Time estimates in prognostic discussions: A conversation analytic study of hospice multidisciplinary team meetings.

BACKGROUND: Recommendations state that multidisciplinary team expertise should be utilised for more accurate survival predictions. How the multidisciplinary team discusses prognoses during meetings and how they reference time, is yet to be explored. AIM: To explore how temporality is conveyed in relation to patients' prognoses during hospice multidisciplinary team meetings. DESIGN: Video-recordings of 24 hospice multidisciplinary team meetings were transcribed and analysed using Conversation Analysis. SETTING/PARTICIPANTS: A total of 65 staff participating in multidisciplinary team meetings in a UK hospice from May to December 2021. RESULTS: Team members conveyed temporality in three different ways. (i) Staff stated that a patient was dying as part of the patient's current health status. These formulations did not include a time reference per se but described the patient's current situation (as dying) instead. (ii) Staff used specific time period references where another specific reference had been provided previously that somehow constrained the timeframe. In these cases, the prognosis would conflict with other proposed care plans. (iii) Staff members used unspecific time period references where the reference appeared vague and there was greater uncertainty about when the patient was expected to die. CONCLUSIONS: Unspecific time period references are sufficient for achieving meaningful prognostic talk in multidisciplinary teams. In-depth discussion and accurate prediction of patient prognoses are not deemed a priority nor a necessity of these meetings. Providing precise predictions may be too difficult due to uncertainty and accountability. The lack of staff pursuing more specific time references implies shared knowledge between staff and a context-specific use of prognostic estimates.

An online international comparison of palliative care identification in primary care using the Surprise Question.

BACKGROUND: The Surprise Question ('Would I be surprised if this patient died within 12 months?') identifies patients in the last year of life. It is unclear if 'surprised' means the same for each clinician, and whether their responses are internally consistent. AIM: To determine the consistency with which the Surprise Question is used. DESIGN: A cross-sectional online study of participants located in Belgium, Germany, Italy, The Netherlands, Switzerland and UK. Participants completed 20 hypothetical patient summaries ('vignettes'). Primary outcome measure: continuous estimate of probability of death within 12 months (0% [certain survival]-100% [certain death]). A threshold (probability estimate above which Surprise Question responses were consistently 'no') and an inconsistency range (range of probability estimates where respondents vacillated between responses) were calculated. Univariable and multivariable linear regression explored differences in consistency. Trial registration: NCT03697213. SETTING/PARTICIPANTS: Registered General Practitioners (GPs). Of the 307 GPs who started the study, 250 completed 15 or more vignettes. RESULTS: Participants had a consistency threshold of 49.8% (SD 22.7) and inconsistency range of 17% (SD 22.4). Italy had a significantly higher threshold than other countries (p = 0.002). There was also a difference in threshold levels depending on age of clinician, for every yearly increase, participants had a higher threshold. There was no difference in inconsistency between countries (p = 0.53). CONCLUSIONS: There is variation between clinicians regarding the use of the Surprise Question. Over half of GPs were not internally consistent in their responses to the Surprise Question. Future research with standardised terms and real patients is warranted.

Online training improves medical students' ability to recognise when a person is dying: The ORaClES randomised controlled trial.

BACKGROUND: Recognising dying is a key clinical skill for doctors, yet there is little training. AIM: To assess the effectiveness of an online training resource designed to enhance medical students' ability to recognise dying. DESIGN: Online multicentre double-blind randomised controlled trial (NCT03360812). The training resource for the intervention group was developed from a group of expert palliative care doctors' weightings of various signs/symptoms to recognise dying. The control group received no training. SETTING/PARTICIPANTS: Participants were senior UK medical students. They reviewed 92 patient summaries and provided a probability of death within 72 hours (0% certain survival - 100% certain death) pre, post, and 2 weeks after the training. Primary outcome: (1) Mean Absolute Difference (MAD) score between participants' and the experts' scores, immediately post intervention. Secondary outcomes: (2) weight attributed to each factor, (3) learning effect and (4) level of expertise (Cochran-Weiss-Shanteau (CWS)). RESULTS: Out of 168 participants, 135 completed the trial (80%); 66 received the intervention (49%). After using the training resource, the intervention group had better agreement with the experts in their survival estimates (δMAD = -3.43, 95% CI -0.11 to -0.34, p = <0.001) and weighting of clinical factors. There was no learning effect of the MAD scores at the 2-week time point (δMAD = 1.50, 95% CI -0.87 to 3.86, p = 0.21). At the 2-week time point, the intervention group was statistically more expert in their decision-making versus controls (intervention CWS = 146.04 (SD 140.21), control CWS = 110.75 (SD 104.05); p = 0.01). CONCLUSION: The online training resource proved effective in altering the decision-making of medical students to agree more with expert decision-making.

Correction to: An online international comparison of thresholds for triggering a negative response to the "Surprise Question": a study protocol.

Following publication of the original article [1], an error in reference 18 was reported.

An online international comparison of thresholds for triggering a negative response to the "Surprise Question": a study protocol.

BACKGROUND: The Surprise Question (SQ) "would I be surprised if this patient were to die in the next 12 months?" has been suggested to help clinicians, and especially General Practitioners (GPs), identify people who might benefit from palliative care. The prognostic accuracy of this approach is unclear and little is known about how GPs use this tool in practice. Are GPs consistent, individually and as a group? Are there international differences in the use of the tool? Does including the alternative Surprise Question ("Would I be surprised if the patient were still alive after 12 months?") alter the response? What is the impact on the treatment plan in response to the SQ? This study aims to address these questions. METHODS: An online study will be completed by 600 (100 per country) registered GPs. They will be asked to review 20 hypothetical patient vignettes. For each vignette they will be asked to provide a response to the following four questions: (1) the SQ [Yes/No]; (2) the alternative SQ [Yes/No]; (3) the percentage probability of dying [0% no chance - 100% certain death]; and (4) the proposed treatment plan [multiple choice]. A "surprise threshold" for each participant will be calculated by comparing the responses to the SQ with the probability estimates of death. We will use linear regression to explore any differences in thresholds between countries and other clinician-related factors, such as years of experience. We will describe the actions taken by the clinicians and explore the differences between groups. We will also investigate the relationship between the alternative SQ and the other responses. Participants will receive a certificate of completion and the option to receive feedback on their performance. DISCUSSION: This study explores the extent to which the SQ is consistently used at an individual, group, and national level. The findings of this study will help to understand the clinical value of using the SQ in routine practice. TRIAL REGISTRATION: Clinicaltrials.gov NCT03697213 (05/10/2018). Prospectively registered.

The under reporting of recruitment strategies in research with children with life-threatening illnesses: A systematic review.

BACKGROUND: Researchers report difficulties in conducting research with children and young people with life-limiting conditions or life-threatening illnesses and their families. Recruitment is challenged by barriers including ethical, logistical and clinical considerations. AIM: To explore how children and young people (aged 0-25 years) with life-limiting conditions or life-threatening illnesses and their families were identified, invited and consented to research published in the last 5 years. DESIGN: Systematic review. DATA SOURCES: MEDLINE, PsycINFO, Web of Science, Sciences Citation Index and SCOPUS were searched for original English language research published between 2009 and 2014, recruiting children and young people with life-limiting conditions or life-threatening illness and their families. RESULTS: A total of 215 studies - 152 qualitative, 54 quantitative and 9 mixed methods - were included. Limited recruitment information but a range of strategies and difficulties were provided. The proportion of eligible participants from those screened could not be calculated in 80% of studies. Recruitment rates could not be calculated in 77%. A total of 31% of studies recruited less than 50% of eligible participants. Reasons given for non-invitation included missing clinical or contact data, or clinician judgements of participant unsuitability. Reasons for non-participation included lack of interest and participants' perceptions of potential burdens. CONCLUSION: All stages of recruitment were under reported. Transparency in reporting of participant identification, invitation and consent is needed to enable researchers to understand research implications, bias risk and to whom results apply. Research is needed to explore why consenting participants decide to take part or not and their experiences of research recruitment.

Keeping all options open: Parents' approaches to advance care planning.

BACKGROUND: Early engagement in advance care planning (ACP) is seen as fundamental for ensuring the highest standard of care for children and young people with a life-limiting condition (LLC). However, most families have little knowledge or experience of ACP. OBJECTIVE: To investigate how parents of children and young people with LLCs approach and experience ACP. METHODS: Open-ended, semi-structured interviews were conducted with parents of 18 children; nine children who were currently receiving palliative care services, and nine children who had received palliative care and died. Verbatim transcripts of audiotaped interviews were analysed following principles of grounded theory while acknowledging the use of deductive strategies, taking account of both the child's condition, and the timing and nature of decisions made. RESULTS: Parents reported having discussions and making decisions about the place of care, place of death and the limitation of treatment. Most decisions were made relatively late in the illness and by parents who wished to keep their options open. Parents reported different levels of involvement in a range of decisions; many wished to be involved in decision making but did not always feel able to do so. DISCUSSION: This study highlights that parents' approaches to decision making vary by the type of decision required. Their views may change over time, and it is important to allow them to keep their options open. We recommend that clinicians have regular discussions over the course of the illness in an effort to understand parents' approaches to particular decisions rather than to drive to closure prematurely.

Decision aids for second-line palliative chemotherapy: a randomised phase II multicentre trial.

BACKGROUND: There is increasing recognition of the delicate balance between the modest benefits of palliative chemotherapy and the burden of treatment. Decision aids (DAs) can potentially help patients with advanced cancer with these difficult treatment decisions, but providing detailed information could have an adverse impact on patients' well-being. The objective of this randomised phase II study was to evaluate the safety and efficacy of DAs for patients with advanced cancer considering second-line chemotherapy. METHODS: Patients with advanced breast or colorectal cancer considering second-line treatment were randomly assigned to usual care (control group) or usual care plus a DA (intervention group) in a 1:2 ratio. A nurse offered a DA with information on adverse events, tumour response and survival. Outcome measures included patient-reported well-being (primary outcome: anxiety) and quality of the decision-making process and the resulting choice. RESULTS: Of 128 patients randomised, 45 were assigned to the control group and 83 to the intervention group. Median age was 62 years (range 32-81), 63% were female, and 73% had colorectal cancer. The large majority of patients preferred treatment with chemotherapy (87%) and subsequently commenced treatment with chemotherapy (86%). No adverse impact on patients' well-being was found and nurses reported that consultations in which the DAs were offered went well. Being offered the DA was associated with stronger treatment preferences (3.0 vs. 2.5; p=0.030) and increased subjective knowledge (6.7 vs. 6.3; p=0.022). Objective knowledge, risk perception and perceived involvement were comparable between the groups. CONCLUSIONS: DAs containing detailed risk information on second-line palliative treatment could be delivered to patients with advanced cancer without having an adverse impact on patient well-being. Surprisingly, the DAs only marginally improved the quality of the decision-making process. The effectiveness of DAs for palliative treatment decisions needs further exploration. TRIAL REGISTRATION: Netherlands Trial Registry (NTR): NTR1113 (registered on 2 November 2007).

Patients' Preferences for Information About the Benefits and Risks of Second-Line Palliative Chemotherapy and Their Oncologist's Awareness of These Preferences.

Communication about palliative treatment options requires a balance between providing patients with sufficient information and not providing unwanted information. Surveys have indicated that many patients with advanced cancer express a wish to receive detailed information. In this prospective multicenter study, the information desire of patients with advanced breast or colorectal cancer was further investigated by offering treatment-related information to patients using a decision aid (DA). In addition, this study explored oncologists' awareness of their patients' information desire. Seventy-seven patients with advanced breast or colorectal cancer facing the decision whether to start second-line palliative chemotherapy were offered a DA by a nurse. This DA contained information on adverse events, tumor response, and survival. The nurse asked the patient whether each information item was desired. Ninety-five percent of patients chose to receive information on adverse events, 91 % chose to receive information on tumor response, and 74 % chose to receive information on survival. Oncologists' judgment of patients' information desire was 100, 97, and 81 %, respectively. For all three information items together, oncologists correctly judged the information desire of 62 % of patients. This study confirms that many patients with advanced cancer wish to receive detailed information on the benefits and risks of palliative treatment options when the information is actually available. Oncologists were adequately aware of this high information desire, but had some difficulty judging the information desire of individual patients. A stepped approach to giving information ("preview, ask, tell, ask") may help to better meet patients' information needs.

Expected survival with and without second-line palliative chemotherapy: who wants to know?

BACKGROUND: According to surveys, many patients with advanced cancer wish to receive survival information. OBJECTIVE: This study investigated information preferences by offering patients a decision aid (DA) with information on expected survival for two treatment options: supportive care with or without second-line palliative chemotherapy. Predictors of accepting survival information were explored. DESIGN: Eligible patients in this multicentre prospective study were offered second-line chemotherapy for advanced breast or colorectal cancer. A nurse presented a DA on second-line treatment and asked patients whether they desired information on (i) adverse events, (ii) tumour response and (iii) survival. Data on 50 clinical and psychosocial patient characteristics were collected from inclusion forms and patient questionnaires. RESULTS: Seventy-seven patients received a DA; median age 62 years (range 32-80), 61% female, 77% colorectal cancer. Fifty-seven patients (74%; 95% CI 64-84) desired survival information. Four psychosocial characteristics (e.g. deliberative decision style) independently predicted information desire. However, the use of these characteristics to predict information desire hardly outperformed a simple prediction rule. CONCLUSIONS: Many patients desired information on expected survival when deciding about second-line treatment. However, our exploratory analysis indicated that patients desiring this information could not be identified based on their clinical or psychosocial characteristics. These findings can help encourage candid discussions about expected survival. Health professionals should be careful not to make implicit assumptions of information desire based on patient characteristics, but to explicitly ask patients if survival information is desired, and act accordingly.

Measuring organisational readiness for patient engagement (MORE): an international online Delphi consensus study.

BACKGROUND: Widespread implementation of patient engagement by organisations and clinical teams is not a reality yet. The aim of this study is to develop a measure of organisational readiness for patient engagement designed to monitor and facilitate a healthcare organisation's willingness and ability to effectively implement patient engagement in healthcare. METHODS: The development of the MORE (Measuring Organisational Readiness for patient Engagement) scale was guided by Weiner's theory of organisational readiness for change. Weiner postulates that an organisation's readiness is determined by both the willingness and ability to implement the change (i.e. in this context: patient engagement). A first version of the scale was developed based on a literature search and evaluation of pre-existing tools. We invited multi-disciplinary stakeholders to participate in a two-round online Delphi survey. Respondents were asked to rate the importance of each proposed item, and to comment on the proposed domains and items. Second round participants received feedback from the first round and were asked to re-rate the importance of the revised, new and unchanged items, and to provide comments. RESULTS: The first version of the scale contained 51 items divided into three domains: (1) Respondents' characteristics; (2) the organisation's willingness to implement patient engagement; and (3) the organisation's ability to implement patient engagement. 131 respondents from 16 countries (health care managers, policy makers, clinicians, patients and patient representatives, researchers, and other stakeholders) completed the first survey, and 72 of them also completed the second survey. During the Delphi process, 34 items were reworded, 8 new items were added, 5 items were removed, and 18 were combined. The scale's instructions were revised. The final version of MORE totalled 38 items; 5 on stakeholders, 13 on an organisation's willingness to implement, and 20 on an organisation's ability to implement patient engagement in healthcare. CONCLUSIONS: The Delphi technique was successfully used to refine the scale's instructions, domains and items, using input from a broad range of international stakeholders, hoping that MORE can be applied in a variety of healthcare contexts worldwide. Further assessment is needed to determine the psychometric properties of the scale.

An online randomised controlled trial of prognosticating imminent death in advanced cancer patients: Clinicians give greater weight to advice from a prognostic algorithm than from another clinician with a different profession.

BACKGROUND: A second opinion or a prognostic algorithm may increase prognostic accuracy. This study assessed the level to which clinicians integrate advice perceived to be coming from another clinician or a prognostic algorithm into their prognostic estimates, and how participant characteristics and nature of advice received affect this. METHODS: An online double-blind randomised controlled trial was conducted. Palliative doctors, nurses and other types of healthcare professionals were randomised into study arms differing by perceived source of advice (algorithm or another clinician). In fact, the advice was the same in both arms (emanating from the PiPS-B14 prognostic model). Each participant reviewed five patient summaries. For each summary, participants: (1) provided an initial probability estimate of two-week survival (0% 'certain death'-100% 'certain survival'); (2) received advice (another estimate); (3) provided a final estimate. Weight of Advice (WOA) was calculated for each summary (0 '100% advice discounting' - 1 '0% discounting') and multilevel linear regression analyses were conducted. CLINICAL TRIAL REGISTRATION NUMBER: NCT04568629. RESULTS: A total of 283 clinicians were included in the analysis. Clinicians integrated advice from the algorithm more than advice from another clinician (WOA difference = -0.12 [95% CI -0.18, -0.07], p < 0.001). There was no interaction between study arm and participant profession, years of palliative care or overall experience. Advice of intermediate strength (75%) was given a lower WOA (0.31) than advice received at either the 50% (WOA 0.40) or 90% level (WOA 0.43). The overall interaction between strength of advice and study arm on WOA was significant (p < 0.001). CONCLUSION: Clinicians adjusted their prognostic estimates more when advice was perceived to come from a prognostic algorithm than from another clinician. Research is needed to understand how clinicians make prognostic decisions and how algorithms are used in clinical practice.

Efficacy and safety of palliative chemotherapy for patients with advanced breast cancer pretreated with anthracyclines and taxanes: a systematic review.

No standard monotherapy or combination palliative chemotherapy currently exists for patients with advanced breast cancer pretreated with anthracyclines and taxanes. In this systematic review we assess the current knowledge on the efficacy and safety of palliative single-agent chemotherapy drugs--capecitabine, vinorelbine, gemcitabine, and liposomal doxorubicin--commonly used in daily clinical practice. We identified 22 studies, of which ten investigated capecitabine, nine investigated vinorelbine, three investigated gemcitabine, and one investigated liposomal doxorubicin. The greatest amount of information was available for capecitabine and vinorelbine. These two drugs showed good efficacy. The disease control rate differed significantly between the four drugs, which is relevant in terms of how well tumour symptoms can be improved and whether quality of life can be maintained or even improved. To obtain more evidence of the efficacy and safety of chemotherapeutic agents used in this pretreated population of advanced breast cancer patients, randomised comparisons of the various drugs, as monotherapy and in combination with targeted agents, are needed.

Palliative care training in undergraduate medical, nursing and allied health: a survey.

OBJECTIVES: Impending death is poorly recognised. Many undergraduate healthcare professionals will not have experience of meeting or caring for someone who is dying. As death can occur in any setting, at any time, it is vital that all healthcare students, regardless of the setting they go on to work in, have end-of-life care (EOLC) training. The aim was to determine current palliative care training at the undergraduate level, in multiple professions, in recognising and communicating dying. METHODS: Current UK undergraduate courses in medicine, adult nursing, occupational therapy, social work and physiotherapy were included. All courses received an email asking what training is currently offered in the recognition and communication of dying, and what time was dedicated to this. RESULTS: A total of 73/198 (37%) courses responded to the request for information. 18/20 medical courses provided training in recognising when patients were dying (median 2 hours), and 17/20 provided training in the communication of dying (median 3 hours). 80% (43/54) of nursing and allied health professional courses provided some training in EOLC. Many of the course organisers expressed frustration at the lack of resources, funding and time to include more training. Those courses with more palliative care provision often had a 'champion' to advocate for it. CONCLUSIONS: Training in EOLC was inconsistent across courses and professions. Further research is needed to understand how to remove the barriers identified and to improve the consistency of current training.

Prognostic decision-making about imminent death within multidisciplinary teams: a scoping review.

OBJECTIVE: To summarise evidence on how multidisciplinary team (MDTs) make decisions about identification of imminently dying patients. DESIGN: Scoping review. SETTING: Any clinical setting providing care for imminently dying patients, excluding studies conducted solely in acute care settings. DATA SOURCES: The databases AMED, CINAHL, Embase, MEDLINE, PsychINFO and Web of Science were searched from inception to May 2021.Included studies presented original study data written in English and reported on the process or content of MDT discussions about identifying imminently dying adult patients. RESULTS: 40 studies were included in the review. Studies were primarily conducted using interviews and qualitative analysis of themes.MDT members involved in decision-making were usually doctors and nurses. Some decisions focused on professionals recognising that patients were dying, other decisions focused on initiating specific end-of-life care pathways or clarifying care goals. Most decisions provided evidence for a partial collaborative approach, with information-sharing being more common than joint decision-making. Issues with decision-making included disagreement between staff members and the fact that doctors were often regarded as final or sole decision-makers. CONCLUSIONS: Prognostic decision-making was often not the main focus of included studies. Based on review findings, research explicitly focusing on MDT prognostication by analysing team discussions is needed. The role of allied and other types of healthcare professionals in prognostication needs further investigation as well. A focus on specialist palliative care settings is also necessary.

Research barriers in children and young people with life-limiting conditions: a survey.

Studies indicate research ethics committee (REC) approval and clinician gatekeeping are two key barriers in recruiting children and young people (CYP) with life-limiting conditions (LLCs) and life-threatening illnesses (LTIs) and their families to research. OBJECTIVES: To explore the reported experiences, difficulties and proposed solutions of chief investigators (CIs) recruiting CYP with LLCs/LTIs and families in the UK. METHODS: 61 CIs conducting studies with CYP with LLCs/LTIs and their families, identified from the UK National Institute of Health Research portfolio, completed an anonymous, web-based questionnaire, including both closed and open-ended questions. Descriptive statistics and inductive and deductive coding were used to analyse responses. RESULTS: UK CIs cited limitations on funding, governance procedures including Research and Development, Site-Specific and REC approval processes, and clinician gatekeeping as challenges to research. CIs offered some solutions to overcome identified barriers such as working with CYP and their families to ensure their needs are adequately considered in study design and communicated to ethics committees; and designing studies with broad inclusion criteria and developing effective relationships with clinicians in order to overcome clinician gatekeeping. CONCLUSIONS: Many of the challenges and solutions reported by UK CIs have applicability beyond the UK setting. The involvement of clinicians, patients and their families at the inception of and throughout paediatric palliative care research studies is essential. Other important strategies include having clinician research champions and increasing the visibility of research. Further research on the perspectives of all stakeholders, leading to mutually agreed guidance, is required if care and treatment are to improve.

Assessing the information desire of patients with advanced cancer by providing information with a decision aid, which is evaluated in a randomized trial: a study protocol.

BACKGROUND: There is a continuing debate on the desirability of informing patients with cancer and thereby involving them in treatment decisions. On the one hand, information uptake may be hampered, and additional stress could be inflicted by involving these patients. On the other hand, even patients with advanced cancer desire information on risks and prognosis. To settle the debate, a decision aid will be developed and presented to patients with advanced disease at the point of decision making. The aid is used to assess the amount of information desired. Factors related to information desire are explored, as well as the ability of the medical oncologist to judge the patient's information desire. The effects of the information on patient well-being are assessed by comparing the decision aid group with a usual care group. METHODS/DESIGN: This study is a randomized controlled trial of patients with advanced colorectal, breast, or ovarian cancer who have started treatment with first-line palliative chemotherapy. The trial will consist of 100 patients in the decision aid group and 70 patients in the usual care group. To collect complete data of 170 patients, 246 patients will be approached for the study. Patients will complete a baseline questionnaire on sociodemographic data, well-being measures, and psychological measures, believed to predict information desire. The medical oncologist will judge the patient's information desire. After disease progression is diagnosed, the medical oncologist offers the choice between second-line palliative chemotherapy plus best supportive care (BSC) and BSC alone. Randomization will take place to determine whether patients will receive usual care (n = 70) or usual care and the decision aid (n = 100). The aid offers information about the potential risks and benefits of both treatment options, in terms of adverse events, tumour response, and survival. Patients decide for each item whether they desire the information or not. Two follow-up questionnaires will evaluate the effect of the decision aid. DISCUSSION: This study attempts to settle the debate on the desirability of informing patients with cancer. In contrast to several earlier studies, we will actually deliver information on treatment options to patients at the point of decision making.

Comparing the performance of the palliative prognostic (PaP) score with clinical predictions of survival: A systematic review.

BACKGROUND: In patients with advanced cancer, prognosis is usually determined using clinicians' predictions of survival (CPS). The palliative prognostic (PaP) score is a prognostic algorithm that was developed to predict survival in patients with advanced cancer. The score categorises patients into three risk groups in accordance with their probability of surviving for 30 days. The relative accuracy of PaP and CPS is unclear. DESIGN: This was a systematic review of MEDLINE, Embase, AMED, CINAHL Plus and the Cochrane Database of Systematic Reviews and Trials from inception up to June 2021. The inclusion criteria were studies in adults with advanced cancer reporting data on performance of both PaP and CPS. Data were extracted on accuracy of prognoses and where available on discrimination (area under the receiver operating characteristic curve or C-index) and/or diagnostic performance (sensitivity, specificity). RESULTS: Eleven studies were included. One study reported a direct comparison between PaP risk groups and equivalent risk groups defined by CPS and found that PaP was as accurate as CPS. Five studies reported discrimination of PaP as a continuous total score (rather than using the previously validated risk categories) and reported C-statistics that ranged from 0.64 (95% confidence interval [CI] 0.54, 0.74) up to 0.90 (95% CI 0.87, 0.92). Other studies compared PaP against CPS using non-equivalent metrics (e.g. comparing probability estimates against length of survival estimates). CONCLUSIONS: PaP risk categories and CPS are equally able to discriminate between patients with different survival probabilities. Total PaP scores show good discrimination between patients in accordance with their length of survival. The role of PaP in clinical practice still needs to be defined. TRIAL REGISTRATION: PROSPERO (CRD42021241074, 5th March 2021).

Systematic review of benefits and risks of second-line irinotecan monotherapy for advanced colorectal cancer.

This study was performed to obtain a comprehensive overview of the benefits and risks of second-line irinotecan monotherapy for advanced colorectal cancer. The literature was systematically reviewed to identify phase II and phase III trials that investigated the effect of second-line monotherapy with irinotecan. Thirty studies were included in this review: 25 phase II studies including 32 samples and five phase III studies including six samples. A disease control rate of greater than or equal to 50% was found in 23 out of 32 phase II samples, and one out of two phase III samples that reported disease control rate. Median time to progression was 2.7-6.0 months in phase II samples and 3.0-4.3 months in phase III samples. Median overall survival ranged from 6.6 to 16.1 months in phase II samples and 9.1-10.8 months in phase III samples. The most important severe adverse event in both phase II and phase III trials was diarrhea (5-39 and 15-36%, respectively), followed by nausea (1-24 and 5-14%), vomiting (2-22 and 6-14%), and asthenia (0-31 and 4-21%). Treatment-related mortality was 0-2% in phase II samples and 0-5% in phase III samples. Quality-of-life scores in phase II studies were associated with tumor response. In phase III studies, the quality of life while on treatment with irinotecan was similar to that of 5-fluorouracil, but better than supportive care alone. The quality of life on the weekly schedule was similar to the 3-weekly schedule. This study provides a comprehensive overview of the benefits and risks of second-line irinotecan. In general, second-line treatment with irinotecan is beneficial to patients.