A conceptual framework for cautious escalation of anticancer treatment: How to optimize overall benefit and obviate the need for de-escalation trials.

BACKGROUND: The developmental workflow of the currently performed phase 1, 2 and 3 cancer trial stages lacks essential information required for the determination of the optimal efficacy threshold of new anticancer regimens. Due to this there is a serious risk of overdosing and/or treating for an unnecessary long time, leading to excess toxicity and a higher financial burden for society. But often post-approval de-escalation trials for dose-optimization and treatment de-intensification are not performed due to failing resources and time. Therefore, the developmental workflow needs to be restructured toward cautious systemic cancer treatment escalation, in order to guarantee optimal efficacy and sustainability. METHODS: In this manuscript we discuss opportunities to produce the information needed for cautious escalation, based on models of cancer growth and cancer kill kinetics as well as exploratory biomarkers, for the purpose of designing the optimal phase 3 superiority trial. Subsequently, we compare the sample size needed for a phase 3 superiority trial, followed by a necessary de-escalation trial with the sample size needed for a multi-arm phase 3 trial with intervention arms of differing intensity. All essential items are structured within a Framework for Cautious Escalation (FCE). The discussion uses illustrations from the breast cancer setting, but aims to be applicable for all cancers. RESULTS: The FCE is a promising model of clinical development in oncology to prevent overtreatment and associated issues, especially with regard to the number of repetitive treatment cycles. It will hopefully increase the relevance and success rate of clinical trials, to deliver improved patient-centric outcomes.

Towards a novel approach guiding the decision-making process for anticancer treatment in patients with advanced cancer: framework for systemic anticancer treatment with palliative intent.

BACKGROUND: Weighing risks and benefits is currently the primary criterion for decisions regarding systemic anticancer treatment (SACT) in far advanced cancer patients, also in the modern immunotherapy- and molecular-targeted driven oncology. Decision aids rarely include substantially key concepts of early integrated palliative care (PC) and communication science. We compiled decisional factors (DFs) important for guiding the use of SACT with palliative intent (SACT-PI) and explored these DFs regarding their applicability in routine clinical care. PATIENTS AND METHODS: Clinician (participants: n = 28) and patient (n = 15) focus groups were conducted in an integrated oncology and PC setting. Thematic analysis was used to identify DFs. A Delphi survey of clinicians ranked the importance of DFs in routine decision-making. DFs were aligned with elements of the typical decision-making process, resulting in an eight-step guide for making SACT-PI decisions in clinical practice. RESULTS: Eight focus groups revealed 55 DFs relating to established topics like providing information and risk-benefit analysis, as well as to PC topics like patients' attitudes, beliefs, and hopes; patient-physician interaction; and physician attitudes. Agreement on the relative importance was reached for 34 (62%) of 55 DFs, assigned to five elements: patient/family, clinicians/system, patient-clinician-interaction, information/patient education, risk-benefit weighting/actual decision. These themes are embedded in a potential clinically useful SACT-PI Decision Framework, which includes eight steps: assess, educate, verify, reflect, discuss, weigh, pause, and decide. CONCLUSIONS: The SACT-PI Decision Framework integrates subjective patient factors, interpersonal factors, and PC issues into decision-making. Our findings complement existing decision aids and prompt lists by framing DFs in the context of SACT-PI and enforce the decision 'process', not the decision act. Further research is needed to explore the relative importance of DFs in specific patient situations and test structured decision-making processes, such as our SACT-PI Decision Framework, against standard care.

Patterns of integrating palliative care into standard oncology in an early ESMO designated center: a 10-year experience.

BACKGROUND: Integration of specialist palliative care (PC) into standard oncology care is recommended. This study investigated how integration at the Cantonal Hospital St. Gallen (KSSG) was manifested 10 years after initial accreditation as a European Society for Medical Oncology (ESMO) Designated Center (ESMO-DC) of Integrated Oncology and Palliative Care. METHODS: A chart review covering the years 2006-2009 and 2016 was carried out in patients with an incurable malignancy receiving PC. Visual graphic analysis was utilized to identify patterns of integration of PC into oncology based on the number and nature of medical consultations recorded for both specialties. A follow-up cohort collected 10 years later was analyzed and changes in patterns of integrating specialist PC into oncology were compared. RESULTS: Three hundred and forty-five patients from 2006 to 2009 and 64 patients from 2016 were included into analyses. Four distinct patterns were identified using visual graphic analysis. The 'specialist PC-led pattern' (44.9%) and the 'oncology-led pattern' (20.3%) represent disciplines that took primary responsibility for managing patients, with occasional and limited involvement from other disciplines. Patients in the 'concurrent integrated care pattern' (18.3%) had medical consultations that frequently bounced between specialist PC and oncology. In the 'segmented integrated care pattern' (16.5%), patients had sequences of continuous consultations provided by one discipline before alternating to a stretch of consultations provided by the other specialty. In the 2016 follow-up, while the 'oncology-led pattern' occurred significantly less frequently relative to the 'specialist PC-led pattern' and the 'segmented integrated care pattern', the 'concurrent integrated care pattern' emerged more frequently when compared with the 2006-2009 follow-up. CONCLUSION: The 'specialist PC-led pattern' was the most prominent pattern in this data. The 2016 follow-up showed that a growing number of patients received a collaborative pattern of care, indicating that integration of specialist PC into standard oncology can manifest as either segmented or concurrent care pathways. Our data suggest a closer, more dynamic and flexible collaboration between oncology and specialist PC early in the disease course of patients with advanced cancer and concurrent with active treatment.

Pathogen dependent effects of high amounts of oxytocin on the bloodmilk barrier integrity during mastitis in dairy cows.

INTRODUCTION: The reduction of antibiotic use in food producing animals becomes increasingly important. Therefore, suitable alternatives for mastitis treatment in dairy cows have to be considered. Oxytocin (OT) induces milk ejection and hence supports milk removal from infected mammary quarters. Beyond udder emptying, the injection of very high dosages of OT causes increased somatic cell counts (SCC) in milk and enables the transfer of immunoglobulins (Ig) from blood into milk through a reduced blood-milk barrier integrity. The aim of the present study was to investigate pathogen-specific changes of SCC, the blood derived milk components lactate dehydrogenase (LDH), serum albumin (SA), and IgG in milk of cows suffering from mastitis caused by different pathogens treated with two intravenous injections of high dosages of OT (100 IU). Milk samples from 184 dairy cows from different farms were collected on day 1 (day of clinical examination and mastitis diagnosis) and on days 2, 3, 14, and 28. Bacteriological examination (day 1) identified involved pathogens. Cows were randomly assigned to treatment (OT injections on days 1 and 2) or control group (no OT). Independently of the assigned experimental group, cows received the common therapy protocol of the veterinary practice after sample collection if the general condition was affected. Milk SCC, LDH, SA, and IgG changed specifically depending on involved pathogens. Highest values of all three parameters were measured in mastitis caused by Streptococcus uberis. Changes were less pronounced with other Streptococci spp., Staphylococci spp. or Corynebacterium bovis. Oxytocin treatment did not affect any of the studied parameters independent of the involved pathogen. Only in quarters infected with Staphylococci other than Staphylococcus aureus a decreased SCC and increased IgG concentrations in quarters, where no pathogens were detected, were observed. Thus, high dosage OT administration is obviously not suitable as a stand-alone mastitis treatment in dairy cows.

INTRODUCTION: La réduction de l'utilisation d'antibiotiques chez les animaux destinés à l'alimentation devient de plus en plus importante. Par conséquent, des alternatives appropriées au traitement des mammites chez les vaches laitières doivent être envisagées. L'ocytocine (OT) induit l'éjection du lait et favorise donc l'élimination du lait des quartiers infectés. Au-delà de la vidange de la mamelle, l'injection de doses très élevées d'OT entraîne une augmentation du nombre de cellules somatiques (CSC) dans le lait et permet le transfert d'immunoglobulines (Ig) du sang vers le lait grâce à une réduction de l'intégrité de la barrière sang-lait. Le but de la présente étude était d'étudier les changements spécifiques aux agents pathogènes du CSC, les composants du lait dérivés du sang que sont la lactate déshydrogénase (LDH) et l'albumine sérique (SA) ainsi que les IgG dans le lait de vaches souffrant de mammites causées par différents agents pathogènes traités par deux injections intraveineuses de doses élevées d'OT (100 UI). Des échantillons de lait de 184 vaches laitières de différentes exploitations ont été prélevés au jour 1 (jour de l'examen clinique et diagnostic de mammite) et aux jours 2, 3, 14 et 28. L'examen bactériologique (jour 1) a identifié les agents pathogènes impliqués. Les vaches ont été assignées au hasard au traitement (injections d'OT les jours 1 et 2) ou au groupe témoin (pas d'OT). Indépendamment du groupe auquel elles étaient attribuées, les vaches ont reçu le protocole thérapeutique usuel du cabinet vétérinaire après le prélèvement de l'échantillon si leur état général était affecté. Le CSC, la LDH, la SA et les IgG du lait ont varié spécifiquement en fonction des agents pathogènes impliqués. Les valeurs les plus élevées des trois paramètres ont été mesurées dans les mammites causées par Streptococcus uberis. Les changements étaient moins prononcés avec d'autres Streptococci spp., Staphylococci spp. ou Corynebacterium bovis. Le traitement à l'ocytocine n'a affecté aucun des paramètres étudiés indépendamment de l'agent pathogène impliqué. On a uniquement observé, dans les mammites causées par des staphylocoques autres que Staphylococcus aureus, une diminution du CSC et, dans les mammites où aucun agent pathogène n'a été détecté, une augmentation des concentrations d'IgG dans les quartiers. Ainsi, l'administration d'OT à forte dose n'est pas appropriée comme traitement unique des mammites chez les vaches laitières.

Forgiveness and Reconciliation Processes in Dying Patients With Cancer.

This article studies forgiveness and reconciliation (F/R) in patients with cancer. It focuses on the end of life, when family conflicts resurface and unfinished business challenges patients and causes spiritual distress. Forgiveness and reconciliation may intensify patient-family relationships and facilitate peace of mind and peaceful death. Existing forgiveness models and interventions focus on coping in life, yet no study has examined F/R processes until death. Our mixed-method exploratory study hypothesized that F/R processes occur in phases, repeatedly, and are spurred by approaching death. Three interdisciplinary units at a major Swiss hospital observed 50 dying patients with cancer experiencing severe conflicts with relatives, themselves, and/or with fate/God. Participant observation was combined with interpretative phenomenological analysis and descriptive statistical analysis. A semi-structured observation protocol was developed based on a 5-phase model. The protocol included space for notes (emotions, interventions, effects on dying processes). It was assessed by 20 professionals for 1 year. Analysis was supported by international interdisciplinary experts. We found that conflicts were complex and involved relational, biographical, and spiritual layers. In 62% of patients, F/R processes occurred repeatedly. Many patients died after finding F/R (22 within 48 hours). Patients indicated that imminent death, a mediating third party, acceptance, and experiences of hope motivated them to seek F/R. Although deep relationships may support F/R processes, our limited data on near-death experience/spiritual experiences restrict interpretation. Forgiveness and reconciliation processes oscillate between 5 phases: denial, crisis, experience of hope, decision, and finding F/R. Understanding F/R processes, empathy, hope, and a neutral third party may support patients in seeking forgiveness.

Addressing the quality of life needs of older patients with cancer: a SIOG consensus paper and practical guide.

Around 60% of people living with cancer are aged 65 years or older. Older cancer patients face a unique set of age-associated changes, comorbidities and circumstances that impact on their quality of life (QoL) in ways that are different from those affecting younger patients. A Task Force of the International Society of Geriatric Oncology recommends and encourages all healthcare professionals involved in cancer care to place greater focus on the QoL of older people living with cancer. This paper summarizes current thinking on the key issues of importance to addressing QoL needs of older cancer patients and makes a series of recommendations, together with practical guidance.

Fear, Pain, Denial, and Spiritual Experiences in Dying Processes.

PURPOSE: Approaching death seems to be associated with physiological/spiritual changes. Trajectories including the physical-psychological-social-spiritual dimension have indicated a terminal drop. Existential suffering or deathbed visions describe complex phenomena. However, interrelationships between different constituent factors (e.g., fear and pain, spiritual experiences and altered consciousness) are largely unknown. We lack deeper understanding of patients' inner processes to which care should respond. In this study, we hypothesized that fear/pain/denial would happen simultaneously and be associated with a transformation of perception from ego-based (pre-transition) to ego-distant perception/consciousness (post-transition) and that spiritual (transcendental) experiences would primarily occur in periods of calmness and post-transition. Parameters for observing transformation of perception (pre-transition, transition itself, and post-transition) were patients' altered awareness of time/space/body and patients' altered social connectedness. METHOD: Two interdisciplinary teams observed 80 dying patients with cancer in palliative units at 2 Swiss cantonal hospitals. We applied participant observation based on semistructured observation protocols, supplemented by the list of analgesic and psychotropic medication. Descriptive statistical analysis and Interpretative Phenomenological Analysis (IPA) were combined. International interdisciplinary experts supported the analysis. RESULTS: Most patients showed at least fear and pain once. Many seemed to have spiritual experiences and to undergo a transformation of perception only partly depending on medication. Line graphs representatively illustrate associations between fear/pain/denial/spiritual experiences and a transformation of perception. No trajectory displayed uninterrupted distress. Many patients seemed to die in peace. Previous near-death or spiritual/mystical experiences may facilitate the dying process. CONCLUSION: Approaching death seems not only characterized by periods of distress but even more by states beyond fear/pain/denial.

Characteristics of the case mix, organisation and delivery in cancer palliative care: a challenge for good-quality research.

OBJECTIVES: Palliative care (PC) services and patients differ across countries. Data on PC delivery paired with medical and self-reported data are seldom reported. Aims were to describe (1) PC organisation and services in participating centres and (2) characteristics of patients in PC programmes. METHODS: This was an international prospective multicentre study with a single web-based survey on PC organisation, services and academics and patients' self-reported symptoms collected at baseline and monthly thereafter, with concurrent registrations of medical data by healthcare providers. Participants were patients ≥18 enrolled in a PC programme. RESULTS: 30 centres in 12 countries participated; 24 hospitals, 4 hospices, 1 nursing home, 1 home-care service. 22 centres (73%) had PC in-house teams and inpatient and outpatient services. 20 centres (67%) had integral chemotherapy/radiotherapy services, and most (28/30) had access to general medical or oncology inpatient units. Physicians or nurses were present 24 hours/7 days in 50% and 60% of centres, respectively. 50 centres (50%) had professorships, and 12 centres (40%) had full-time/part-time research staff. Data were available on 1698 patients: 50% females; median age 66 (range 21-97); median Karnofsky score 70 (10-100); 1409 patients (83%) had metastatic/disseminated disease; tiredness and pain in the past 24 hours were most prominent. During follow-up, 1060 patients (62%) died; 450 (44%) <3 months from inclusion and 701 (68%) within 6 months. ANOVA and χ2 tests showed that hospice/nursing home patients were significantly older, had poorer performance status and had shorter survival compared with hospital-patients (p<.0.001). CONCLUSIONS: There is a wide variation in PC services and patients across Europe. Detailed characterisation is the first step in improving PC services and research. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01362816.

European Society for Medical Oncology (ESMO) position paper on supportive and palliative care.

Oncology has come a long way in addressing patients' quality of life, together with developing surgical, radio-oncological and medical anticancer therapies. However, the multiple and varying needs of patients are still not being met adequately as part of routine cancer care. Supportive and palliative care interventions should be integrated, dynamic, personalised and based on best evidence. They should start at the time of diagnosis and continue through to end-of-life or survivorship. ESMO is committed to excellence in all aspects of oncological care during the continuum of the cancer experience. Following the 2003 ESMO stand on supportive and palliative care (Cherny N, Catane R, Kosmidis P. ESMO takes a stand on supportive and palliative care. Ann Oncol 2003; 14(9): 1335-1337), this position paper highlights the evolving and growing gap between the needs of cancer patients and the actual provision of care. The concept of patient-centred cancer care is presented along with key requisites and areas for further work.

The 'critical mass' survey of palliative care programme at ESMO designated centres of integrated oncology and palliative care.

BACKGROUND: The ESMO Designated Centres (ESMO-DCs) of Integrated Oncology and Palliative Care (PC) Incentive Programme has grown steadily. We aimed to characterise the level of PC clinical services, education and research at ESMO-DCs. METHODS: We sent all 184 ESMO-DCs an electronic survey consisting of 78 questions examining the DC characteristics, palliative care clinical programme (structure, processes, and outcomes), primary PC delivery by oncologists, education, research and attitudes and beliefs towards the ESMO-DC programme. RESULTS: The response rate was 83% (152/184). 115 (76%) ESMO-DCs were from Europe, 87 (57%) were tertiary care centres. 136 (90%) had inpatient consultation teams, 135 (89%) had outpatient PC clinics, 107 (71%) had dedicated acute care beds, and 75 (50%) offered community-based PC. An estimated 70% (interquartile range [IQR] 28-80%) of patients with advanced cancer had a PC consultation before death, occurring 90 days before death (median, IQR 40-150 days) for outpatients and 21 days (IQR 14-45 days) for inpatients. 59 (39%) offered PC fellowship programme; 47 (32%) had mandatory PC rotations for oncology fellows. Ninety-nine (65%) had double-boarded palliative oncologists. 118 (78%) of the ESMO-DCs reported that routine symptom screening was offered in the oncology clinic and 30% of patients had documented end-of-life discussions by their oncologists. Most centres (>80%) perceived the ESMO-DC programme to increase their status. CONCLUSIONS: The ESMO-DCs had a high level of PC infrastructure and provided access to a large proportion of patients with advanced cancer. The survey supports that the 13 criteria required for ESMO designation set a robust framework for integration, stimulated investment of resources into some palliative care programmes prior to accreditation, and raised the interest about palliative care among clinicians, trainees and patients.

ESPEN expert group recommendations for action against cancer-related malnutrition.

Patients with cancer are at particularly high risk for malnutrition because both the disease and its treatments threaten their nutritional status. Yet cancer-related nutritional risk is sometimes overlooked or under-treated by clinicians, patients, and their families. The European Society for Clinical Nutrition and Metabolism (ESPEN) recently published evidence-based guidelines for nutritional care in patients with cancer. In further support of these guidelines, an ESPEN oncology expert group met for a Cancer and Nutrition Workshop in Berlin on October 24 and 25, 2016. The group examined the causes and consequences of cancer-related malnutrition, reviewed treatment approaches currently available, and built the rationale and impetus for clinicians involved with care of patients with cancer to take actions that facilitate nutrition support in practice. The content of this position paper is based on presentations and discussions at the Berlin meeting. The expert group emphasized 3 key steps to update nutritional care for people with cancer: (1) screen all patients with cancer for nutritional risk early in the course of their care, regardless of body mass index and weight history; (2) expand nutrition-related assessment practices to include measures of anorexia, body composition, inflammatory biomarkers, resting energy expenditure, and physical function; (3) use multimodal nutritional interventions with individualized plans, including care focused on increasing nutritional intake, lessening inflammation and hypermetabolic stress, and increasing physical activity.

ESPEN guidelines on nutrition in cancer patients

Cancers are among the leading causes of morbidity and mortality worldwide, and the number of new cases is expected to rise significantly over the next decades. At the same time, all types of cancer treatment, such as surgery, radiation therapy, and pharmacological therapies are improving in sophistication, precision and in the power to target specific characteristics of individual cancers. Thus, while many cancers may still not be cured they may be converted to chronic diseases. All of these treatments, however, are impeded or precluded by the frequent development of malnutrition and metabolic derangements in cancer patients, induced by the tumor or by its treatment. These evidence-based guidelines were developed to translate current best evidence and expert opinion into recommendations for multi-disciplinary teams responsible for identification, prevention, and treatment of reversible elements of malnutrition in adult cancer patients. The guidelines were commissioned and financially supported by ESPEN and by the European Partnership for Action Against Cancer (EPAAC), an EU level initiative. Members of the guideline group were selected by ESPEN to include a range of professions and fields of expertise. We searched for meta-analyses, systematic reviews and comparative studies based on clinical questions according to the PICO format. The evidence was evaluated and merged to develop clinical recommendations using the GRADE method. Due to the deficits in the available evidence, relevant still open questions were listed and should be addressed by future studies. Malnutrition and a loss of muscle mass are frequent in cancer patients and have a negative effect on clinical outcome. They may be driven by inadequate food intake, decreased physical activity and catabolic metabolic derangements. To screen for, prevent, assess in detail, monitor and treat malnutrition standard operating procedures, responsibilities and a quality control process should be established at each institution involved in treating cancer patients. All cancer patients should be screened regularly for the risk or the presence of malnutrition. In all patients - with the exception of end of life care - energy and substrate requirements should be met by offering in a step-wise manner nutritional interventions from counseling to parenteral nutrition. However, benefits and risks of nutritional interventions have to be balanced with special consideration in patients with advanced disease. Nutritional care should always be accompanied by exercise training. To counter malnutrition in patients with advanced cancer there are few pharmacological agents and pharmaconutrients with only limited effects. Cancer survivors should engage in regular physical activity and adopt a prudent diet.

The effect of real-time electronic monitoring of patient-reported symptoms and clinical syndromes in outpatient workflow of medical oncologists: E-MOSAIC, a multicenter cluster-randomized phase III study (SAKK 95/06).

BACKGROUND: Patients with advanced, incurable cancer receiving anticancer treatment often experience multidimensional symptoms. We hypothesize that real-time monitoring of both symptoms and clinical syndromes will improve symptom management by oncologists and patient outcomes. PATIENTS AND METHODS: In this prospective multicenter cluster-randomized phase-III trial, patients with incurable, symptomatic, solid tumors, who received new outpatient chemotherapy with palliative intention, were eligible. Immediately before the weekly oncologists' visit, patients completed the palm-based E-MOSAIC assessment (Edmonton-Symptom-Assessment-Scale, ≤3 additional symptoms, estimated nutritional intake, body weight change, Karnofsky Performance Status, medications for pain, fatigue, nutrition). A cumulative, longitudinal monitoring sheet (LoMoS) was printed immediately. Eligible experienced oncologists were defined as one cluster each and randomized to receive the immediate print-out LoMoS (intervention) or not (control). Primary analysis limited to patients having uninterrupted (>4/6 visits with same oncologist) patient-oncologist sequences was a mixed model for the difference in patients global quality of life (G-QoL; items 29/30 of EORTC-QlQ-c30) between baseline (BL) and week 6. Intention-to-treat (ITT) analysis included all eligible patients. RESULTS: In 8 centers, 82 oncologists treated 264 patients (median 66 years; overall survival intervention 6.3, control 5.4 months) with various tumors. The between-arm difference in G-QoL of 102 uninterrupted patients (intervention: 55; control: 47) was 6.8 (P = 0.11) in favor of the intervention; in a sensitivity analysis (oncologists treating ≥2 patients; 50, 39), it was 9.0 (P = 0.07). ITT analysis revealed improvement in symptoms (difference last study visit-BL: intervention -5.4 versus control 2.1, P = 0.003) and favored the intervention for communication and coping. More patients with high symptom load received immediate symptom management (chart review, nurse-patient interview) by oncologists getting the LoMoS. CONCLUSION: Monitoring of patient symptoms, clinical syndromes and their management clearly reduced patients' symptoms, but not QoL. Our results encourage the implementation of real-time monitoring in the routine workflow of oncologist with a computer solution.

Assessment of anticancer-treatment outcome in patients with metastatic castration-resistant prostate cancer-going beyond PSA and imaging, a systematic literature review.

BACKGROUND: In the past years, there has been significant progress in anticancer drug development for patients with metastatic castration-resistant prostate cancer (CRPC). However, the current instruments to assess clinical treatment response have limitations and may not sufficiently reflect patient benefit. Our objective was to systematically identify tools to evaluate both patient benefit and clinical anticancer-treatment response as basis for an international consensus process and development of a specific pragmatic instrument for men with CRPC. METHODS: PubMed, Embase and CINAHL were searched to identify currently available tools to assess anticancer-treatment benefit, other than standard imaging procedures and prostate-specific antigen measurements, namely quality of life (QoL), detailed pain assessment, physical function and objective measures of other complex cancer-related syndromes in patients with CRPC. Additionally, all CRPC phase III trials published in the last 5 years were reviewed as well as studies using physical function tools in a general cancer population. The PRIMSA statement was followed for the systematic review process. RESULTS: The search generated 1096 hits, 185 full-text papers were screened and finally 73 publications were included. Additional 89 publications were included by hand-search. We identified a total of 98 tools used in CRPC trials and grouped these into three categories: 22 tools assessing QoL domains and subgroups, 47 tools for pain assessment and 29 tools for objective measures, mainly physical function and assessment of skeletal disease burden. CONCLUSION: A wide variety of assessment tools and also efforts to standardize and harmonize patient-reported outcomes and pain assessment were identified. However, the specific needs of the increasing CRPC population living longer with their incurable cancer are insufficiently captured and objective physical outcome measures are under-represented. In the age of new anticancer drug targets and principles, new methods to monitor patient relevant outcomes of antineoplastic therapy are of utmost importance.

Best supportive care in clinical trials: review of the inconsistency in control arm design.

BACKGROUND: Best supportive care (BSC) as a control arm in clinical trials is poorly defined. We conducted a review to evaluate clinical trials' concordance with published, consensus-based framework for BSC delivery in trials. METHODS: A consensus-based Delphi panel previously identified four key domains of BSC delivery in trials: multidisciplinary care; supportive care documentation; symptom assessment; and symptom management. We reviewed trials including BSC control arms from 2002 to 2014 to assess concordance to BSC standards and to selected items from the CONSORT 2010 guidelines. RESULTS: Of 408 articles retrieved, we retained 18 after applying exclusion criteria. Overall, trials conformed to the CONSORT guidelines better than the BSC standards (28% vs 16%). One-third of articles offered a detailed description of BSC, 61% reported regular symptom assessment, and 44% reported using validated symptom assessment measures. One-third reported symptom assessment at identical intervals in both arms. None documented evidence-based symptom management. No studies reported educating patients about symptom management or goals of therapy. No studies reported offering access to palliative care specialists. CONCLUSIONS: Reporting of BSC in trials is incomplete, resulting in uncertain internal and external validity. Such studies risk systematically over-estimating the net clinical effect of the comparator arms.

Indicators of integration of oncology and palliative care programs: an international consensus.

BACKGROUND: Recently, the concept of integrating oncology and palliative care has gained wide professional and scientific support; however, a global consensus on what constitutes integration is unavailable. We conducted a Delphi Survey to develop a consensus list of indicators on integration of specialty palliative care and oncology programs for advanced cancer patients in hospitals with ≥100 beds. METHODS: International experts on integration rated a list of indicators on integration over three iterative rounds under five categories: clinical structure, processes, outcomes, education, and research. Consensus was defined a priori by an agreement of ≥70%. Major criteria (i.e. most relevant and important indicators) were subsequently identified. RESULTS: Among 47 experts surveyed, 46 (98%), 45 (96%), and 45 (96%) responded over the three rounds. Nineteen (40%) were female, 24 (51%) were from North America, and 14 (30%) were from Europe. Sixteen (34%), 7 (15%), and 25 (53%) practiced palliative care, oncology, and both specialties, respectively. After three rounds of deliberation, the panelists reached consensus on 13 major and 30 minor indicators. Major indicators included two related to structure (consensus 95%-98%), four on processes (88%-98%), three on outcomes (88%-91%), and four on education (93%-100%). The major indicators were considered to be clearly stated (9.8/10), objective (9.4/10), amenable to accurate coding (9.5/10), and applicable to their own countries (9.4/10). CONCLUSIONS: Our international experts reached broad consensus on a list of indicators of integration, which may be used to identify centers with a high level of integration, and facilitate benchmarking, quality improvement, and research.