NCCN Guidelines® Insights: Palliative Care, Version 2.2021.

Palliative care has evolved to be an integral part of comprehensive cancer care with the goal of early intervention to improve quality of life and patient outcomes. The NCCN Guidelines for Palliative Care provide recommendations to help the primary oncology team promote the best quality of life possible throughout the illness trajectory for each patient with cancer. The NCCN Palliative Care Panel meets annually to evaluate and update recommendations based on panel members' clinical expertise and emerging scientific data. These NCCN Guidelines Insights summarize the panel's recent discussions and highlights updates on the importance of fostering adaptive coping strategies for patients and families, and on the role of pharmacologic and nonpharmacologic interventions to optimize symptom management.

Barriers to Goal-concordant Care for Older Patients With Acute Surgical Illness: Communication Patterns Extrinsic to Decision Aids.

OBJECTIVE: We sought to characterize patterns of communication extrinsic to a decision aid that may impede goal-concordant care. BACKGROUND: Decision aids are designed to facilitate difficult clinical decisions by providing better treatment information. However, these interventions may not be sufficient to effectively reveal patient values and promote preference-aligned decisions for seriously ill, older adults. METHODS: We conducted a secondary analysis of 31 decision-making conversations between surgeons and frail, older inpatients with acute surgical problems at a single tertiary care hospital. Conversations occurred before and after surgeons were trained to use a decision aid. We used directed qualitative content analysis to characterize patterns within 3 communication elements: disclosure of prognosis, elicitation of patient preferences, and integration of preferences into a treatment recommendation. RESULTS: First, surgeons missed an opportunity to break bad news. By focusing on the acute surgical problem and need to make a treatment decision, surgeons failed to expose the life-limiting nature of the patient's illness. Second, surgeons asked patients to express preference for a specific treatment without gaining knowledge about the patient's priorities or exploring how patients might value specific health states or disabilities. Third, many surgeons struggled to integrate patients' goals and values to make a treatment recommendation. Instead, they presented options and noted, "It's your decision." CONCLUSIONS: A decision aid alone may be insufficient to facilitate a decision that is truly shared. Attention to elements beyond provision of treatment information has the potential to improve communication and promote goal-concordant care for seriously ill older patients.

Assessment of adherence and relative dose intensity with oral chemotherapy in oncology clinical trials at an academic medical center.

Background/Aims Oral chemotherapy is increasingly utilized leaving the patient responsible for self-administering an often complex regimen where adverse effects are common. Non-adherence and reduced relative dose intensity are both associated with poorer outcomes in the community setting but are rarely reported in clinical trials. The purpose of this study is to quantify adherence and relative dose intensity in oncology clinical trials and to determine patient and study related factors that influence adherence and relative dose intensity. Methods Patients were identified from non-industry-funded clinical trials conducted between 1 January 2009 and 31 March 2013 at the University of Wisconsin Carbone Cancer Center. Data were extracted from primary research records. Descriptive statistics and linear regression modeling was performed using SAS 9.4. Results A total of 17 clinical trials and 266 subjects were included. Mean adherence was greater than 97% for the first eight cycles. Mean relative dose intensity was less than 90% for the first cycle and declined over time. Male gender, a performance status of 1 or 2, metastatic disease, and traveling more than 90 miles to reach the cancer center were associated with higher relative dose intensity. Conclusions Patients with cancer enrolled in clinical trials are highly adherent but unlikely to achieve protocol specified relative dose intensity. Given that determining the phase II dose is the primary endpoint of phase I trials, incorporating relative dose intensity into this determination should be considered.

The Utilization of Palliative Care Services in Patients with Cirrhosis who have been Denied Liver Transplantation: A Single Center Retrospective Review.

INTRODUCTION AND AIM: Utilization of palliative care services in patients dying of end-stage liver disease (ESLD) is understudied. We performed a retrospective review of palliative care services among patients with ESLD unsuitable for liver transplantation (LT) at a tertiary care center. MATERIAL AND METHODS: Deceased ESLD patients considered unsuitable for LT from 2007-2012 were identified. Patients were excluded if they received a transplant, had an incomplete workup, were lost to follow up or whose condition improved so LT was not needed. Of the 1,175 patients reviewed, 116 met inclusion criteria. RESULTS: Forty patients (34.4%) received an inpatient palliative care (PC) consultation and forty-one patients (35.3%) were referred directly to hospice. Thirty-three patients (28.4%) transitioned to comfort measures without PC consultation (median survival < 1 day). The median interval between LT denial and PC consultation or hospice was 28 days. Median survival after PC consult or hospice referral was 15 days. In conclusion, in a single center retrospective review of ESLD patients, palliative care services, when utilized, were for care at the very end of life. Without consultation, aggressive interventions continued until hours before death. We propose that ESLD patients could benefit from PC consultation at time of LT evaluation or based on MELD scores.

Constructing High-stakes Surgical Decisions: It's Better to Die Trying.

OBJECTIVE: To explore high-stakes surgical decision making from the perspective of seniors and surgeons. BACKGROUND: A majority of older chronically ill patients would decline a low-risk procedure if the outcome was severe functional impairment. However, 25% of Medicare beneficiaries have surgery in their last 3 months of life, which may be inconsistent with their preferences. How patients make decisions to have surgery may contribute to this problem of unwanted care. METHODS: We convened 4 focus groups at senior centers and 2 groups of surgeons in Madison and Milwaukee, Wisconsin, where we showed a video about a decision regarding a choice between surgery and palliative care. We used qualitative content analysis to identify themes about communication and explanatory models for end-of-life treatment decisions. RESULTS: Seniors (n = 37) and surgeons (n = 17) agreed that maximizing quality of life should guide treatment decisions for older patients. However, when faced with an acute choice between surgery and palliative care, seniors viewed this either as a choice between life and death or a decision about how to die. Although surgeons agreed that very frail patients should not have surgery, they held conflicting views about presenting treatment options. CONCLUSIONS: Seniors and surgeons highly value quality of life, but this notion is difficult to incorporate in acute surgical decisions. Some seniors use these values to consider a choice between surgery and palliative care, whereas others view this as a simple choice between life and death. Surgeons acknowledge challenges framing decisions and describe a clinical momentum that promotes surgical intervention.

Statin use in cancer patients with brain metastases: a missed communication opportunity at the end of life.

PURPOSE: Preventive care, referring to medical interventions with anticipated long-term benefits, is often inappropriately continued near the end of life. We examined the use of statin medications in patients with brain metastases receiving whole brain radiation therapy to determine the effect of short life expectancy and regular interaction with oncology providers on statin discontinuation. We propose reasons for the unnecessary continuation of preventive care and suggest that it is a frequently missed communication opportunity to discuss prognosis in a concrete manner. METHODS: This is a retrospective study examining statin use in patients receiving whole brain radiotherapy for brain metastases. A total of 206 patients at two cancer centers were studied, and information on statin use and clinical characteristics was obtained from review of the medical record. RESULTS: Of the 206 patients, 53 (26 %) were on a statin at their initial radiation oncology consultation. Of these patients, 13 (25 %) had their statin discontinued by the time of their last follow-up visit, but 40 patients (75 %) were continued on their statin despite their limited life expectancy and low likelihood of benefit. CONCLUSIONS: The majority of patients who were on statins prior to starting palliative whole brain radiation therapy remained on a statin after completing treatment despite an estimated survival of months and regular visits with an oncologist. This represents a missed opportunity for doctors and patients to discuss the appropriateness of continuing preventive care as part of an important conversation about prognosis.

Vorinostat and bortezomib as third-line therapy in patients with advanced non-small cell lung cancer: a Wisconsin Oncology Network Phase II study.

INTRODUCTION: The primary objective of this phase II trial was to evaluate the efficacy and tolerability of vorinostat and bortezomib as third-line therapy in advanced non-small cell lung cancer (NSCLC) patients. METHODS: Eligibility criteria included recurrent/metastatic NSCLC, having received 2 prior systemic regimens, and performance status 0-2. Patients took vorinostat 400 mg PO daily days 1-14 and bortezomib 1.3 mg/m2 IV day 1, 4, 8 and 11 in a 21-day cycle. Primary endpoint was 3-month progression free survival (3m-PFS), with a goal of at least 40 % of patients being free of progression at that time point. This study followed a two-stage minimax design. RESULTS: Eighteen patients were enrolled in the first stage. All patients had two prior lines of treatment. Patients received a median of two treatment cycles (range: 1-6) on study. There were no anti-tumor responses; stable disease was observed in 5 patients (27.8 %). Median PFS was 1.5 months, 3m-PFS rate 11.1 %, and median overall survival 4.7 months. The most common grade 3/4 toxicities were thrombocytopenia and fatigue. Two patients who had baseline taxane-related grade 1 peripheral neuropathy developed grade 3 neuropathy. The study was closed at its first interim analysis for lack of efficacy. CONCLUSIONS: Bortezomib and vorinostat displayed minimal anti-tumor activity as third-line therapy in NSCLC. We do not recommend this regimen for further investigation in unselected patients.

Beyond Chemoimmunotherapy in Advanced Non-Small Cell Lung Cancer: New Frontiers, New Challenges.

Chemoimmunotherapy is currently the preferred first-line treatment option for the majority of patients with advanced non-small cell lung cancer without driver genetic alterations. Most of these patients, however, will experience disease progression within the first year after treatment initiation and both patients and their physicians will be confronted with the dilemma of the optimal second-line treatment. Identification of molecular targets, such as KRASG12C, BRAFV600X, METexon14, and human epidermal growth factor receptor 2 mutations, and RET rearrangements offer therapeutic opportunities in pretreated patients with corresponding alterations. For those tumors that do not harbor oncogenic drivers, second-line treatment with docetaxel remains the current standard of care despite modest efficacy. Strategies to challenge docetaxel include the combination of immune checkpoint inhibitors (ICIs) with tyrosine inhibitors of multiple kinases or with DNA damage response inhibitors, antibody-drug conjugates, and locoregional treatments for oligoprogressive disease. Next-generation immunotherapy strategies, such as T-cell engagers, immune-mobilizing monoclonal T-cell receptors, chimeric antigen receptor cell therapy, tumor infiltrating lymphocytes, and T-cell receptor cell therapy are being currently investigated in the quest to reverse resistance to ICIs. Importantly, the advent of these new agents heralds a novel spectrum of toxicities that require both the physician's and the patient's education. Herein, we review current and future strategies aiming to outperform docetaxel after chemoimmunotherapy failure, and we provide practical information on how to best communicate to our patients the unique toxicity aspects associated with immunotherapy.

Balancing risks and rewards: How hematologists discuss uncertainty in allogeneic hematopoietic cell transplantation outcomes.

OBJECTIVE: Allogeneic hematopoietic cell transplant (alloHCT) offers many patients with blood cancers a chance of cure but carries risks. We characterized how hematologists discuss the high-risk, high-reward concept of alloHCT. METHODS: Qualitative analysis of video-recorded virtual encounters of hematologists who routinely perform alloHCT with actors portraying an older man recently diagnosed with high-risk myelodysplastic syndrome. RESULTS: Hematologists (n = 37) were a median age of 44 years, 65% male, and 68% white. They frequently used "teeter-totter" language that juxtaposed alloHCT's risks and rewards in a dynamic, quickly alternating fashion and communicated uncertainty in transplant outcomes. This dialogue oscillated between encouragement about alloHCT's potential for cure and caution about its risks and occurred within single speech turns and in exchanges between hematologist and patient. Fewer hematologists outlined their big-picture stance on transplant's risks and benefits early in the conversation. Meanwhile, hematologists varied in how they counseled patients to manage transplant-related uncertainty and consider treatment decision making. CONCLUSION: Hematologists use "teeter-totter" language to express hope and concern, confidence and uncertainty, and encouragement and caution about the high-risk, high-reward nature of alloHCT. PRACTICE IMPLICATIONS: Teeter-totter language may help frame big-picture content about alloHCT's risks and benefits that is essential for patient education and decision making.

Communication Strategies of Transplant Hematologists in High-Risk Decision-Making Conversations.

PURPOSE: Shared decision making (SDM) is essential to empower patients with blood cancers to make goal-concordant decisions about allogeneic hematopoietic cell transplantation. This study characterizes communication strategies used by hematologists to discuss treatment options and facilitate SDM with patients in this high-risk, high-reward setting. METHODS AND MATERIALS: We recruited US hematologists who routinely perform allogeneic hematopoietic cell transplant through email. Participants conducted up to an hour-long video-recorded encounter with an actor portraying a 67-year-old man with recently diagnosed high-risk myelodysplastic syndrome. We transcribed and qualitatively analyzed video-recorded data. RESULTS: The mean age of participants (N = 37) was 44 years, 65% male, and 68% White. Many hematologists included similar key points in this initial consultation, although varied in how much detail they provided. Their discussion of treatment options included transplant and chemotherapy and less commonly supportive care or clinical trials. They often emphasized transplant's potential for cure, discussed transplant chronologically from pretransplant considerations through the post-transplant course, and outlined risks, complications, and major outcomes. Hematologists referred to several elements that formed the basis of treatment decision making. The strength of their treatment recommendations ranged from strong recommendations for transplant or chemotherapy to deferrals pending more information. Hematologists also varied in the extent to which they indicated the decision was physician-driven, patient-led, or shared. CONCLUSION: The transplant decision-making discussion is complex. Identification of similar content areas used by hematologists can be used as the basis for a communication tool to help hematologists discuss allogeneic hematopoietic cell transplant with patients.

Embedding an Education Intervention about Shared Decision Making into an RCT: Ensuring competency and fidelity.

Objective: To describe the outcomes of training nephrology clinicians and clinical research participants, to use the Best Case/Worst Case Communication intervention, for discussions about dialysis initiation for patients with life-limiting illness, during a randomized clinical trial to ensure competency, fidelity to the intervention, and adherence to study protocols and the intervention throughout the trial. Methods: We enrolled 68 nephrologists at ten study sites and randomized them to receive training or wait-list control. We collected copies of completed graphic aids (component of the intervention), used with study-enrolled patients, to measure fidelity and adherence. Results: We trained 34 of 36 nephrologists to competence and 27 completed the entire program. We received 60 graphic aids for study-enrolled patients for a 73% return rate in the intervention arm. The intervention fidelity score for the graphic aid reflected completion of all elements throughout the study. Conclusion: We successfully taught the Best Case/Worst Case Communication intervention to clinicians as research participants within a randomized clinical trial. Innovation: Decisions about dialysis are an opportunity to discuss prognosis and uncertainty in relation to consideration of prolonged life supporting therapy. Our study reveals a strategy to evaluate adherence to a communication intervention in real time during a clinical study.

Combining Dual Checkpoint Immunotherapy with Ablative Radiation to All Sites of Oligometastatic Non-Small Cell Lung Cancer: Toxicity and Efficacy Results of a Phase 1b Trial.

PURPOSE: Ablative local treatment of all radiographically detected metastatic sites in patients with oligometastatic non-small cell lung cancer (NSCLC) increases progression-free survival (PFS) and overall survival (OS). Prior studies demonstrated the safety of combining stereotactic body radiation therapy (SBRT) with single-agent immunotherapy. We investigated the safety of combining SBRT to all metastatic tumor sites with dual checkpoint, anticytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), and anti-programmed cell death ligand 1 (anti-PD-L1) immunotherapy for patients with oligometastatic NSCLC. METHODS AND MATERIALS: We conducted a phase 1b clinical trial in patients with oligometastatic NSCLC with up to 6 sites of extracranial metastatic disease. All sites of disease were treated with SBRT to a dose of 30 to 50 Gy in 5 fractions. Dual checkpoint immunotherapy was started 7 days after completion of radiation using anti-CTLA-4 (tremelimumab) and anti-PD-L1 (durvalumab) immunotherapy for a total of 4 cycles followed by durvalumab alone until progression or toxicity. RESULTS: Of the 17 patients enrolled in this study, 15 patients received at least 1 dose of combination immunotherapy per protocol. The study was closed early (17 of planned 21 patients) due to slow accrual during the COVID-19 pandemic. Grade 3+ treatment-related adverse events were observed in 6 patients (40%), of which only one was possibly related to the addition of SBRT to immunotherapy. Median PFS was 42 months and median OS has not yet been reached. CONCLUSIONS: Delivering ablative SBRT to all sites of metastatic disease in combination with dual checkpoint immunotherapy did not result in excessive rates of toxicity compared with historical studies of dual checkpoint immunotherapy alone. Although the study was not powered for treatment efficacy results, durable PFS and OS results suggest potential therapeutic benefit compared with immunotherapy or radiation alone in this patient population.

An eHealth system supporting palliative care for patients with non-small cell lung cancer: a randomized trial.

BACKGROUND: In this study, the authors examined the effectiveness of an online support system (Comprehensive Health Enhancement Support System [CHESS]) versus the Internet in relieving physical symptom distress in patients with non-small cell lung cancer (NSCLC). METHODS: In total, 285 informal caregiver-patient dyads were assigned randomly to receive, for up to 25 months, standard care plus training on and access to either use of the Internet and a list of Internet sites about lung cancer (the Internet arm) or CHESS (the CHESS arm). Caregivers agreed to use CHESS or the Internet and to complete bimonthly surveys; for patients, these tasks were optional. The primary endpoint-patient symptom distress-was measured by caregiver reports using a modified Edmonton Symptom Assessment Scale. RESULTS: Caregivers in the CHESS arm consistently reported lower patient physical symptom distress than caregivers in the Internet arm. Significant differences were observed at 4 months (P = .031; Cohen d = .42) and at 6 months (P = .004; d = .61). Similar but marginally significant effects were observed at 2 months (P = .051; d = .39) and at 8 months (P = .061; d = .43). Exploratory analyses indicated that survival curves did not differ significantly between the arms (log-rank P = .172), although a survival difference in an exploratory subgroup analysis suggested an avenue for further study. CONCLUSIONS: The current results indicated that an online support system may reduce patient symptom distress. The effect on survival bears further investigation.

Clinician Perceptions of Barriers and Facilitators for Delivering Early Integrated Palliative Care via Telehealth.

Early integrated palliative care (EIPC) significantly improves clinical outcomes for patients with advanced cancer. Telehealth may be a useful tool to deliver EIPC sustainably and equitably. Palliative care clinicians completed a survey regarding their perceptions of the barriers, facilitators, and benefits of using telehealth video visits for delivering EIPC for patients with advanced lung cancer. Forty-eight clinicians across 22 cancer centers completed the survey between May and July 2022. Most (91.7%) agreed that telehealth increases access to EIPC and simplifies the process for patients to receive EIPC (79.2%). Clinicians noted that the elderly, those in rural areas, and those with less-resourced backgrounds have greater difficulty using telehealth. Perceived barriers were largely patient-based factors, including technological literacy, internet and device availability, and patient preferences. Clinicians agreed that several organizational factors facilitated telehealth EIPC delivery, including technological infrastructure (85.4%), training (83.3%), and support from study coordinators (81.3%). Other barriers included systems-based factors, such as insurance reimbursement and out-of-state coverage restrictions. Patient-, organization-, and systems-based factors are all important to providing and improving access to telehealth EIPC services. Further research is needed to investigate the efficacy of telehealth EIPC and how policies and interventions may improve access to and dissemination of this care modality.

Corrigendum: Myosteatosis as a Shared Biomarker for Sarcopenia and Cachexia Using MRI and Ultrasound.

[This corrects the article DOI: 10.3389/fresc.2022.896114.].

Myosteatosis as a Shared Biomarker for Sarcopenia and Cachexia Using MRI and Ultrasound.

Purpose: Establish bedside biomarkers of myosteatosis for sarcopenia and cachexia. We compared ultrasound biomarkers against MRI-based percent fat, histology, and CT-based muscle density among healthy adults and adults undergoing treatment for lung cancer. Methods: We compared ultrasound and MRI myosteatosis measures among young healthy, older healthy, and older adults with non-small cell lung cancer undergoing systemic treatment, all without significant medical concerns, in a cross-sectional pilot study. We assessed each participant's rectus femoris ultrasound-based echo intensity (EI), shear wave elastography-based shear wave speed, and MRI-based proton density fat-fraction (PDFF). We also assessed BMI, rectus femoris thickness and cross-sectional area. Rectus femoris biopsies were taken for all older adults (n = 20) and we analyzed chest CT scans for older adults undergoing treatment (n = 10). We determined associations between muscle assessments and BMI, and compared these assessments between groups. Results: A total of 10 young healthy adults, 10 older healthy adults, and 10 older adults undergoing treatment were recruited. PDFF was lower in young adults than in older healthy adults and older adults undergoing treatment (0.3 vs. 2.8 vs. 2.9%, respectively, p = 0.01). Young adults had significantly lower EI than older healthy adults, but not older adults undergoing treatment (48.6 vs. 81.8 vs. 75.4, p = 0.02). When comparing associations between measures, PDFF was strongly associated with EI (ρ = 0.75, p < 0.01) and moderately negatively associated with shear wave speed (ρ = -0.49, p < 0.01) but not BMI, whole leg cross-sectional area, or rectus femoris cross-sectional area. Among participants with CT scans, paraspinal muscle density was significantly associated with PDFF (ρ = -0.70, p = 0.023). Histological markers of inflammation or degradation did not differ between older adult groups. Conclusion: PDFF was sensitive to myosteatosis between young adults and both older adult groups. EI was less sensitive to myosteatosis between groups, yet EI was strongly associated with PDFF unlike BMI, which is typically used in cachexia diagnosis. Our results suggest that ultrasound measures may serve to determine myosteatosis at the bedside and are more useful diagnostically than traditional weight assessments like BMI. These results show promise of using EI, shear wave speed, and PDFF proxies of myosteatosis as diagnostic and therapeutic biomarkers of sarcopenia and cachexia.

Best Case/Worst Case: protocol for a multisite randomised clinical trial of a scenario planning intervention for patients with kidney failure.

INTRODUCTION: Given the burdens of treatment and poor prognosis, older adults with kidney failure would benefit from improved decision making and palliative care to clarify goals, address symptoms, and reduce unwanted procedures. Best Case/Worst Case (BC/WC) is a communication tool that uses scenario planning to support patients' decision making. This article describes the protocol for a multisite, cluster randomised trial to test the effect of training nephrologists to use the BC/WC communication tool on patient receipt of palliative care, and quality of life and communication. METHODS AND ANALYSIS: We are enrolling attending nephrologists, at 10 study sites in the USA, who see outpatients with advanced chronic kidney disease considering dialysis. We aim to enrol 320 patients with an estimated glomerular filtration rate of ≤24 mL/min/1.73 m2 who are age 60 and older and have a predicted survival of 18 months or less. Nephrologists will be randomised in a 1:1 ratio to receive training to use the communication tool (intervention) at study initiation or after study completion (wait-list control). Patients in the intervention group will receive care from a nephrologist trained to use the BC/WC communication tool. Patients in the control group will receive usual care. Using chart review and surveys of patients and caregivers, we will test the efficacy of the BC/WC intervention with receipt of palliative care as the primary outcome. Secondary outcomes include intensity of treatment at the end of life, the effect of the intervention on quality of communication (QOC) between nephrologists and patients (using the QOC scale), the change in quality of life (using the Functional Assessment of Chronic Illness Therapy-Palliative Care scale) and receipt of dialysis. ETHICS AND DISSEMINATION: Approvals have been granted by the Institutional Review Board at the University of Wisconsin (ID: 2022-0193), with each study site ceding review to the primary IRB. All nephrologists will be consented and given a copy of the consent form. No patients or caregivers will be recruited or consented until their nephrology provider has chosen to participate in the study. Results will be disseminated via submission for publication in a peer-reviewed journal and at national meetings. TRIAL REGISTRATION NUMBER: NCT04466865.