Financial toxicity in early-phase cancer clinical trial participants.

BACKGROUND: Little is known about financial toxicity in early-phase clinical trial (EP-CT) participants. This study sought to describe financial toxicity in EP-CT participants and assess associations with patient characteristics and patient-reported outcomes (PROs). METHODS: Prospectively enrolled EP-CT participants from were followed from April 2021 through January 2023. Participants completed the Comprehensive Score for Financial Toxicity (<26 = financial toxicity) at time of treatment. Quality of life (QOL), symptoms, coping, and resource concerns were surveyed. Associations of financial toxicity with patient characteristics, PROs, and clinical outcomes were explored. RESULTS: Of 261 eligible patients, 197 completed baseline assessments (75.5%, median age = 63.4 years [31.8-88.6], 57.4% female). Most common cancers were gastrointestinal (33.0%) and breast (20.8%). More than one third (34.0%) of patients reported financial toxicity. Patients with financial toxicity were more likely to be <65 years (70.2% vs 48.5%, p = .004), unemployed (45.5% vs 16.9%, p < .001), not have attended college (53.1% vs 26.4%, p = .002), and have income <$60,000 (59.7% vs 25.4%, p < .001). In adjusted models, patients with financial toxicity reported lower QOL (B = -6.66, p = .004) and acceptance (B = -0.78, p = .002), and increased self-blame (B = 0.87, p < .001). They were more likely to have concerns regarding housing (10.6% vs 2.3%, p = .025), bills (31.8% vs 3.8%, p < .001), food (9.1% vs 0.8%, p = .006), and employment (21.2% vs 1.5%, p < .001). There was no difference in time on trial (hazard ratio, 1.03; p = .860) or survival (hazard ratio, 1.16; p = .496). CONCLUSIONS: More than one third of EP-CT participants reported financial toxicity. Factors associated with financial toxicity and demonstrated novel associations among financial toxicity with QOL, coping, and resource concerns were identified, highlighting the need to address financial toxicity among this population.

Maryland's Global Budget Revenue Payment Model and Shifts in the Surgical Site of Care Among Medicare Beneficiaries.

OBJECTIVE: To assess the association between the Global Budget Revenue (GBR) payment model and shifts to the outpatient setting for surgical procedures among Medicare fee-for-service beneficiaries in Maryland versus control states. SUMMARY BACKGROUND DATA: The GBR model provides fixed global payments to hospitals to reduce spending growth and incentivize hospitals to reduce the costs of care while improving care quality. Since surgical care is a major contributor to hospital spending, the GBR model might accelerate the ongoing shift from the inpatient to the outpatient setting to generate additional savings. METHODS: A difference-in-differences (DiD) design was used to compare changes in surgical care settings over time from pre-GBR (2011-2013) to post-GBR (2014-2018) for Maryland versus control states for common surgeries that could be performed in the outpatient setting. A cross-sectional approach was used to compare the difference in care settings in 2018 for total knee arthroplasty which was on Medicare's Inpatient-Only List before then. RESULTS: We studied 47,542 surgical procedures from 44,410 beneficiaries in Maryland and control states. GBR's 2014 implementation was associated with an acceleration in the shift from inpatient to outpatient settings for surgical procedures in Maryland (DiD: 3.9 percentage points, 95% CI: 2.3, 5.4). Among patients undergoing total knee arthroplasty in 2018, the proportion of outpatient surgeries in Maryland was substantially higher than that in control states (difference: 27.6 percentage points, 95% CI: 25.6, 29.6). CONCLUSIONS: Implementing Maryland's GBR payment model was associated with an acceleration in the shift from inpatient to outpatient hospital settings for surgical procedures.

Learning about and living with toxicity: a qualitative study of patients receiving immune checkpoint inhibitors for melanoma or lung cancer and their caregivers.

BACKGROUND/OBJECTIVE: Immune checkpoint inhibitors (ICIs) have revolutionized treatment for melanoma and lung cancer and are in widespread use. This study aims to describe how patients and caregivers learn about ICI toxicities and their perceptions and experiences of toxicity. METHODS: We conducted a qualitative study of 42 patients with advanced non-small cell lung cancer (NSCLC; n = 16) or melanoma (n = 26) who were initiating or discontinuing an ICI and their caregivers (n = 9). We conducted in-depth interviews to explore patients' and caregivers' experiences learning about and living with ICI side effects. We audio-recorded the first oncology visit after enrollment. We used a framework approach to code interview and visit transcripts and synthesized codes into themes. RESULTS: The median age of patients was 67; 68% were male. Themes of participant interviews and clinician-patient dialogue included: (i) Patients initiating an ICI received extensive information about side effects, which some patients found overwhelming or scary and difficult to absorb; (ii) patients who were deterred by fear of toxicity ultimately proceeded with treatment because of oncologist encouragement or the sense of no alternative; (iii) participants found hope in the association between toxicity and ICI efficacy; (iv) caregivers helped patients navigate the deluge of information and uncertainty related to ICIs. Participants suggested ways to improve ICI side effect education, such as incorporating patient stories. CONCLUSION: Patients perceived that ICI toxicity counseling was overwhelming yet were encouraged by oncologists' reassurance that serious side effects were manageable and by the framing of toxicity as a sign of efficacy. We identified opportunities to improve communication of ICI risks and benefits.

Stepped Palliative Care for Patients With Advanced Lung Cancer: A Randomized Clinical Trial.

Importance: Despite the evidence for early palliative care improving outcomes, it has not been widely implemented in part due to palliative care workforce limitations. Objective: To evaluate a stepped-care model to deliver less resource-intensive and more patient-centered palliative care for patients with advanced cancer. Design, Setting, and Participants: Randomized, nonblinded, noninferiority trial of stepped vs early palliative care conducted between February 12, 2018, and December 15, 2022, at 3 academic medical centers in Boston, Massachusetts, Philadelphia, Pennsylvania, and Durham, North Carolina, among 507 patients who had been diagnosed with advanced lung cancer within the past 12 weeks. Intervention: Step 1 of the intervention was an initial palliative care visit within 4 weeks of enrollment and subsequent visits only at the time of a change in cancer treatment or after a hospitalization. During step 1, patients completed a measure of quality of life (QOL; Functional Assessment of Cancer Therapy-Lung [FACT-L]; range, 0-136, with higher scores indicating better QOL) every 6 weeks, and those with a 10-point or greater decrease from baseline were stepped up to meet with the palliative care clinician every 4 weeks (intervention step 2). Patients assigned to early palliative care had palliative care visits every 4 weeks after enrollment. Main Outcomes and Measures: Noninferiority (margin = -4.5) of the effect of stepped vs early palliative care on patient-reported QOL on the FACT-L at week 24. Results: The sample (n = 507) mostly included patients with advanced non-small cell lung cancer (78.3%; mean age, 66.5 years; 51.4% female; 84.6% White). The mean number of palliative care visits by week 24 was 2.4 for stepped palliative care and 4.7 for early palliative care (adjusted mean difference, -2.3; P < .001). FACT-L scores at week 24 for the stepped palliative care group were noninferior to scores among those receiving early palliative care (adjusted FACT-L mean score, 100.6 vs 97.8, respectively; difference, 2.9; lower 1-sided 95% confidence limit, -0.1; P < .001 for noninferiority). Although the rate of end-of-life care communication was also noninferior between groups, noninferiority was not demonstrated for days in hospice (adjusted mean, 19.5 with stepped palliative care vs 34.6 with early palliative care; P = .91). Conclusions and Relevance: A stepped-care model, with palliative care visits occurring only at key points in patients' cancer trajectories and using a decrement in QOL to trigger more intensive palliative care exposure, resulted in fewer palliative care visits without diminishing the benefits for patients' QOL. While stepped palliative care was associated with fewer days in hospice, it is a more scalable way to deliver early palliative care to enhance patient-reported outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT03337399.

Prognostic communication about lung cancer in the precision oncology era: A multiple-perspective qualitative study.

BACKGROUND: Although most patients with cancer prefer to know their prognosis, prognostic communication between oncologists and patients is often insufficient. Targeted therapies for lung cancer improve survival yet are not curative and produce variable responses. This study sought to describe how oncologists communicate about prognosis with patients receiving targeted therapies for lung cancer. METHODS: This qualitative study included 39 patients with advanced lung cancer with targetable mutations, 14 caregivers, and 10 oncologists. Semistructured interviews with patients and caregivers and focus groups or interviews with oncologists were conducted to explore their experiences with prognostic communication. One oncology follow-up visit was audio-recorded per patient. A framework approach was used to analyze interview transcripts, and a content analysis of patient-oncologist dialogue was conducted. Themes were identified within each source and then integrated across sources to create a multidimensional description of prognostic communication. RESULTS: Six themes in prognostic communication were identified: Patients with targetable mutations develop a distinct identity in the lung cancer community that affects their information-seeking and self-advocacy; oncologists set high expectations for targeted therapy; the uncertain availability of new therapies complicates prognostic discussions; patients and caregivers have variable information preferences; patients raise questions about progression by asking about physical symptoms or scan results; and patients' expectations of targeted therapy influence their medical decision-making. CONCLUSIONS: Optimistic patient-oncologist communication shapes the expectations of patients receiving targeted therapy for lung cancer and affects their decision-making. Further research and clinical guidance are needed to help oncologists to communicate uncertain outcomes effectively.

Palliative care in the emergency department: A qualitative study exploring barriers, facilitators, desired clinician qualities, and future directions.

OBJECTIVE: To describe the perceived qualities of successful palliative care (PC) providers in the emergency department (ED), barriers and facilitators to ED-PC, and clinicians' perspectives on the future of ED-PC. METHOD: This qualitative study using semi-structured interviews was conducted in June-August 2020. Interviews were analyzed via a two-phase Rapid Analysis. The study's primary outcomes (innovations in ED-PC during COVID) are published elsewhere. In this secondary analysis, we examine interviewee responses to broader questions about ED-PC currently and in the future. RESULTS: PC providers perceived as successful in their work in the ED were described as autonomous, competent, flexible, fast, and fluent in ED language and culture. Barriers to ED-PC integration included the ED environment, lack of access to PC providers at all times, the ED perception of PC, and the lack of a supporting financial model. Facilitators to ED-PC integration included proactive identification of patients who would benefit from PC, ED-focused PC education and tools, PC presence in the ED, and data supporting ED-PC. Increased primary PC education for ED staff, increased automation, and innovative ED-PC models were seen as areas for future growth. SIGNIFICANCE OF RESULTS: Our findings provide useful information for PC programs considering expanding their ED presence, particularly as this is the first study to our knowledge that examines traits of successful PC providers in the ED environment. Our findings also suggest that, despite growth in the arena of ED-PC, barriers and facilitators remain similar to those identified previously. Future research is needed to evaluate the impact that ED-PC initiatives may have on patient and system outcomes, to identify a financial model to maintain ED-PC integration, and to examine whether perceptions of successful providers align with objective measures of the same.

Knowledge About Risks, Benefits, and Curative Potential of Immunotherapy Among Patients with Advanced Cancer.

BACKGROUND: Immunotherapy is the first-line treatment for melanoma and lung cancer and brings new risks of immune-related adverse events. We aimed to describe patients' knowledge about risks, benefits, and goals of immunotherapy. MATERIALS AND METHODS: We conducted a cross-sectional study of patients with advanced melanoma or non-small cell lung cancer that used a 9-item knowledge survey and questions from the Prognosis and Treatment Perceptions Questionnaire. RESULTS: We surveyed 105 participants (57 with melanoma, 48 with lung cancer) with median age 69 years (range 36-89). Participants' responses revealed knowledge deficits about immunotherapy mechanism of action and lack of awareness about the timing and severity of side effects. One third (34%; 36/105) of participants reported that the primary goal of their treatment is to cure their cancer. CONCLUSION: Given the widespread use of immunotherapy, patients would benefit from educational tools so that they know what to expect regarding side effects and prognosis.

Clinical Outcomes of Patients with Metastatic Cancer Receiving Immune Checkpoint Inhibitors in the Inpatient Setting.

BACKGROUND: As indications for immune checkpoint inhibitor (ICI) therapy have increased in recent years, so has the proportion of patients eligible for this type of therapy. However, a lack of data exists about the risks and benefits of ICI therapy in hospitalized patients, who tend to be frailer and sicker than patients enrolled in clinical trials. MATERIAL AND METHODS: We conducted a retrospective cohort study among hospitalized patients with metastatic solid tumors who received ICI therapy at a large academic cancer center over the course of 4 years. We analyzed the characteristics and outcomes of these patients and identified demographic and clinical factors that could be used to predict mortality. RESULTS: During the 4-year study period, 106 patients were treated with ICI therapy while admitted to the hospital; 70 (66%) had Eastern Cooperative Oncology Group Performance Status ≥2, which would have prevented them from enrolling in most clinical trials of ICIs. Fifty-two patients (49%) died either during admission or within 30 days of discharge; median overall survival was 1.0 month from discharge, and 16 patients (15%) were alive 6 months after discharge. Independent predictors of death following receipt of inpatient ICI included a diagnosis of non-small cell lung cancer relative to melanoma and prior treatment with two or more lines of therapy. CONCLUSION: The poor overall outcomes observed in this study may give clinicians pause when considering ICI therapy for hospitalized patients, particularly those with characteristics that are associated with a greater risk of mortality. IMPLICATIONS FOR PRACTICE: Immunotherapy strategies for patients with cancer are rapidly evolving and their use is expanding, but not all patients will develop a response, and secondary toxicity can be significant and challenging. This is especially evident in hospitalized patients, where the economic cost derived from inpatient immune checkpoint inhibitor (ICI) administration is important and the clinical benefit is sometimes unclear. The poor overall outcomes evidenced in the ICI inpatient population in this study highlight the need to better identify the patients that will respond to these therapies, which will also help to decrease the financial burden imposed by these highly priced therapies.

Temporal Trends and Outcomes Among Patients Admitted for Immune-Related Adverse Events: A Single-Center Retrospective Cohort Study from 2011 to 2018.

BACKGROUND: The aim of this study was to characterize severe immune-related adverse events (irAEs) seen among hospitalized patients and to examine risk factors for irAE admissions and clinically relevant outcomes, including length of stay, immune checkpoint inhibitor (ICI) discontinuation, readmission, and death. METHODS: Patients who received ICI therapy (ipilimumab, pembrolizumab, nivolumab, atezolizumab, durvalumab, avelumab, or any ICI combination) at Massachusetts General Hospital (MGH) and were hospitalized at MGH following ICI initiation between January 1, 2011, and October 24, 2018, were identified using pharmacy and hospital admission databases. Medical records of all irAE admissions were reviewed, and specialist review with defined criteria was performed. Demographic data, relevant clinical history (malignancy type and most recent ICI regimen), and key admission characteristics, including dates of admission and discharge, immunosuppressive management, ICI discontinuation, readmission, and death, were collected. RESULTS: In total, 450 admissions were classified as irAE admissions and represent the study's cohort. Alongside the increasing use of ICIs at our institution, the number of patients admitted to MGH for irAEs has gradually increased every year from 9 in 2011 to 92 in 2018. The hospitalization rate per ICI recipient has declined over that same time period (25.0% in 2011 to 8.5% in 2018). The most common toxicities leading to hospitalization in our cohort were gastrointestinal (30.7%; n = 138), pulmonary (15.8%; n = 71), hepatic (14.2%; n = 64), endocrine (12.2%; n = 55), neurologic (8.4%; n = 38), cardiac (6.7%; n = 30), and dermatologic (4.4%; n = 20). Multivariable logistic regression revealed statistically significant increases in irAE admission risk for CTLA-4 monotherapy recipients (odds ratio [OR], 2.02; p < .001) and CTLA-4 plus PD-1 combination therapy recipients (OR, 1.88; p < .001), relative to PD-1/PD-L1 monotherapy recipients, and patients with multiple toxicity had a 5-fold increase in inpatient mortality. CONCLUSION: This study illustrates that cancer centers must be prepared to manage a wide variety of irAE types and that CTLA-4 and combination ICI regimens are more likely to cause irAE admissions, and earlier. In addition, admissions for patients with multi-organ involvement is common and those patients are at highest risk of inpatient mortality. IMPLICATIONS FOR PRACTICE: The number of patients admitted to Massachusetts General Hospital for immune-related adverse events (irAEs) has gradually increased every year and the most common admissions are for gastrointestinal (30.7%), pulmonary (15/8%), and hepatic (14.2%) events. Readmission rates are high (29% at 30 days, 49% at 180 days) and 64.2% have to permanently discontinue immune checkpoint inhibitor therapy. Importantly, multiple concurrent toxicities were seen in 21.6% (97/450) of irAE admissions and these patients have a fivefold increased risk of inpatient death.

Performance status and end-of-life care among adults with non-small cell lung cancer receiving immune checkpoint inhibitors.

BACKGROUND: Adults with impaired performance status (PS) often receive immune checkpoint inhibitors (ICIs) for advanced non-small cell lung cancer (NSCLC) despite limited efficacy data and unknown effects on end-of-life care. METHODS: This was a retrospective, single-site study of 237 patients with advanced NSCLC who initiated ICI treatment from 2015 to 2017. Cox regression was used to compare the overall survival (OS) of patients who had impaired PS (≥2) at the start of ICI treatment with those who had PS 0 or 1 using Cox regression. Logistic regression was conducted to analyze the association between ICI use in the last 30 days of life and the use of end-of-life health care. RESULTS: The patient mean age at ICI initiation was 67 years (range, 37-91 years), and 35.4% of patients had PS ≥2. Most patients (80.8%) received ICI as second-line or later therapy. The median OS was 4.5 months in patients with PS ≥2 and 14.3 months in those with PS 0 or 1 (hazard ratio, 2.5; P < .0001). Among the patients who died (n = 184), 28.8% who had PS ≥2 received ICIs in their last 30 days of life compared with 10.8% of those who had PS 0 or 1 (P = .002). Receipt of ICI in the last 30 days of life was associated with decreased hospice referral (odds ratio, 0.29; P = .008) and increased in-hospital deaths (odds ratio, 6.8; P = .001), independent of PS. CONCLUSIONS: Adults with advanced NSCLC and impaired PS experience significantly shorter survival after ICI treatment and receive ICIs near death more often than those with better PS. Receipt of an ICI near death was associated with lower hospice use and an increased risk of death in the hospital. These results underscore the need for high-quality communication about potential tradeoffs of ICIs, particularly among adults receiving ICIs as second-line or later therapy.

Rates of Recovery to Pre-Fracture Function in Older Persons with Hip Fracture: an Observational Study.

BACKGROUND: Knowledge about expected recovery after hip fracture is essential to help patients and families set realistic expectations and plan for the future. OBJECTIVES: To determine rates of functional recovery in older adults who sustained a hip fracture based on one's previous function. DESIGN: Observational study. PARTICIPANTS: We identified subjects who sustained a hip fracture while enrolled in the nationally representative Health and Retirement Study (HRS) using linked Medicare claims. HRS interviews subjects every 2 years. Using information from interviews collected during the interview preceding the fracture and the first interview 6 or more months after the fracture, we determined the proportion of subjects who returned to pre-fracture function. MAIN MEASURES: Functional outcomes of interest were: (1) ADL dependency, (2) mobility, and (3) stair-climbing ability. We examined baseline characteristics associated with a return to: (1) ADL independence, (2) walking one block, and (3) climbing a flight of stairs. KEY RESULTS: A total of 733 HRS subjects ≥65 years of age sustained a hip fracture (mean age 84 ± 7 years, 77 % female). Thirty-one percent returned to pre-fracture ADL function, 34 % to pre-fracture mobility function, and 41 % to pre-fracture climbing function. Among those who were ADL independent prior to fracture, 36 % returned to independence, 27 % survived but needed ADL assistance, and 37 % died. Return to ADL independence was less likely for those ≥85 years old (26 % vs. 44 %), with dementia (8 % vs. 39 %), and with a Charlson comorbidity score >2 (23 % vs. 44 %). Results were similar for those able to walk a block and for those able to climb a flight of stairs prior to fracture. CONCLUSIONS: Recovery rates are low, even among those with higher levels of pre-fracture functional status, and are worse for patients who are older, cognitively impaired, and who have multiple comorbidities.

How California Prepared for Implementation of Physician-Assisted Death: A Primer.

Physician-assisted death is now legal in California, and similar laws are being considered in many other states. The California law includes safeguards, yet health care providers will face practical and ethical issues while implementing physician-assisted death that are not addressed by the law. To help providers and health care facilities in California prepare to provide optimal care to patients who inquire about physician-assisted death, we brought together experts from California, Oregon, and Washington. We convened a conference of 112 stakeholders in December 2015, and herein present their recommendations. Themes of recommendations regarding implementation include (1) institutions should develop and revise physician-assisted death policies; (2) legal physician-assisted death will have implications for California's culturally and socioeconomically diverse population, and for patients from vulnerable groups; (3) conscientious objection and moral distress for health care providers must be considered; and (4) palliative care is essential to the response to the law. The expert conference participants' insights are a valuable guide, both for providers and health care facilities in California planning or revising their response, and for other jurisdictions where physician-assisted death laws are being considered or implemented.

Vortioxetine for major depressive disorder, vasomotor, and cognitive symptoms associated with the menopausal transition.

BACKGROUND: In a preliminary trial, we assessed the efficacy of vortioxetine for major depressive disorder (MDD) during the menopausal transition. Secondary outcomes included hot flashes (HFs), anxiety, and cognitive complaints. METHODS: Perimenopausal and early postmenopausal women with MDD (N = 27) received 8 weeks of open-label, flexible-dose treatment with vortioxetine. The Montgomery-Åsberg Depression Rating Scale (MADRS) was the primary outcome measure. Secondary measures included: HF frequency, the Greene Climacteric Scale (GCS), Menopause-Specific Quality of Life Questionnaire (MEN-QOL), Beck Anxiety Inventory (BAI), Cognitive and Physical Functioning Questionnaire (CPFQ), Digit Symbol Substitution Test (DSST), and Cogstate testing. RESULTS: Of the 27 women, 24 (88.8%) were evaluated (≥1 follow-up), and 21 (77.8%) completed the study; 1 discontinued because of adverse effects. The mean MADRS score decreased significantly (P = .0001) from 31.3 (standard deviation [SD] = 5.5) at pretreatment to 8.1 (SD = 7.8) at posttreatment. The depression response rate (≥50% reduction in MADRS) and remission rate (final MADRS ≤10) were 75% and 70.8%, respectively. GCS, MEN-QOL, BAI, CPFQ, and DSST scores improved significantly (P = .0030, P = .0001, P = .0001, P = .0001, and P = .0133, respectively); Cogstate test scores did not. Frequency and severity of HFs improved significantly (P = .0291 and P = .0299, respectively). CONCLUSIONS: These data support further study of vortioxetine for treating menopausal depression and associated symptoms.

The challenges of symptom management for patients with multimorbidity in research and practice: a thematic review.

Multimorbidity, the presence of multiple coexisting diseases or conditions, afflicts the majority of older adults, and is associated with increased mortality and healthcare utilization. In addition, multimorbidity negatively impacts quality of life and increases symptom burden. Yet, there is a dearth of evidence on how to best manage symptoms in patients with multimorbidity. Research in this area has been hampered by inconsistent definitions of multimorbidity and challenges in outcome measurement. Investigations of symptom management strategies in specific disease states, like cancer, typically exclude medically complex patients. In the absence of evidence, the American Geriatrics Society's recommendations for the care of adults with multimorbidity provide a useful starting point for clinicians. We present a case to demonstrate how the AGS recommendations can be tailored to the situation of symptom management in patients with multimorbidity. We also present suggestions for future research directions.

Why and How to Integrate Early Palliative Care Into Cutting-Edge Personalized Cancer Care.

Early palliative care, palliative care integrated with oncology care early in the course of illness, has myriad benefits for patients and their caregivers, including improved quality of life, reduced physical and psychological symptom burden, enhanced prognostic awareness, and reduced health care utilization at the end of life. Although ASCO and others recommend early palliative care for all patients with advanced cancer, widespread implementation of early palliative care has not been realized because of barriers such as insufficient reimbursement and a palliative care workforce shortage. Investigators have recently tested several implementation strategies to overcome these barriers, including triggers for palliative care consultations, telehealth delivery, navigator-delivered interventions, and primary palliative care interventions. More research is needed to identify mechanisms to distribute palliative care optimally and equitably. Simultaneously, the transformation of the oncology treatment landscape has led to shifts in the supportive care needs of patients and caregivers, who may experience longer, uncertain trajectories of cancer. Now, palliative care also plays a clear role in the care of patients with hematologic malignancies and may be beneficial for patients undergoing phase I clinical trials and their caregivers. Further research and clinical guidance regarding how to balance the risks and benefits of opioid therapy and safely manage cancer-related pain across this wide range of settings are urgently needed. The strengths of early palliative care in supporting patients' and caregivers' coping and centering decisions on their goals and values remain valuable in the care of patients receiving cutting-edge personalized cancer care.

Patient and Caregiver Experience With the Hope and Prognostic Uncertainty of Immunotherapy: A Qualitative Study.

PURPOSE: Immunotherapy has improved survival for patients with melanoma and non-small cell lung cancer (NSCLC). Yet, as responses vary widely, immunotherapy also introduces challenges in prognostic communication. In this study, we sought to explore how patients and caregivers learned about the goal of immunotherapy and their experience of living with uncertainty. MATERIALS AND METHODS: We conducted a qualitative study of patients with stage III or IV melanoma or stage IV NSCLC within 12 weeks of initiating or 12 months of discontinuing immunotherapy, and their caregivers. We conducted in-depth interviews with participants to explore how they learned about immunotherapy from oncology clinicians and how they experienced uncertainty. We used a framework approach to analyze interview transcripts and synthesized concepts into themes. RESULTS: Forty-two patients and 10 caregivers participated; median age was 67 years and most were male (68%), white (95%), married (61%), and had melanoma (62%). We identified four themes: (1) the oncology team shaped participants' hopeful expectations of immunotherapy, including as a potential cure among those with melanoma; (2) distress related to prognostic uncertainty particularly affected patients who experienced toxicity or progressive disease; (3) patients who did not have long-term responses experienced overwhelming disappointment; and (4) some patients and caregivers had conflicting preferences for prognostic information. Participants provided suggestions to improve education and underscored unmet psychosocial needs. CONCLUSION: Patients and caregivers held optimistic expectations of immunotherapy, which resulted in heightened disappointment among the subset with progression or toxicity. Clinicians should elicit information preferences of both patients and caregivers, as these may be disparate. Our results highlight the need to optimize prognostic communication and support for living with uncertainty among patients receiving immunotherapy.

Learning About and Living With Toxicity: A Qualitative Study of Patients Receiving Immune Checkpoint Inhibitors For Melanoma or Lung Cancer and Their Caregivers.

Background/Objective: Immune checkpoint inhibitors (ICIs) have revolutionized treatment for melanoma and lung cancer and are in widespread use. This study aims to describe how patients and caregivers learn about ICI toxicities and their perceptions and experiences of toxicity. Methods: We conducted a qualitative study of 42 patients with advanced non-small cell lung cancer (NSCLC; n = 16) or melanoma (n = 26) who were initiating or discontinuing an ICI and their caregivers (n = 9). We conducted in-depth interviews to explore patients' and caregivers' experiences learning about and living with ICI side effects. We audio-recorded the first oncology visit after enrollment. We used a framework approach to code interview and visit transcripts and synthesized codes into themes. Results: The median age of patients was 67; 68% were male. Themes of participant interviews and clinician-patient dialogue included: i) Patients initiating an ICI received extensive information about side effects, which some patients found overwhelming or scary and difficult to absorb; ii) Patients who were deterred by fear of toxicity ultimately proceeded with treatment because of oncologist encouragement or the sense of no alternative; iii) participants found hope in the association between toxicity and ICI efficacy; iv) caregivers helped patients navigate the deluge of information and uncertainty related to ICIs. Participants suggested ways to improve ICI side effect education, such as incorporating patient stories. Conclusion: Patients perceived that ICI toxicity counseling was overwhelming yet were encouraged by oncologists' reassurance that serious side effects were manageable and by the framing of toxicity as a sign of efficacy. We identified opportunities to improve communication of ICI risks and benefits.

Time Toxicity Experienced by Early-Phase Cancer Clinical Trial Participants.

PURPOSE: Early-phase clinical trials (EP-CTs) are designed to determine optimal dosing, tolerability, and preliminary activity of novel cancer therapeutics. Little is known about the time that patients spend interacting with the health care system (eg, time toxicity) while participating in these studies. METHODS: We retrospectively reviewed the electronic health records of consecutive patients enrolled in EP-CTs from 2017 to 2019 to obtain baseline characteristics and number of health care-associated days, defined as all inpatient and outpatient visits while on trial. We used univariable and multivariable analyses to identify predictors of increased time toxicity, defined as the proportion of health care-associated days among total days on trial. For ease of interpretation, we created a dichotomous variable, with high time toxicity defined as ≥20% health care-associated days during time on trial and used regression models to evaluate relationships between time toxicity and clinical outcomes. RESULTS: Among 408 EP-CT participants (mean age, 60.5 years [standard deviation, SD, 12.6]; 56.5% female; 88.2% White; 96.0% non-Hispanic), patients had an average of 22.5% health care-associated days while on trial (SD, 13.8%). Those with GI (B = 0.07; P = .002), head/neck (B = 0.09; P = .004), and breast (B = 0.06; P = .015) cancers and those with worse performance status (B = 0.04; P = .017) and those receiving targeted therapies (B = 0.04; P = .014) experienced higher time toxicity. High time toxicity was associated with decreased disease response rates (odds ratio, 0.07; P < .001), progression-free survival (hazard ratio [HR], 2.10; P < .001), and overall survival (HR, 2.16; P < .001). CONCLUSION: In this cohort of EP-CT participants, patients spent more than one-fifth of days on trial with health care contact. We identified characteristics associated with higher time toxicity and found that high toxicity correlated with worse clinical outcomes. These data could help inform patient-clinician discussions about EP-CTs, guide future trial design, and identify at-risk patients.

Goals of Care Conversations Documented By an Embedded Emergency Department-Palliative Care Team During COVID.

Background: There has been growing interest around integrating palliative care (PC) into emergency department (ED) practice but concern about feasibility and impact. In 2020, as the COVID pandemic was escalating, our hospital's ED and PC leadership created a new service of PC clinicians embedded in the ED. Objectives: To describe the clinical work of the embedded ED-PC team, in particular what was discussed during goals of care conversations. Design: Prospective patient identification followed by retrospective electronic health record chart extraction and analysis. Settings/Subjects: Adult ED patients in an academic medical center in the United States. Measurements/Results: The embedded ED-PC team saw 159 patients, whose mean age was 77.5. Nearly all patients were admitted, 48.0% had confirmed or presumed COVID, and overall mortality was 29.1%. Of the patients seen, 58.5% had a serious illness conversation documented as part of the consult. The most common topics addressed were patient (or family) illness understanding (96%), what was most important (92%), and a clinical recommendation (91%). Clinicians provided a prognostic estimate in 57/93 (61.3%) of documented discussions. In the majority of cases where prognosis was discussed, it was described as poor. Conclusion: Specialist PC clinicians embedded in the ED can engage in high-quality goals of care conversations that have the potential to align patients' hospital trajectory with their preferences.

Study protocol for a randomized trial of a supportive care mobile application to improve symptoms, coping, and quality of life in patients with advanced non-small cell lung cancer.

Patients with advanced non-small cell lung cancer (NSCLC) often experience burdensome symptoms, emotional distress, and poor quality of life (QOL). While national guidelines recommend early palliative care to address these supportive care needs, most patients with advanced NSCLC lack access to such comprehensive care. Our aim in the current study is to test a novel model of palliative care delivery and use of innovative technology to evaluate the feasibility, acceptability, and preliminary efficacy of a supportive care mobile application (app) for improving symptom management and adaptive coping in patients with advanced NSCLC. We will enroll 120 patients with unresectable Stage III or IV NSCLC diagnosed within the past 12 weeks receiving care with palliative intent at a major academic comprehensive cancer center and its community affiliates. The study will take place in two phases, the first of which will be dedicated to adapting an evidence-based, early palliative care treatment guide and prior supportive care mobile app intervention to address the specific symptom management and coping needs of patients with advanced NSCLC. The second phase of the study will be a two-group, randomized controlled trial. Study patients will complete baseline self-report measures of symptoms, mood, coping skills, and QOL, after which they will be randomized to receive either the mobile app intervention combined with usual oncology care or usual oncology care alone. Intervention patients will use a tablet computer to self-administer the mobile app, which consists of six modules that teach evidence-based skills for managing burdensome symptoms and coping effectively with advanced cancer and its treatment. At 12 weeks follow up, patients in both groups will repeat the same self-report measures. We will use descriptive statistics to determine feasibility metrics of enrollment and retention rates. For secondary self-report measures, we will use linear regression controlling for baseline values. The results of the present study will contribute to a growing body of evidence regarding the supportive care needs of patients with advanced cancer and will have implications for how best to use innovative technology to widely disseminate comprehensive supportive care services to all patients who may benefit. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier[NCT04629300].