (IQR 27-45). Median follow-up was 34·3 months (IQR 23·7-55·6) at the time of data cutoff for these analyses (April 11, 2018). Four participants in the cediranib group were not evaluable for the primary endpoint (one did not start treatment, and three did not have their scan at 24 weeks). Median percentage change in sum of target marker lesion diameters for the evaluable population was -8·3% (IQR -26·5 to 5·9) with cediranib versus 13·4% (IQR 1·1 to 21·3) with placebo (one-sided p=0·0010). The most common grade 3 adverse events on (blinded) cediranib were hypertension (six [19%] of 31) and diarrhoea (two [6%]). 15 serious adverse reactions in 12 patients were reported; 12 of these reactions occurred on open-label cediranib, and the most common symptoms were dehydration (n=2), vomiting (n=2), and proteinuria (n=2). One probable treatment-related death (intracranial haemorrhage) occurred 41 days after starting open-label cediranib in a patient who was assigned to placebo in the masked phase. INTERPRETATION: Given the high incidence of metastatic disease and poor long-term prognosis of ASPS, together with the lack of efficacy of conventional chemotherapy, our finding of significant clinical activity with cediranib in this disease is an important step towards the goal of long-term disease control for these young patients. Future clinical trials in ASPS are also likely to involve immune checkpoint inhibitors. FUNDING: Cancer Research UK and AstraZeneca.

FISH analysis of selected soft tissue tumors: Diagnostic experience in a tertiary center.

AIM: Fluorescence in situ hybridization (FISH) is an important ancillary tool for the classification of bone/soft tissue (BST) tumors. The aim of this study was to evaluate the contribution of FISH to the final classification of common BST entities in the molecular pathology department of the Royal Prince Alfred Hospital (RPAH), which is one of the most important referral centers for the management of sarcomas in Australia. METHODS: All routine diagnostic FISH tests performed on BST formalin-fixed paraffin embedded (FFPE) tissue specimens at the RPAH in a 5-year period (February, 2010-November, 2015) were reviewed. FISH analyses presented in this study include commercial break-apart probes (SS18, FUS, DDIT3, FUS, USP6, PDGFB, TFE3 and ALK) and a single enumeration (MDM2) probe. RESULTS: There were 434 interpretable FISH assays on BST samples including MDM2 (n=180), SS18 (n=97), FUS (n=64), DDIT3 (n=37), USP6 (n=30), PDGFB (n=13), TFE3 (n=8) and ALK (n=5). Discrepancies between the histopathological diagnosis and the FISH results were seen in 12% of the cases. In this subset of discordant cases, FISH contributed to the re-classification of 7% of cases originally diagnosed as synovial sarcoma (SS18) and 6% of adipocytic neoplasms (MDM2) based on the presence or absence of the expected gene alteration. CONCLUSION: Our study confirms that paraffin FISH is a sensitive and specific ancillary tool in the diagnosis of BST neoplasms when used in the appropriate clinicopathological context. These findings highlight the need for further ancillary molecular tools in the diagnosis and characterization of challenging cases.

A randomised controlled trial of an advance care planning intervention for patients with incurable cancer.

BACKGROUND: We modified and evaluated an advance care planning (ACP) intervention, which had been shown to improve compliance with patient's end of life (EoL) wishes, in a different patient population. METHODS: Patients with incurable cancer, and a Family Member (FM), were randomised one-to-one to usual care or usual care plus an ACP intervention, between April 2014 and January 2017. Oncologists and participants were non-blinded. ACP was based on the Respecting Patient Choices model, with an offer to provide individualised ranges for typical, best-case and worst-case scenarios for survival time. Seven facilitators (two oncology nurses, two nurses and three allied health professionals) delivered the intervention within 2 weeks of study enrolment. The primary outcome measure, assessed by interviewing the FM 3 months after patient death, was the FM perception that the patient's wishes were discussed, and met. RESULTS: Six hundred and sixty-five patients from seven Australian metropolitan oncology centres were referred for consideration by their oncologists, 444 (67%) met the study inclusion criteria and were approached by a study researcher. Two hundred and eight patients (47%) and their FM entered the trial as dyads. Fifty-three (46%) dyads in the ACP group and 63 (54%) dyads in the usual-care group had complete primary outcome data (p = 0.16). Seventy-nine patients and 53 FMs attended an ACP discussion. Mean length of discussion was 57 min. FMs from 23 (43%) dyads allocated to ACP and 21 (33%) dyads allocated usual care reported the patient's EoL wishes were discussed and met (difference 10%, 95% CI: -2 to 8, p = 0.27). There were no differences in EoL care received, patient satisfaction with care; FM satisfaction with care or with death; or FM well being. Rates of palliative care referral were high in both groups (97% vs 96%). CONCLUSIONS: A formal ACP intervention did not increase the likelihood that EoL care was consistent with patients' preferences.

Supporting doctor-patient communication: Providing a question prompt list and audio recording of the consultation as communication aids to outpatients in a cancer clinic.

OBJECTIVE: To document the effect of a cancer specific question prompt list (QPL) on patients question asking and shared decision-making (SDM), and to evaluate the combined effect of the QPL and consultation audio recording (CAR) on patient outcomes. METHOD: This exploratory study compared two groups of patients receiving either a QPL or combined QPL/CAR, to a control group. Measurements included number/types of questions asked, and physician SDM behavior (OPTION score). Questionnaire data included anxiety/depression and quality of life (QoL). RESULTS: A total of 93 patients participated (31 Control, 30 QPL and 32 Combined). Patients in the intervention groups asked more questions concerning prognosis (p < .0001), the disease (p = .006) and quality of treatment (p < .001) than patients in the control group, but no impact was found on the OPTION score. An increase in mean consultation length was observed in the intervention groups compared to the control group (44 vs. 36 min; p = .028). Patients rated both interventions positively. CONCLUSION: Provision of the QPL facilitates patients to ask a broader range of questions, but does not increase physician SDM behavior. PRACTICAL IMPLEMENTATION: The combination of QPL and CAR seems feasible and should be tested in an implementation study following the disease trajectory.

Nilotinib in locally advanced pigmented villonodular synovitis: a multicentre, open-label, single-arm, phase 2 trial.

BACKGROUND: Pigmented villonodular synovitis (alternatively known as diffuse-type giant cell tumour) is a rare, locally aggressive tumour driven by a specific translocation resulting in the overexpression of colony-stimulating factor 1 (CSF1). CSF1 receptor (CSF1R) inhibitors (ie, tyrosine kinase inhibitors and antibodies) induce a response in patients with pigmented villonodular synovitis. We investigated the safety and efficacy of a CSF1R tyrosine kinase inhibitor, nilotinib, in patients with locally advanced non-resectable pigmented villonodular synovitis. METHODS: In this phase 2, open-label, single-arm study, we enrolled patients from 11 cancer centres of hospitals in four countries (France, Netherlands, Italy, and Australia). Eligible patients were aged at least 18 years with a WHO performance status of 2 or less, and histologically confirmed progressive or relapsing pigmented villonodular synovitis that was inoperable, or resectable only with mutilating surgery. Patients received oral nilotinib (400 mg twice per day) until disease progression, unacceptable toxicity, or completion of 1 year of treatment. The primary endpoint was the proportion of patients who were progression free at 12 weeks, which was centrally assessed according to Response Evaluation Criteria in Solid Tumors version 1.1. Analyses were by modified intention to treat (ie, all patients with no major protocol violations who were treated with nilotinib for at least 3 weeks were included). All participants who received at least one dose of study drug were included in the safety analyses. This study is registered with ClinicalTrials.gov, number NCT01261429, and the results presented here are the final analysis of the trial. FINDINGS: Between Dec 15, 2010, and Sept 28, 2012, we enrolled 56 patients with pigmented villonodular synovitis and treated them with nilotinib. Five (9%) patients discontinued study treatment before week 12; therefore, 51 patients were evaluable for the primary endpoint at 12 weeks. The estimated proportion of patients who were progression free at 12 weeks was 92·6% (95% credible interval 84·3-97·9). 54 (96%) of 56 patients had a treatment-related adverse event. Six (11%) of 56 patients had at least one grade 3 treatment-related adverse event (headache, dizziness, and hepatic disorders [n=1], pruritus and toxidermia [n=1], diarrhoea [n=1], increased γ-glutamyl transferase concentration [n=1], anorexia [n=1], and increased headache [n=1]). No grade 4 or 5 adverse events were reported. One patient had a treatment-related serious adverse event (toxidermia) and two patients had serious adverse events not considered to be related to the study drug (borderline ovarian tumour [n=1] and pilonidal cyst excision [n=1]). INTERPRETATION: More than 90% of patients with locally advanced unresectable progressive pigmented villonodular synovitis achieved disease control with 12 weeks of nilotinib treatment. These results indicate that CSF1R tyrosine kinase inhibitors have anti-tumour activity with manageable toxicity in patients with inoperable progressive pigmented villonodular synovitis. Randomised trials investigating the efficacy of nilotinib for patients with unresectable pigmented villonodular synovitis are warranted. FUNDING: Novartis, Institut National du Cancer, EuroSARC, French National Cancer Institute, General Directorate of Care Supply, Lyon Research Innovation for Cancer, L'Agence nationale de la recherche, Laboratory of Excellence, Fondation ARC pour la recherche sur le cancer, Ligue contre le Cancer (comité de l'Ain), Info Sarcomes, and Association DAM'S.

Development and Pilot Testing of a Decision Aid for Genomic Research Participants Notified of Clinically Actionable Research Findings for Cancer Risk.

Germline genomic testing is increasingly used in research to identify genetic causes of disease, including cancer. However, there is evidence that individuals who are notified of clinically actionable research findings have difficulty making informed decisions regarding uptake of genetic counseling for these findings. This study aimed to produce and pilot test a decision aid to assist participants in genomic research studies who are notified of clinically actionable research findings to make informed choices regarding uptake of genetic counseling. Development was guided by published literature, the International Patient Decision Aid Standards, and the expertise of a steering committee of clinicians, researchers, and consumers. Decision aid acceptability was assessed by self-report questionnaire. All 19 participants stated that the decision aid was easy to read, clearly presented, increased their understanding of the implications of taking up research findings, and would be helpful in decision-making. While low to moderate levels of distress/worry were reported after reading the booklet, a majority of participants also reported feeling reassured. All participants would recommend the booklet to others considering uptake of clinically actionable research findings. Results indicate the decision aid is acceptable to the target audience, with potential as a useful decision support tool for genomic research participants.

How Well Do Current Measures Assess the Impact of Advance Care Planning on Concordance Between Patient Preferences for End-of-Life Care and the Care Received: A Methodological Review.

BACKGROUND: Research has begun to focus on whether Advance Care Planning (ACP) has the capacity to influence care, and to examine whether ACP can be effective in meeting patients' wishes at the end of their lives. Little attention has been paid, however, to the validity and clinical relevance of existing measures. METHODS: A search of Medline and CINHAL identified ACP studies measuring concordance between end-of-life (EoL) preferences and the care received. Databases were searched from 2000 to August 2016. We developed a checklist to evaluate the quality of included studies. Data were collected on the proportion of patients who received concordant care, extracted from manuscript tables or calculated from the text. OUTCOMES: Of 2941 papers initially identified, nine eligible studies were included. Proportions of patients who received concordant care varied from 14% to 98%. Studies were heterogeneous and methodologically poor, with limited attention paid to bias/external validity. Studies varied with regards to design of measures, the meaning of relevant terms like "preference" "EoL care" and "concordance," and the completeness of reported data. CONCLUSION: Methodological variations and weaknesses compromise the validity of study results, and prevent meaningful comparisons between studies or synthesis of the results. Effectively evaluating whether ACP interventions enhance a patient's capacity to receive the care they want requires harmonization of research. This demands standardization of methods across studies, validating of instruments, and consensus based on a consistent conceptual framework regarding what constitutes a meaningful outcome measure.

Patient autonomy and advance care planning: a qualitative study of oncologist and palliative care physicians' perspectives.

IMPORTANCE: Patients' are encouraged to participate in advance care planning (ACP) in order to enhance their autonomy. However, controversy exists as to what it means to be autonomous and there is limited understanding of how social and structural factors may influence cancer patients' ability to exercise their autonomy. OBJECTIVE: The objective of this study is to explore oncologists' and palliative care physicians' understanding of patient autonomy, how this influences reported enactment of decision-making at the end of life (EOL), and the role of ACP in EOL care. DESIGN AND SETTING: Qualitative semi-structured interviews were conducted with consultant oncologists (n = 11) and palliative medicine doctors (n = 7) working in oncology centres and palliative care units across Australia. RESULTS: We found that doctors generally conceptualized autonomy in terms of freedom from interference but that there was a profound disconnect between this understanding of autonomy and clinical practice in EOL decision-making. The clinicians in our study privileged care, relationships and a 'good death' above patient autonomy, and in practice were reluctant to 'abandon' their patients to total non-interference in decision-making. Patient autonomy in healthcare is bounded, as while patients were generally encouraged to express their preferences for care, medical norms about the quality and 'reasonableness' of care, the availability of services and the patients' family relationships act to enhance or limit patients' capacity to realize their preferences. While for many, this disconnect between theory and practice did not diminish the rhetorical appeal of ACP; for others, this undermined the integrity of ACP, as well as its relevance to care. For some, ACP had little to do with patient autonomy and served numerous other ethical, practical and political functions. CONCLUSION: The ethical assumptions regarding patient autonomy embedded in academic literature and policy documents relating to ACP are disconnected from the realities of clinical care. Medical norms and professional boundaries surrounding 'good deaths' have a greater influence on care than patient preference. ACP programs, therefore, may be rejected by healthcare professionals as irrelevant to care or may have the unintended consequence of limiting patient autonomy when used as a professional tool to encourage a 'right' way to die. A singular focus on bureaucratic ACP programs, which reduce patient autonomy to a 'tick box' exercise, may fail to enhance EOL care in any meaningful way.

What do patients with cancer and their families value most at the end of life? A critical analysis of advance care planning.

BACKGROUND: Advance care planning (ACP) is defined in a variety of ways, although it is widely understood as a process undertaken by patients, when they have capacity, to define and communicate their treatment preferences for future care. Few studies have explored the meaning and importance patients place on their ability to participate in directing their medical care. AIM: This study aimed to explore how cancer patients and their family members value autonomy at the end of life (EoL) and understand how this may impact on the way they develop and act on EoL decisions and planning. METHODS: Data were collected through in-depth semi-structured interviews with patients and family members of people with cancer. Participants were recruited from metropolitan cancer centres in Sydney, Australia. Interviews were analysed using thematic analysis. FINDINGS: Findings from 11 participant interviews (five patients with cancer and six family members) were organised into four themes: 'the threat of death and cancer'; 'patients seek trust and safety at the end of life'; 'doctors are human and the healthcare system has limitations'; and 'the role of ACP'. Participants experienced cancer and death as a 'threat', to self and others and as something 'uncontrollable'. ACP was seen to have the potential to enhance EoL care by contributing to decreasing uncertainty, enhancing comfort, helping to achieve 'the small things', and in helping the family 'know what to do'. However, participants were, in general, distrustful of documentation and cognisant of uncertainty around medical outcomes and the legal limitations of their capacity to influence care. CONCLUSIONS: These findings suggest that models of ACP which are constructed around patients' 'rights' to determine what happens to their bodies may do little to enhance the quality of EoL care, as patients value veracity, trust and comfort at the EoL more than autonomy. Quality EoL care should focus on paying increased attention to the relational and social aspects of care.

"Standard Care" in Cancer Clinical Trials: An Analysis of Care Provided to Women in the Control Arms of Breast Cancer Clinical Trials.

Background: For trials to validly evaluate new treatments, comparison against the best existing alternative treatment is essential. We reviewed the care provided to women in control arms of breast cancer clinical trials to estimate the proportion consistent with the standard of care as defined in clinical guidelines. Methods: We analyzed phase III randomized controlled breast cancer trials comparing drug treatments with "standard care," enrolling between 2004 and 2014, and registered on ClinicalTrials.gov Our primary outcome was the proportion of trials in which treatment in the control arm was consistent with concurrent NCCN Guidelines. A secondary analysis assessed trials recruiting outside the United States that provided control group therapy not consistent with NCCN Guidelines, comparing them with the German Gynecological Oncology Group (AGO) guidelines. We assessed associations between the primary outcome and a priori selected trial characteristics. Results: This study included 210 trials that recruited 229,182 women worldwide; 29% of trials (60/210) did not provide control group treatment that was consistent with NCCN Guidelines. For trials not recruiting in the United States, results were similar; in 21% of trials, control arm treatment was inconsistent with both AGO and NCCN Guidelines. Factors significantly associated with offering control arm treatment that were inconsistent with guidelines were time period (later trials were less likely to be consistent), breast cancer stage and type (trials in early-stage breast cancer and estrogen receptor-negative disease were less likely consistent), and recruitment in ≥4 countries and recruitment outside the United States. Conclusions: To ensure that clinical trials achieve their goal of obtaining the best information to guide patient treatment, the question of how investigators chose and describe "standard care" for control arm participants warrants further investigation.