Advanced Cancer Population Research Articles

Assessing the credibility and transferability of the patient compassion model in non-cancer palliative populations

BackgroundA lack of evidence and psychometrically sound measures of compassion necessitated the development of the first known, empirically derived, theoretical Patient Compassion Model (PCM) generated from qualitative interviews with advanced cancer inpatients. We aimed to assess the credibility and transferability of the PCM across diverse palliative populations and settings.MethodsSemi-structured, audio-recorded qualitative interviews were conducted with 20 patients with life-limiting diagnoses, recruited from 4 settings (acute care, homecare, residential care, and hospice). Participants were first asked to share their understandings and experiences of compassion. They were then presented with an overview of the PCM and asked to determine whether: 1) the model resonated with their understanding and experiences of compassion; 2) the model required any modification(s); 3) they had further insights on the model’s domains and/or themes. Members of the research team analyzed the qualitative data using constant comparative analysis.ResultsBoth patients’ personal perspectives of compassion prior to viewing the model and their specific feedback after being provided an overview of the model confirmed the credibility and transferability of the PCM. While new codes were incorporated into the original coding schema, no new domains or themes emerged from this study sample. These additional codes provided a more comprehensive understanding of the nuances within the domains and themes of the PCM that will aid in the generation of items for an ongoing study to develop a patient reported measure of compassion.ConclusionsA diverse palliative patient population confirmed the credibility and transferability of the PCM within palliative care, extending the rigour and applicability of the PCM that was originally developed within an advanced cancer population. The views of a diverse palliative patient population on compassion helped to validate previous codes and supplement the existing coding schema, informing the development of a guiding framework for the generation of a patient-reported measure of compassion.

Outcomes of a Dignity Therapy/Life Plan Intervention for Patients With Advanced Cancer Undergoing Chemotherapy.

Dignity therapy is a psychosocial intervention provided at the end of life to improve patient outcomes, but many persons cannot complete it because of health decline. Patients also reprioritize their life plans as death becomes imminent. As part of meeting standards to provide psychosocial palliative care simultaneously with cancer treatment, we provided a dignity therapy/life plan intervention to 18 patients with advanced pancreatic or lung cancer receiving cancer treatment. The study aim was to evaluate patient-reported outcomes of dignity therapy/life plan. Dignity therapy entailed interviews during 3 outpatient oncology encounters, which then became a legacy document for family. Participants documented life goals as their life plan. Distress, quality of life, spirituality, dignity, and purpose in life were measured at baseline, immediately after intervention, and 3 months later. No variables were significantly different from baseline to postintervention and 3 months later, except for less distress between baseline and 3 months (P = .04). Although this intervention did not show improvements in outcomes, patients with advanced disease receiving active treatment typically experience worsening symptoms overall. Maintaining psychosocial outcomes may be preventing further morbidity in an advanced cancer population during treatment and bears further exploration. Given our small sample size, further research is warranted.

Treatment in the STAMPEDE era for castrate resistant prostate cancer in the UK: ongoing challenges and underappreciated clinical problems

BackgroundThis study aimed to explore the opinions of healthcare professionals regarding the management of men with advanced prostate cancer with particular emphasis on treatment timing and sequencing; treatment adverse-effects and exercise a supportive therapy.MethodsSemi-structured interviews with a purposively selected group of healthcare professionals involved in prostate cancer care within the NHS, conducted over the phone or face to face. A total of 37 healthcare professionals participated in the interviews including urologists, clinical oncologists, medical oncologists, clinical nurse specialists, general practitioners, physiotherapists, exercise specialists, service managers, clinical commissioners and primary care physicians.ResultsThe availability of newer treatments for advanced prostate cancer as well as results from the STAMPEDE and CHAARTED trials has resulted in new challenges for patients and HCPs. This includes the impact of an increased workload on oncologists, a potential lack of clinical continuity between urology and oncology and uncertainties regarding optimal selection, timing and sequencing of chemotherapy and second-line treatment. Fitness for treatment in advanced prostate cancer populations remains a significant barrier to accessing therapies for patients with a poor performance status. Among this, muscle wastage can significantly affect performance status and consequentially compromise cancer therapy. Exercise was regarded as a potential therapy to mitigate the adverse-effects of treatment including the prevention or reduction in muscle wastage.ConclusionsThere is a lack of data guiding clinicians in this post STAMPEDE and CHAARTED era, work is needed to reassess and optimize the prostate cancer care pathway as it evolves. Exercise should be explored as a therapeutic option to mitigate the effects of long term ADT. Further study from a wider cohort of both prostate cancer care specialists and patients will aid in establishing a highly functioning pathway with optimal individualised care.Trial registrationSustained exercise TrAining for Men wIth prostate caNcer on Androgen deprivation: the STAMINA programme (RP-DG-1213-10,010). REC Reference: 15/SW/0260 IRAS Project ID: 178340 Hospital ID: STH 18391 approved on 24/08/2015.

(211) - Analysis of the analgesic therapeutic profile needed to achieve an optimal pain control in a sample of advanced cancer population: Experience from an out-patient clinic in a catalan teaching hospital

(211) - Analysis of the analgesic therapeutic profile needed to achieve an optimal pain control in a sample of advanced cancer population: Experience from an out-patient clinic in a catalan teaching hospital

Implementing the Bereaved Family Survey for an Advanced Cancer Population (QI805)

Implementing the Bereaved Family Survey for an Advanced Cancer Population (QI805)

Utilization of Support Services, Emergency Department and Hospitalization in Advanced Cancer Patients with Severe Disease in a Community Cancer Institute (QI809)

•Define advanced cancer population and severity of disease.•Describe a model of support service delivery in a community cancer institute.•State the correlation of as-needed support service referral on ED utilization and unplanned hospitalizations in one community cancer center. Patients with advanced cancer are at high risk for emergency department (ED) and hospital utilization, which is distressing and costly. Palliative care consultation and symptom management clinics have been shown to decrease ED and hospital utilization, but the frequency and composition of these interventions is still being delineated. To describe healthcare utilization in patients with advanced cancer with respect to support services provided and severity of disease in a community setting. 157 patients with advanced cancer of pulmonary, gastrointestinal, genitourinary or gynecologic origin diagnosed January-December 2015 were reviewed retrospectively. Descriptive data including demographics, disease characteristics, palliative care consultation, support services utilized, and ED visits/hospitalizations were collected for 12 months, or to date of death. Support services included physician assistant–led symptom management, nurse navigator, social worker, nutrition, financial counselor, chaplain, and oncology clinical counselor. Support service referrals were made based on identified needs. Severe disease was defined as death within 6 months of diagnosis. Patients with severe disease had a mean of 6 ED visits per year, significantly greater than patients with non-severe disease (p < 0.001). Patients with severe disease also had more contacts with support services per year (30.3 vs 9.1, p < 0.001). A palliative care consult was placed in 50% of patients with severe disease, and 23% in patients with non-severe disease (p < 0.001). Patients with advanced cancer have high healthcare utilization in the last 6 months of life. As-needed involvement of support services correlated with severity of disease but did not result in decreased ED utilization or hospitalization. These data suggest that availability of as-needed support services alone is not a reliable strategy to impact unplanned hospitalizations and ED visits. Further research is needed to determine if preemptive or mandatory utilization of support services is sufficient to reduce healthcare utilization.

Outcomes of a Dignity Therapy/Life Plan intervention for advanced cancer patients undergoing treatment.

177 Background: Dignity Therapy (DT) is a psychosocial intervention used primarily at the end of life to improve quality of life and promote patient dignity, but many individuals are unable to complete it due to health decline/death. In addition, when individuals face potential mortality, they evaluate life plans to determine tasks and behaviors most important to them. Consistent with guidelines to provide palliative care interventions simultaneously with cancer treatment, the purpose of this study was to evaluate initial patient-reported outcomes of an intervention combination (Dignity Therapy + Life Plan [DT/LP]) for those with advanced pancreatic or lung cancer receiving treatment within a year of diagnosis. Methods: This was a single-arm, Phase I/II pilot study, conducted in the outpatient setting at an NCI-designated comprehensive cancer center. Dignity Therapy consisted of a focused life review intervention delivered during three outpatient oncology encounters for each patient. Interviews were audiotaped, transcribed, and edited to produce a legacy document. Participants scribed a list of 3-6 life goals for the LP intervention. Outcomes measured at baseline, immediately post DT/LP, and 3 months later were distress (Distress Thermometer), quality of life (FACT and LASA), spirituality (FaCIT-Sp-12), dignity (Patient Dignity Inventory), and purpose in life (Purpose in Life Test- Short Form). Data were analyzed with one-sample, two-sided t-tests (alternate: Wilcoxan). Results: Eighteen advanced pancreatic or lung cancer patients enrolled, mean age 64. There were no significant differences among all variables from baseline to post-DT/LP and 3 months later, with the exception of less distress experienced between baseline and 3 months after DT/LP ( p= 0.04). Conclusions: The DT/LP intervention did not show improvements in these psychosocial outcomes, but patients with advanced cancer typically experience worsening physical and psychosocial symptoms with active treatment. Therefore, maintaining these outcomes from baseline is a worthy goal, as we may be preventing further morbidity in an advanced cancer population. Further research is needed, however, given this small sample size. Clinical trial information: NCT02132325.

Implementing the Bereaved Family Survey for an advanced cancer population.

76 Background: Despite being endorsed as a National Quality Forum measure, the Bereaved Family Survey (BFS), a tool to assess a patient’s end-of-life (EOL) experience, has not been broadly used outside the Veteran’s Affairs Health System or in the outpatient setting. We adapted the BFS for an advanced cancer population and implemented it at an academic health system to identify areas for quality improvement in EOL care. Methods: Between August 2016 and May 2017, we surveyed caregivers of advanced cancer decedents. We included English-speaking decedents &gt; 18 years of age who were continuity patients of a health system oncologist and had documentation of metastatic disease in either problem list, oncology notes, or advanced imaging. Death was verified in the chart or by obituary found via internet search. Caregivers surveyed were the appointed healthcare agent in an advance directive or the first listed contact. Scoring was done via the top-box approach. Surveys were mailed 3 months after death with a follow-up post-card reminder and phone-call at 2 and 4 weeks, respectively. Results: Of 285 eligible decedents, 242 caregivers were mailed surveys with 83 completed (34% response rate) of whom 28% died in the hospital. Mean overall BFS score was 75 out of 100. Ratings were high for overall care quality (78% Always/Usually) and staff caring (74% Always) with lower ratings for communication (58% Always), emotional/spiritual support (37% Always with 30% not wanting support) and pain control (56% Always/Usually uncomfortable). Nearly 84% of respondents felt their loved one died in the right place and 67% felt staff caring for the patient provided a dignified death. 74% of patients were referred to hospice with 64% of caregivers stating the hospice referral was timely. Write-in responses mentioned concerns about caregiver support, the quality and timeliness of hospice care and communication between physician and patient/caregiver. Over half of statements were positive remarks about a physician or ancillary staff member. Conclusions: A post-mortem survey implemented for an advanced cancer population received a modest response rate but collected valuable information regarding gaps in care quality to drive quality improvement.

The ExPeCT (Examining Exercise, Prostate Cancer and Circulating Tumour Cells) trial: study protocol for a randomised controlled trial

BackgroundProstate cancer (PrCa) is the second most common cancer in Ireland. Many men present with locally advanced or metastatic cancer for whom curative surgery is inappropriate. Advanced cancer patients are encouraged to remain physically active and therefore there is a need to investigate how patients with metastatic disease tolerate physical activity programmes. Physical activity reduces levels of systemic inflammatory mediators and so an aerobic exercise intervention may represent an accessible and cost-effective means of ameliorating the pro-inflammatory effects of obesity and subsequently decrease poor cancer-specific outcomes in this patient population. This study will assess the feasibility and safety of introducing a structured aerobic exercise intervention to an advanced cancer population. This study will also examine if the evasion of immune editing by circulating tumour cells (CTCs) is an exercise-modifiable mechanism in obese men with prostate cancer.MethodsThis international multicentre prospective study will recruit men with metastatic prostate cancer. Participants will be recruited from centres in Dublin (Ireland) and London (UK). Participants will be divided into exposed and non-exposed groups based on body mass index (BMI) ≥ 25 kg/m2 and randomised to intervention and control groups. The exercise group will undertake a regular supervised aerobic exercise programme, whereas the control group will not. Exercise intensity will be prescribed based on a target heart rate monitored by a polar heart rate monitor. Blood samples will be taken at recruitment and at 3 and 6 months to examine the primary endpoint of platelet cloaking of CTCs. Participants will complete a detailed questionnaire to assess quality of life (QoL) and other parameters at each visit.DiscussionThe overall aim of the ExPeCT trial is to examine the relationship between PrCa, exercise, obesity, and systemic inflammation, and to improve the overall QoL in men with advanced disease. Results will inform future work in this area examining biological markers of prognosis in advanced prostate cancer.Trial registrationClinicaltrials.gov NLM identifier: NCT02453139. Registered on 12 May 2015. This document contains excerpts from the ExPeCT trial protocol Version 1.5, 28 July 2016.

Safety and feasibility of exercise interventions in patients with advanced cancer: a systematic review.

The beneficial effects of exercise in cancer patients are reasonably well-established, although research in this field has predominantly investigated cancer patients in the earlier stages of disease. However, the most recent evidence surrounding exercise interventions in advanced cancer populations has yet to be systematically evaluated. This review critically analyses the safety and feasibility of exercise interventions in patients with advanced cancer. All randomised, non-randomised and prospective observational trials of exercise training interventions in patients with advanced cancer were included. 'Safety' was defined as the number and severity of reported adverse events during exercise training. 'Feasibility' was determined by participant adherence, attendance and/or study completion rates. A total of 25 studies involving 1088 patients were included: 16 randomised controlled and nine prospective observational cohort trials. Seven studies included advanced lung cancer patients exclusively, while eight involved patients with various cancer diagnoses. Aerobic exercise was investigated in five studies, resistance training in two studies and combination training (aerobic and resistance) in 14 studies. Six minor adverse events were reported due to exercise. All of these were musculoskeletal in nature, resulting in two participants' withdrawal from the study. Exercise adherence ranged from 65 to 89% but was only described in nine studies. Attendance at each exercise session was described in a further nine studies, ranging from 59 to 100%. Implementation of exercise interventions appears to be safe and feasible in advanced cancer clinical practice, although targeted studies are required to determine the optimal exercise dose for specific cancer diagnoses.

Exercise interventions for individuals with advanced cancer: A systematic review.

Despite improvements in therapy a large proportion of individuals with cancer will have a shortened life expectancy because of advanced or metastatic disease. Advances in therapy have however, extended life in those with advanced cancer thus heightening the importance of living well and preventing decline. The burdens of disease and cancer therapy impair aerobic fitness, strength, physical function and quality of life (QOL). Fatigue, the most common side effect of cancer and cancer therapy can further deteriorate QOL. Exercise has the potential to improve aerobic fitness, physical function, control fatigue and enhance QOL. However, exercise interventions are not routinely provided to those with advanced cancer. We present a systematic literature review of outcomes from interventions that include exercise for patients with advanced cancer. Studies were reviewed if they included an advanced cancer population and an intervention with a component of exercise. Overall, exercise containing interventions resulted in improvements in measures of aerobic capacity (14 of 19 studies) strength (11 of 12 studies), and components of physical function (9 of 9 studies). Fatigue and QOL were identified to improve in slightly over half of all evaluated studies (11 of 19 studies and 10 of 19 studies for fatigue and QOL respectively). The numbers of total participants reporting improvements in QOL (60%) were greater than fatigue (45%). Exercise provided to individuals with advanced cancer maintains or improves fitness and physical function and may diminish fatigue and enhance QOL and should be considered as an intervention to prevent further health complications.

P1.03-019 Imaging of Anti-PD1 Therapy Response in Advanced Non-Small Lung Cancer

Therapy with immune checkpoint inhibitors can lead to unconventional tumor responses and autoimmune-mediated adverse effects resulting from immune activation. Here we sought to determine pseudo-progression and radiologically-evident anti-PD1 therapy mediated adverse events in routine clinical management in the advanced non-small cell lung cancer (NSCLC) population. A retrospective study was conducted of all adult NSCLC patients treated with anti-PD1 agents at our institution. Electronic medical records were reviewed to determine clinical assessment of anti-PD1 therapy response and imaging reports at restaging. Patients that did not have available follow-up imaging or clinical data while on anti-PD1-therapy were excluded from the study. Patient imaging exams with clinically suspected tumor pseudo-progression at 1st re-staging were analyzed to determine if subsequent imaging demonstrated pseudo-progression or true progression. The incidence of radiographically-evident adverse events attributed to anti-PD1 therapy by the oncologist were noted. A total of 228 patients were started on anti-PD1 therapy at our institution, of which a total of 166 were evaluable. Of the evaluable patients, 80% of those received nivolumab and the remaining 20% received pembrolizumab. The overall response rate (complete response + partial response) was 23% at 1st restaging. Of these patients, 22 patients were suspected of pseudo-progression due to tumor enlargement and/or development of new lesions during the 1st 4-6 weeks of therapy and were maintained on anti-PD1 therapy. Of these patients, there were 5 confirmed cases of pseudo-progression at subsequent restaging. Radiologically-evident adverse events occurred in less than 5% of the population, primarily manifesting as pneumonitis. Pseudo-progression and radiographically-evident adverse events are important but uncommon occurrences in the setting of anti-PD1 therapy for advanced NSCLC.

(123) Non-adherence to strong opioids regime in an advanced cancer population with pain: pharmacological pitfalls, or not

(123) Non-adherence to strong opioids regime in an advanced cancer population with pain: pharmacological pitfalls, or not

Pilot Evaluation of Auricular Acupressure in End-Stage Lung Cancer Patients.

Dyspnea is a common symptom in end-stage lung cancer patients and is only infrequently controlled. Currently, the use of complimentary therapies using traditional Chinese medicine (TCM), including auricular application of Vaccaria segetalis (a small seed), is understudied. Acupressure using auricular Vaccaria segetalis application has been reported as effective in reducing dyspnea when applied to a specific area of the ear associated with lung function in the TCM paradigm. The purpose of this feasibility study was to evaluate the effects of standardized auricular acupressure therapy using Vaccaria segetalis on dyspnea intensity and distress and oxygen saturation in end-stage lung cancer patients. The experimental design was three conditions with eight measurement points in time. Patients were randomly assigned to one of three treatment conditions: (1) Standard Care (SC); (2) SC with Vaccaria segetalis taped to random auricular locations (placebo); and (3) SC with Vaccaria segetalis taped to the auricular location deemed specific to lung function in TCM. Subjects were 11 hospice patients with advanced lung cancer and dyspnea. Dyspnea intensity and distress were measured by the Cancer Dyspnea Scale (CDS) and oxygen saturation was measured by pulse oximeter at eight time points. Non-parametric statistical analyses suggest the presence of acupressure effects with medium to large effects and significant effect for dyspnea effort. This pilot information suggests the need for further study of auricular acupressure using Vaccaria segetalis in the dyspneic advanced lung cancer population.

Role of methylphenidate in the treatment of fatigue in advanced pancreatic cancer population.

BackgroundFatigue is a common but devastating symptom for advanced pancreatic cancer (APC) patients. To date, no proven treatment exists. Methylphenidate (MPH) showed inconsistent results in treating other cancer related fatigue. We performed a retrospective study to assess MPH in ameliorating fatigue in APC patients.MethodsWe retrospectively reviewed our clinic APC patients’ records who visited from 06/2011 - 11/2014. Fatigue was assessed by Visual Analog Fatigue Scale (VAFS) and classified as grade 1 (VAFS 1-3), grade 2 (VAFS 4-6) and grade 3 (VAFS 7-10) to correspond with CTCAE V4.0. MPH was dosed at 5 mg daily in the morning and was escalated to 10 mg after 2 weeks if needed. The primary endpoint was to assess the change of fatigue grade after 4 weeks of MPH. Secondary outcomes included MPH’s effect on depression, anorexia, maintenance chemotherapy intensity and adverse effects.ResultsA total of 71 APC patients on concomitant chemotherapy were included, of whom 67% received doublet, 13% triplet, and 20% single-agent chemotherapy. Mean baseline VAFS was 7, which dropped to 4 after 4 weeks of MPH, 55% patients’ fatigue score improved by 1 grade, 8% by 2 grades, 23% had fatigue resolved, 14% without benefit. 72% patients maintained chemotherapy intensity, 39% felt less depression and 52% had improved appetite. 13% stopped MPH due to side effects. Rare Grade 3 or 4 adverse events included insomnia, restlessness, palpitations and anorexia.ConclusionsOur findings support low-dose MPH benefits APC patients with improved fatigue, depression and anorexia. A large randomized clinical trial is needed to confirm its usage and safety.

Palliative Pharmacotherapy: State-of-the-Art Management of Symptoms in Patients With Cancer.

Advanced cancer produces multiple symptoms as patients progress through their disease trajectory. Identifying, measuring, and providing therapy for uncontrolled symptoms becomes important because disease-altering therapies may be no longer possible. Symptoms other than pain that cause distress in patients with cancer include delirium, dyspnea, anorexia, nausea, and fatigue. Precise management of these symptoms can lead to the best possible quality of life and lessen distress. This article reviews current management strategies of these symptoms. The epidemiology, mechanisms, assessment, and therapies of common symptoms in the advanced cancer population are reviewed. Identifiable approaches facilitate symptom management in advanced illness. Using a systematic approach to symptoms in advanced illness can improve the quality of life and lessen distress among patients with cancer and their families, friends, and caregivers.

Validation and real-world assessment of the Functional Assessment of Anorexia-Cachexia Therapy (FAACT) scale in patients with advanced non-small cell lung cancer and the cancer anorexia-cachexia syndrome (CACS).

Patients with cancer anorexia-cachexia syndrome (CACS) suffer a significant symptom burden, impaired quality of life (QoL), and shorter survival. Measurement of QoL impairments related to CACS is thereby important both in clinical practice and in research. We aimed to further validate the Functional Assessment of Anorexia-Cachexia Therapy (FAACT) scale in an advanced lung cancer population. We tested the performance of the FAACT and its anorexia-cachexia subscale (ACS) within a dataset of patients with advanced non-small cell lung cancer (aNSCLC), using standard statistical methods. We then compared the performance of commonly used QoL measures stratified by CACS status and by patient self-report of appetite and weight loss. The FAACT and its ACS demonstrate internal validity consistent with acceptable published ranges for other QoL scales (Cronbach alpha = 0.9 and 0.79, respectively). Correlation coefficients demonstrate moderate correlations in the expected directions between FAACT and ACS and scales that measure related constructs. Comparing patients with and without CACS, the ACS is more sensitive to change than other QoL instruments (mean score 33.1 vs. 37.2, p = 0.011, ES = 0.58). In patients with aNSCLC, the FAACT and its ACS performed well compared with other instruments, further supporting their validity and value in clinical research. FAACT and ACS scores covaried with symptoms and other QoL changes that are typical hallmarks of CACS, lending further support to their use as QoL endpoints in clinical trials among patients with CACS.

PROMs from hospital to hospice.

209 Background: Symptom burden in advanced cancer patients (pts) influences quality of life (QoL) and should be leading in advanced care planning for both hospital and hospice populations. The objective is to describe the course of symptomburden in those patients over time. Methods: Symptoms were biweekly assessed with the self-assessment tool Edmonton Symptom Assessment System (ESAS; Dutch translation) in a prospective longitudinal study of hospitalized patients and patients admitted to a hospice. Prevalence and intensity data were entered in a web-based database by distinguishing patients into 3 groups regarding the aim of palliative care: tumor palliation, symptom palliation and terminal care. Results: 808 pts included, mean age 65 (18-93), 57% female; 224 (30%) pts admitted in the hospice-setting, 584 (70%) in a medical oncology ward. The care aimed 36 % tumor palliation, 59% symptom management, 4% terminal care. Most prevalent symptoms were similar in hospital and hospice: fatigue, anorexia, dry mouth, pain, constipation. The highest clinical relevance (score &gt; 4 on NRS 0-10; 0 = no symptom, 10 = worst symptom) was found in hospital for fatigue (56%), anorexia (54%), constipation (48%), dry mouth (44%), pain (33%). In hospice patients fatigue (88%), dry mouth (66%), anorexia (63%), pain (4%), constipation (40%). In both care settings same national guidelines for symptom management are used as bottom line for interventions. 48% hospital patients scored &gt; 4 for overall wellbeing (0= very good, 10 = very bad) vs 68% in hospice. In the hospice cohort pts are discriminated by prognosis, symptomburden, QoL: &gt; 3 months survival, 2 – 12 weeks, &lt; 2 weeks. Analysis is ongoing, data will be presented at the conference. Conclusions: The course of symptom intensity in advanced cancer populations in hospital and hospice setting is quite similar. A combination of general, specialized and expert palliative care competencies are needed during the cancer continuum. Prospective monitoring of patients during the continuum is a methodological and practical challenge.

Population pharmacokinetics and exposure–response analyses of trastuzumab in patients with advanced gastric or gastroesophageal junction cancer

The aim of this study was to characterize trastuzumab population pharmacokinetics (PKs) in patients with human epidermal growth factor receptor 2-positive advanced gastric or gastroesophageal junction cancer and the relationship of trastuzumab PK with patient response. A nonlinear mixed effects PK model was built using data from the ToGA study. Patients were randomized to intravenous trastuzumab plus chemotherapy or chemotherapy alone. The influence of demographic, laboratory, and disease characteristics on PK parameters was assessed. An exploratory exposure-response analysis compared various PK parameters at steady state with best overall tumor response and overall survival (OS). Trastuzumab PK was best described by a two-compartment model with parallel linear and nonlinear (Michaelis-Menten) elimination from the central compartment. Total clearance (and half-life) of trastuzumab was concentration-dependent. Body weight, prior gastrectomy, and serum albumin had the greatest influence on trastuzumab PK; increasing weight and decreasing albumin levels were associated with increased clearance, while prior gastrectomy correlated with decreased clearance. Median values for AUC, Cmax, and Cmin were lower in patients with progressive disease (PD) than other response categories, although the 1.5 interquartile ranges overlapped. Patients with the lowest Cmin had the highest PD rate and a shorter OS. In the advanced gastric cancer population, trastuzumab PK was best described by a two-compartment model with parallel linear and nonlinear elimination. Predicted PK exposure was lower than previously reported for breast cancer. Patients with the lowest Cmin had a shorter OS and the highest PD rate, but a distinct correlation was not observed for tumor response.

Complementary and alternative medicine (CAM) use in advanced cancer: a systematic review

This systematic review synthesizes knowledge about the use of complementary and alternative medicine (CAM) among advanced cancer patients. EBSCO and Ovid databases were searched using core concepts, including advanced cancer, CAM, integrative medicine, and decision-making. Articles included in the final review were analyzed using narrative synthesis methods, including thematic analysis, concept mapping, and critical reflection on the synthesis process. Results demonstrate that advanced cancer patients who are younger, female, more educated, have longer duration of disease, and have previously used CAM are more likely to use CAM during this stage of illness. Key themes identified include patterns of and reasons for use; and barriers and facilitators to informed CAM decision-making. Knowledge regarding the use of CAM in advanced cancer remains in its nascent stages. Findings suggest a need for more research on understanding the dynamic process of CAM decision-making in the advanced cancer population from the patients' perspective.