Randomized Controlled Trial of a Nurse-Led Brief Behavioral Intervention for Dyspnea in Patients With Advanced Lung Cancer.

PURPOSE: In patients with lung cancer, dyspnea is one of the most prevalent and disabling symptoms, for which effective treatments are lacking. We examined the efficacy of a nurse-led brief behavioral intervention to improve dyspnea in patients with advanced lung cancer. METHODS: Patients with advanced lung cancer reporting at least moderate breathlessness (n = 247) were enrolled in a randomized trial of a nurse-led two-session intervention (focused on breathing techniques, postural positions, and fan therapy) versus usual care. At baseline and weeks 8 (primary end point), 16, and 24, participants completed measures of dyspnea (Modified Medical Research Council Dyspnea Scale [mMRCDS]; Cancer Dyspnoea Scale [CDS]), quality of life (Functional Assessment of Cancer Therapy-Lung [FACT-L]), psychological symptoms (Hospital Anxiety and Depression Scale), and activity level (Godin-Shephard Leisure Time Physical Activity Questionnaire). To examine intervention effects, we conducted analysis of covariance and longitudinal mixed effects models. RESULTS: The sample (Agemean = 66.15 years; 55.9% female) primarily included patients with advanced non-small cell lung cancer (85.4%). Compared with usual care, the intervention improved the primary outcome of patient-reported dyspnea on the mMRCDS (difference = -0.33 [95% CI, -0.61 to -0.05]) but not the CDS total score at 8 weeks. Intervention patients also reported less dyspnea on the CDS sense of discomfort subscale (difference = -0.59 [95% CI, -1.16 to -0.01]) and better functional well-being per the FACT-L (difference = 1.39 [95% CI, 0.18 to 2.59]) versus the control group. Study groups did not differ in overall quality of life, psychological symptoms, or activity level at 8 weeks or longitudinally over 24 weeks. CONCLUSION: For patients with advanced lung cancer, a scalable behavioral intervention alleviated the intractable symptom of dyspnea. Further research is needed on ways to enhance intervention effects over the long-term and across additional outcomes.

Effects of Adjuvant Endocrine Therapy-Specific Perceptions on Response to a Behavioral Intervention for Adjuvant Endocrine Therapy Adherence in Patients With Breast Cancer.

PURPOSE: Adjuvant endocrine therapy (AET) is a life-saving medication for patients with hormone-sensitive breast cancer, yet many struggle with adherence, warranting behavioral intervention. In our recent trial, participation in a group cognitive behavioral intervention (STRIDE) for symptom management and adherence was associated with improvements in symptom distress, coping, quality of life, and mood. We now explore whether baseline patient- and medication-specific factors-which may be modifiable by clinician-led discussions-moderated the effect of STRIDE on adherence rates. METHODS: From October 2019 to June 2021, 100 patients with early-stage breast cancer reporting AET-related distress were enrolled and randomly assigned to STRIDE or a medication monitoring (MM) control group. All patients stored their AET in electronic pill bottles to track objective adherence. Patients also self-reported their adherence on the Medication Adherence Report Scale-5 and their perceptions of AET on the Cancer Therapy Satisfaction Questionnaire at baseline. We conducted hierarchical linear modeling to test moderators of intervention effects on objective adherence rates. We report the time × group × moderator effects. RESULTS: Among patients reporting greater perceived difficulties with AET adherence at baseline, STRIDE participants had higher adherence rates over time compared with MM (b = -13.80; SE = 4.56; P < .01). Patients with greater expectations of therapeutic benefit from AET also had improved adherence rates if they were assigned to STRIDE, versus MM (b = 0.25; SE = 0.10; P = .01). Patients who perceived taking AET as convenient and had been taking their AET for less time had higher adherence rates in STRIDE, versus MM. CONCLUSION: The current study identified patient- and medication-specific factors that may augment AET adherence interventions and may be modifiable through clinician-led discussions, such as perceptions of adherence problems, therapeutic efficacy, and convenience of AET.

Design and Development of a Multimodal Digital Intervention (SHIFT App) to Address Sexual Dysfunction in Hematopoietic Stem Cell Transplant (HSCT) Survivors.

BACKGROUND: Hematopoietic stem cell transplant (HSCT) survivors frequently experience persistent sexual dysfunction, which is associated with impaired quality of life (QOL) and increased psychological distress. The lack of availability of clinicians with expertise in sexual health limits the capacity to address sexual health concerns in HSCT survivors. Digital health applications may offer a patient-centered and scalable solution to address sexual health concerns in cancer survivors. The objective of this report is to delineate the iterative process of adapting an in-person sexual health intervention into a self-administered digital application called "Sexual Health and Intimacy Following Transplant (SHIFT)" and the refinement of SHIFT using stakeholder feedback. METHODS: We used a five-step development model to adapt SHIFT that included: 1) implementation of a multimodal bio-psycho-social conceptual framework, 2) development of a comprehensive intervention manual and SHIFT content, 3) translation of the intervention manual into an interactive storyline with a focus on enhancing patient engagement, 4) creation of initial SHIFT wireframes, and 5) refinement of SHIFT through iterative alpha and beta testing. At each step, key stakeholders including HSCT survivors, HSCT clinicians, and experts in sexual health, psychology, and digital health provided iterative feedback. RESULTS: We adapted SHIFT based on our conceptual framework, prior in-person intervention work, and iterative stakeholder feedback in each application development stage. SHIFT incorporates medical information, educational materials, intimacy exercises, and activities to address the multiple etiologies of sexual health concerns in HSCT survivors. SHIFT includes strategies to enhance engagement including gamification, personalization, and incorporation of video from HSCT survivors and clinicians. Based on stakeholder feedback, SHIFT was refined with a focus on inclusivity of gender, sexual orientation, relationship status, and body image concerns. CONCLUSIONS: SHIFT is novel, patient-centered digital application to address sexual dysfunction in HSCT survivors. Iterative feedback from key stakeholders including HSCT survivors guided SHIFT adaptation and refinement, to optimize patient engagement and ensure inclusivity. The final prototype of SHIFT was initially acceptable to key stakeholders and is now under further testing in a pilot randomized trial to assess its feasibility and preliminary efficacy for improving sexual health outcomes in HSCT survivors.

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.

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.

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.

A Digital Therapeutic Application (ePAL) to Manage Pain in Patients With Advanced Cancer: A Randomized Controlled Trial.

BACKGROUND: Patients with advanced cancer often experience immense cancer pain that negatively impacts their quality of life. Interventions to address cancer-related pain are limited. METHODS: We conducted a randomized trial of a digital therapeutic app (ePAL) for patients with advanced cancer receiving care in a specialty palliative care clinic at a tertiary care hospital. Patients were randomized to ePAL or usual care. ePAL included 1) active pain monitoring; 2) artificial intelligence algorithm to triage patient symptoms; and 3) patient education to address barriers to pain management. Participants were instructed to use ePAL over eight weeks. Patient-reported pain symptoms were assessed at baseline, Week-4, and Week-8 (primary endpoint) using the Brief Pain Inventory. Secondary outcomes include pain-related hospitalizations by Week-8. RESULTS: We enrolled 112 patients who were randomly assigned to ePAL (N = 56) or usual care (N = 56). Patients utilized ePAL on average 2.1 times per week to report pain symptoms, and 47.6% reported their pain at least once per week over eight weeks. Patients randomized to ePAL reported lower pain scores at Week-4 (mean: 3.16 vs. 4.28, P = 0.010) and week-8 (mean:2.99 vs. 4.05, P = 0.017), compared to those receiving usual care. Participants randomized to ePAL were less likely to experience a pain-related hospitalization compared to those in the usual care group (7.1% vs. 23.2% P = 0.018) CONCLUSIONS: ePAL was associated with lower patient-reported pain and fewer pain-related hospitalizations compared to usual care in patients with advanced cancer. This study demonstrates the promise of digital therapeutics for improving patients' symptoms while reducing burdensome hospitalizations.

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.

Single Cell Analysis of Proteoforms.

We introduce single cell Proteoform imaging Mass Spectrometry (scPiMS), which realizes the benefit of direct solvent extraction and MS detection of intact proteins from single cells dropcast onto glass slides. Sampling and detection of whole proteoforms by individual ion mass spectrometry enable a scalable approach to single cell proteomics. This new scPiMS platform addresses the throughput bottleneck in single cell proteomics and boosts the cell processing rate by several fold while accessing protein composition with higher coverage.

Dyspnea-Related Dimensions And Self-Efficacy: Associations With Well-Being in Advanced Lung Cancer.

CONTEXT: Dyspnea is a complex, multidimensional symptom comprising sensory-perceptual, affective, and functional domains that commonly persists in patients with lung cancer and impairs mental health and quality of life (QOL). However, data are lacking on how dyspnea's dimensions or self-efficacy to manage dyspnea are associated with patient outcomes. OBJECTIVES: To assess the associations of dyspnea dimensions (dyspnea-related sensory-perceptual experience, affective distress, and functional impact) and dyspnea self-efficacy with depression, anxiety, and QOL in patients with advanced lung cancer reporting dyspnea. METHODS: We conducted a secondary analysis of baseline clinical trial data testing a supportive care intervention for dyspnea. Patients with advanced lung cancer reporting at least moderate dyspnea (≥2 on the Modified Medical Research Council Dyspnea Scale) self-reported dyspnea and patient outcome measures. Hierarchical regressions tested the associations of the dyspnea dimensions with depressive and anxiety symptoms (Hospital Anxiety and Depression Scale) and QOL (Functional Assessment of Cancer Therapy-Lung) while adjusting for variables known to affect these outcomes. RESULTS: The sensory-perceptual experience of dyspnea (effort) was associated with worse depressive symptoms (b = 0.21, P < 0.01) and QOL (b = -0.53, P = 0.01). Dyspnea self-efficacy was associated with improved depressive (b = -1.26, P < 0.01) and anxiety symptoms (b = -1.72, P < 0.01) and QOL (b = 3.66, P < 0.01). The affective and functional dimensions of dyspnea were not associated with the patient outcomes in the final models. CONCLUSIONS: Dyspnea-related sensory-perceptual experience and self-efficacy were associated with mental health and QOL outcomes in patients with lung cancer. Examining the individual contributions of dyspnea's multiple dimensions provides a nuanced understanding of its patient impact.

Using Multiphase Optimization Strategy and Human-Centered Design to Create an Integrated Model of Palliative Care Skills in Home-Based Physical Therapy for Advanced Heart Failure.

Background: Many older adults with advanced heart failure receive home health rehabilitation after hospitalization. Yet, integration of palliative care skills into rehabilitation is limited. Objective: Describe using the Multiphase Optimization Strategy (MOST) framework with human-centered design principles to engage clinical partners in the Preparation phase of palliative physical therapy intervention development. Design: We convened a home-based physical therapy advisory team (four clinicians, three clinical leaders) to identify physical therapist needs and preferences for incorporating palliative care skills in rehabilitation and design an intervention prototype. Results: Between 2022 and 2023, we held five advisory team meetings. Initial feedback on palliative care skill preferences and training needs directly informed refinement of our conceptual model and skills in the intervention prototype. Later feedback focused on reviewing and revising intervention content, delivery strategy, and training considerations. Conclusion: Incorporating human-centered design principles within the MOST provided a useful framework to partner with clinical colleagues in intervention design.

Group Coping Intervention in Patients With Chronic Graft-Versus-Host Disease: A Pilot Randomized Clinical Trial.

BACKGROUND: More than half the long-term survivors of allogeneic hematopoietic cell transplantation develop chronic graft-versus-host disease (GVHD), a debilitating inflammatory syndrome. Supportive interventions to assist survivors in coping with chronic GVHD are critically needed. PATIENTS AND METHODS: We conducted a pilot randomized clinical trial of a multidisciplinary group intervention (Horizons Program; n=39) versus minimally enhanced usual care (n=41) for patients with moderate or severe chronic GVHD. Horizons participants received 8 weekly sessions about GVHD and coping co-led by a transplant clinician and a behavioral health expert via a secure videoconferencing platform. Participants completed the following surveys before randomization, at 10 weeks, and at 18 weeks: Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT) for quality of life (QoL), Lee Symptom Scale for symptom burden, and Hospital Anxiety and Depression Scale-Depression Symptoms (HADS) for mood. The primary endpoint was feasibility (≥50% enrollment, ≥80% attendance in half the sessions for the Horizons arm only, and ≥80% retention). We also explored preliminary efficacy of the Horizons intervention on changes in patient-reported outcomes with linear mixed effects models and estimates of effect size at 10 weeks. RESULTS: We enrolled and registered 80 (67.2%) of 119 eligible patients (mean age, 62 years; 48.8% female). Of the participants in the Horizons Program, 84.6% attended at least half the sessions. Of registered participants, 91.3% completed assessment follow-ups (Horizons, 35/39 [89.7%]; minimally enhanced usual care, 38/41 [92.7%]). Horizons participants reported improvements in QoL (b = 2.24; d=0.53), anxiety symptoms (b = -0.10; d=0.34), and depression symptoms (b = -0.71; d=0.44) compared with participants who received minimally enhanced usual care. CONCLUSIONS: Participation in a multidisciplinary group intervention study was feasible for patients with chronic GVHD, with promising signals for improving QoL and mood. A full-scale efficacy trial is needed to confirm effects on patient-reported outcomes.

Concurrent factors associated with adherence to adjuvant endocrine therapy among women with non-metastatic breast cancer.

PURPOSE: Adjuvant endocrine therapy (AET) reduces breast cancer morbidity and mortality, yet women often report suboptimal adherence. Though correlates of AET adherence are well-documented, few studies examine the relative importance of multi-level factors associated with adherence. The aim of this study was to identify factors most strongly associated with AET adherence in women with breast cancer. METHODS: Between 10/2019 and 6/2021, women (N = 100) with non-metastatic, hormone receptor-positive breast cancer, taking AET who reported AET-related distress enrolled into a clinical trial. Participants completed baseline measures, including the Medication Adherence Rating Scale-5, sociodemographics, and validated measures of anxiety, depression, medication-taking self-efficacy, social support, and treatment satisfaction. We created a latent factor and tested associations between sociodemographic, medical, and psychosocial characteristics and adherence. Associated predictors (p < .10) were entered into a structural model, which was corroborated via multivariate regression modeling. RESULTS: A four-indicator latent adherence factor demonstrated good model fit. Participants (Mage = 56.1 years, 91% White) who were unemployed (B = 0.27, SE = 0.13, p = .046) and reported greater treatment convenience (B = 0.01, SE = 0.01, p = .046) reported greater adherence. Scores of participants who reported greater medication-taking self-efficacy (p = .097) and social support (p = .062) approached better adherence. Greater medication-taking self-efficacy (B = 0.08, SE = 0.02, p < .001) and being unemployed (B = 0.28, SE = .14, p = .042) were most strongly associated with greater adherence, independent of other predictors. Multivariate modeling confirmed similar findings. CONCLUSIONS: Medication-taking self-efficacy and employment status were associated with AET adherence above other related factors. IMPLICATIONS FOR CANCER SURVIVORS: Enhancing patients' confidence in their ability to take AET for breast cancer may represent an important intervention target to boost adherence.

Identification of patient subgroups who benefit from a behavioral intervention to improve adjuvant endocrine therapy adherence: a randomized-controlled trial.

PURPOSE: Adjuvant endocrine therapy (AET) reduces breast cancer morbidity and mortality; however, adherence is suboptimal. Interventions exist, yet few have improved adherence. Patient characteristics may alter uptake of an intervention to boost adherence. We examined moderators of the effect of a virtual intervention (STRIDE; #NCT03837496) on AET adherence after breast cancer. METHODS: At a large academic medical center, patients taking AET (N = 100; Mage = 56.1, 91% White) were randomized to receive STRIDE versus medication monitoring. All stored their medication in digital pill bottles (MEMS Caps) which captured objective adherence. Participants self-reported adherence (Medication Adherence Report Scale) at 12 weeks post-baseline. Moderators included age, anxiety, and depressive symptoms (Hospital Anxiety and Depression Scale), AET-related symptom distress (Breast Cancer Prevention Trial Symptom Scale), and AET-specific concerns (Beliefs about Medications Questionnaire). We used hierarchical linear modeling (time × condition × moderator) and multiple regression (condition × moderator) to test the interaction effects on adherence. RESULTS: Age (B = 0.05, SE = 0.02, p = 0.003) and AET-related symptom distress (B = -0.04, SE = 0.02, p = 0.02) moderated condition effect on self-reported adherence while anxiety (B = -1.20, SE = 0.53, p = 0.03) and depressive symptoms (B = -1.65, SE = 0.65, p = 0.01) moderated objective adherence effects. AET-specific concerns approached significance (B = 0.91, SE = 0.57, p = 0.12). Participants who received STRIDE and were older or presented with lower anxiety and depressive symptoms or AET-related symptom distress exhibited improved adherence. Post hoc analyses revealed high correlations among most moderators. CONCLUSIONS: A subgroup of patients who received STRIDE exhibited improvements in AET adherence. The interrelatedness of moderators suggests an underlying profile of patients with lower symptom burden who benefitted most from the intervention. STUDY REGISTRATION: NCT03837496.

Protocol for multi-site randomized trial of inpatient palliative care for patients with hematologic malignancies undergoing hematopoietic stem cell transplantation.

BACKGROUND: Patients with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT) commonly experience debilitating physical and psychological symptoms during a 3-4-week-hospitalization. During hospitalization, caregivers (i.e., family and friends) also endure immense emotional stress as they witness their loved one struggle with HSCT toxicities. Yet interventions to improve quality of life (QOL) and reduce psychological distress during HSCT are limited. METHODS: We are conducting a multi-site randomized controlled trial of inpatient integrated palliative and transplant care versus usual care in 360 patients hospitalized for HSCT and their caregivers at three academic centers. Intervention participants meet with a palliative care clinician at least twice weekly during the HSCT hospitalization to address their physical and psychological symptoms. Patients assigned to usual care receive all supportive care measures provided by the HSCT team and could be seen by palliative care upon request. We assess patient QOL (Functional Assessment of Cancer Therapy (FACT) - Bone Marrow Transplant), depression and anxiety symptoms (Hospital Anxiety and Depression Scale), post-traumatic stress (PTSD) symptoms (PTSD checklist), symptom burden (Edmonton Symptom Assessment Scale), and fatigue (FACT-Fatigue) as well as caregiver-reported outcomes at baseline, 2 weeks, 3-months, 6-months, and 12-months post-HSCT. The primary endpoint is to compare QOL at week-2 during HSCT hospitalization between the two groups when patients typically experience their QOL nadir during HSCT. CONCLUSIONS: This multi-site trial will define the role of palliative care for improving QOL and care for patients with hematologic malignancies undergoing HSCT and their caregivers.

Managing Symptom Distress: Key Factors for Patients on Adjuvant Endocrine Therapy for Breast Cancer.

CONTEXT: Patients with breast cancer taking adjuvant endocrine therapy (AET) experience significant symptoms impacting mood, quality of life (QOL), and AET adherence and satisfaction. OBJECTIVES: The aim of this study was to examine the extent to which coping ability and self-efficacy for symptom management moderate the relationships between patients' symptom distress and their mood, QOL, and AET adherence and satisfaction. METHODS: As part of a randomized controlled trial, participants completed baseline measures including: sociodemographics, symptom distress (breast cancer prevention trial symptom checklist), coping skills (measure of current status), self-efficacy (self-efficacy for managing symptoms), anxiety and depression (hospital anxiety and depression scale), QOL (functional assessment of cancer therapy - general), AET adherence (medication adherence report scale), and AET satisfaction (cancer therapy satisfaction questionnaire). We conducted moderated regression analyses to examine whether coping and self-efficacy moderated the associations of symptom distress with baseline measures. RESULTS: Coping skills moderated the associations of symptom distress with depression and QOL. Among those with lower coping, higher symptom distress was associated with worse depression symptoms (p=.04) and worse QOL (p < 0.001). Self-efficacy moderated the associations of symptom distress with depression symptoms and AET adherence and satisfaction. Among those with higher self-efficacy, higher symptom distress was associated with worse depression symptoms (p < 0.001), worse AET adherence (p < 0.001), and less AET satisfaction (p = 0.01). CONCLUSION: Coping skills may buffer the effect of AET symptom distress. Findings indicate the relationship between symptom distress and self-efficacy is more nuanced and requires further research to better understand.

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.

Advancing Intact Protein Quantitation with Updated Deconvolution Routines.

Analysis of intact proteins by mass spectrometry enables direct quantitation of the specific proteoforms present in a sample and is an increasingly important tool for biopharmaceutical and academic research. Interpreting and quantifying intact protein species from mass spectra typically involves many challenges including mass deconvolution and peak processing as well as determining optimal spectral averaging parameters and matching masses to theoretical proteoforms. Each of these steps can present informatic hurdles, as parameters often need to be tailored specifically to the data sets. To reduce intact mass deconvolution data analysis burdens, we built upon the widely used "sliding window" mass deconvolution technique with several additional concepts. First, we found that how spectra are averaged and the overlap in spectral windows can be tuned to favor either sensitivity or speed. A multiple window averaging approach was found to be the most effective way to increase mass detection and yielded a >2-fold increase in the number of masses detected. We also developed a targeted feature-finding routine that boosted sensitivity by >2-fold, decreased coefficient of variation across replicates by 50%, and increased the quality of mass elution profiles through 3-fold more detected time points. Lastly, we furthered existing approaches for annotating detected masses with potential proteoforms through spectral fitting for possible proteoform family modifications and network viewing. These proteoform annotation approaches ultimately produced a more accurate way of finding related, but previously unknown proteoforms from intact mass-only data. Together, these quantitation workflow improvements advance the information obtainable from intact protein mass spectrometry analyses.

Orbitrap Mass Spectrometry and High-Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) Enable the in-Depth Analysis of Human Serum Proteoforms.

Blood serum and plasma are arguably the most commonly analyzed clinical samples, with dozens of proteins serving as validated biomarkers for various human diseases. Top-down proteomics may provide additional insights into disease etiopathogenesis since this approach focuses on protein forms, or proteoforms, originally circulating in blood, potentially providing access to information about relevant post-translational modifications, truncations, single amino acid substitutions, and many other sources of protein variation. However, the vast majority of proteomic studies on serum and plasma are carried out using peptide-centric, bottom-up approaches that cannot recapitulate the original proteoform content of samples. Clinical laboratories have been slow to adopt top-down analysis, also due to higher sample handling requirements. In this study, we describe a straightforward protocol for intact proteoform sample preparation based on the depletion of albumin and immunoglobulins, followed by simplified protein fractionation via polyacrylamide gel electrophoresis. After molecular weight-based fractionation, we supplemented the traditional liquid chromatography-tandem mass spectrometry (LC-MS2) data acquisition with high-field asymmetric waveform ion mobility spectrometry (FAIMS) to further simplify serum proteoform mixtures. This LC-FAIMS-MS2 method led to the identification of over 1000 serum proteoforms < 30 kDa, outperforming traditional LC-MS2 data acquisition and more than doubling the number of proteoforms identified in previous studies.