Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is lethal in 88% of patients1, yet harbours mutation-derived T cell neoantigens that are suitable for vaccines 2,3. Here in a phase I trial of adjuvant autogene cevumeran, an individualized neoantigen vaccine based on uridine mRNA-lipoplex nanoparticles, we synthesized mRNA neoantigen vaccines in real time from surgically resected PDAC tumours. After surgery, we sequentially administered atezolizumab (an anti-PD-L1 immunotherapy), autogene cevumeran (a maximum of 20 neoantigens per patient) and a modified version of a four-drug chemotherapy regimen (mFOLFIRINOX, comprising folinic acid, fluorouracil, irinotecan and oxaliplatin). The end points included vaccine-induced neoantigen-specific T cells by high-threshold assays, 18-month recurrence-free survival and oncologic feasibility. We treated 16 patients with atezolizumab and autogene cevumeran, then 15 patients with mFOLFIRINOX. Autogene cevumeran was administered within 3 days of benchmarked times, was tolerable and induced de novo high-magnitude neoantigen-specific T cells in 8 out of 16 patients, with half targeting more than one vaccine neoantigen. Using a new mathematical strategy to track T cell clones (CloneTrack) and functional assays, we found that vaccine-expanded T cells comprised up to 10% of all blood T cells, re-expanded with a vaccine booster and included long-lived polyfunctional neoantigen-specific effector CD8+ T cells. At 18-month median follow-up, patients with vaccine-expanded T cells (responders) had a longer median recurrence-free survival (not reached) compared with patients without vaccine-expanded T cells (non-responders; 13.4 months, P = 0.003). Differences in the immune fitness of the patients did not confound this correlation, as responders and non-responders mounted equivalent immunity to a concurrent unrelated mRNA vaccine against SARS-CoV-2. Thus, adjuvant atezolizumab, autogene cevumeran and mFOLFIRINOX induces substantial T cell activity that may correlate with delayed PDAC recurrence.

Development and perception of surgery-specific goals of care discussions in the preoperative setting: A learning pilot.

BACKGROUND: Goals of care discussions are infrequently documented in the preoperative period. Furthermore, documentation does not consistently address what matters most to patients, although patient values (PV) are central to person-centered care. METHODS: A multidisciplinary working group was formed. An electronic note comprised of (1) topics of discussion, (2) PV, and (3) advance care planning (ACP), was created and embedded into existing note templates for Gynecologic Surgical Oncology. Surgeons and advanced practice providers (APPs) were educated to conduct and document these conversations in preoperative clinic for patients undergoing cancer surgery for a pilot period. Data were collected regarding usage of the template. Focus groups with surgeons, APPs, and patients were conducted. Qualitative analysis was performed on transcripts. RESULTS: During the pilot, 7 surgeon/APP teams utilized the template on a total of 55 notes. Average number of notes completed per surgeon was 7.8 (SD 8.5). Forty-six notes (84%) included topics of discussion, 15 (27%) included PV, 4 (7%) included ACP. Qualitative analysis of focus group transcripts revealed that clinicians and patients perceived the initiative to be useful and important, although implementation barriers were identified. CONCLUSION: Creating a surgery-specific GOC template is feasible. Iterative revisions are needed to increase utility in clinic workflows.

Integrating evidence-based communication principles into routine cancer care.

PURPOSE: The global incidence of cancer and available cancer-directed therapy options is increasing rapidly, presenting patients and clinicians with more complex treatment decisions than ever before. Despite the dissemination of evidence-based communication training tools and programs, clinicians cite barriers to employing effective communication in cancer care (e.g., discomfort of sharing serious news, concern about resource constraints to meet stated needs). We present two composite cases with significant communication challenges to guide clinicians through an application of evidence-based approaches to achieve quality communication. METHODS: Composite cases, communication skills blueprint, and visual conceptualization. RESULTS: High-stakes circumstances in each case are described, including end-of-life planning, advanced pediatric illness, strong emotions, and health inequities. Three overarching communication approaches are discussed: (1) content selection and delivery; (2) rapport development; and (3) empathic connection. The key takeaways following each case provide succinct summaries of challenges encountered and approaches used. A communication blueprint from the Memorial Sloan Kettering Cancer Center Communication Skills Training Program and Research Laboratory has been adapted and is comprised of strategies, skills, process tasks, and sample talking points. A visually concise tool - the Communication Blueprint Traffic Circle - illustrates these concepts and demonstrates the iterative, holistic, and agile considerations inherent to effective communication. CONCLUSION: Evidence-based communication is foundational to person-centeredness, associated with improved clinician and patient/caregiver outcomes, and can be integrated throughout routine oncology care. When used by clinicians, evidence-based communication can improve patient and caregiver experiences and assist in ensuring goal-concordant cancer care delivery.

The Third Annual US Celebration of World Hospice and Palliative Care Day: A virtual coming together to unify the global palliative care community.

OBJECTIVES: On 3-4 October 2022, the Memorial Sloan Kettering Cancer Center Supportive Care Service and Department of Psychiatry and Behavioral Sciences hosted the Third Annual United States (US) Celebration of World Hospice and Palliative Care Day (WHPCD). The purpose of this article is to reflect on the event within the broader context of the international WHPCD theme: "healing hearts and communities." We describe lessons learned in anticipation of the fourth annual conference to be held on 3-4 October 2023. METHODS: Description of the third annual event, conference planning team reflection, and attendee evaluation responses. RESULTS: The Worldwide Hospice Palliative Care Alliance launched WHPCD in 2005 as an annual unified day of action to celebrate and support hospice and palliative care globally. Since 2020, the conference has attracted an increasing number of attendees from around the world. Two primary aims continue to guide the event: community building and wisdom sharing. Fifty-two interprofessional palliative care experts, advocates, patients, and caregivers provided 13 unique interactive sessions. Four hundred and fifty-eight multidisciplinary registrants from at least 17 countries joined the program. Free registration for colleagues in low- and middle-income countries, students and trainees, and individuals experiencing financial hardship remains a cornerstone of inclusion and equitable access to the event. SIGNIFICANCE OF RESULTS: The US WHPCD celebration provides a virtual platform that offers opportunities for scientific dissemination and collective reflection on hospice and palliative care delivery amid significant local and global changes in clinical practice, research, policy and advocacy, and population health. We remain committed to ensuring an internationally relevant, culturally diverse, and multidisciplinary agenda that will continue to draw increased participation worldwide during future annual events.

Goals of care documentation by medical oncologists and oncology patient end-of-life care outcomes.

BACKGROUND: Goals of care (GOC) documentation is important but underused. We aimed to improve oncologist GOC documentation and end-of-life (EOL) care. METHODS: In April 2020, our cancer center launched a GOC note template, including optional fields for documenting discussion with the patient about: cancer natural history, goals, and/or EOL (resuscitation preferences, hospice receptivity). Associations between GOC notes and EOL care were evaluated. RESULTS: Among 1721 patients dying between June 1, 2020 and June 30, 2021, median days from first GOC note (± with documentation of EOL discussion) to death was 92, whereas a GOC note including EOL discussion ("GOC EOL note"), specifically, was 31. Patients with a first GOC note >60 days before death spent fewer days inpatient (6.7 vs 10.6 days, p < .001). Among patients with GOC EOL notes, those with such documentation >30 days before death had fewer inpatient (5 vs 11, p < .001) and intensive care unit days (0.5 vs 1.5, p < .001), more hospice referrals (57% vs 44%, p = .003), and less chemotherapy ≤14 days before death (6% vs 11%, p = .010). Of 925 admissions of patients dying within ≤30 days, those with GOC EOL notes were shorter (7 vs 9 days, p = .013) but not associated with more hospice discharge (30% vs 25%, p = .163). Oncologist (vs nononcologist) GOC documentation and earlier documentation of EOL discussion were associated in subset analyses with less inpatient care and more hospice referrals. CONCLUSIONS: Documentation of GOC, including EOL discussions, is associated with favorable performance on accepted indicators of quality EOL care.

Circulating tumor and invasive cell expression profiling predicts effective therapy in pancreatic cancer.

BACKGROUND: Pancreatic adenocarcinoma (PDAC) remains a refractory disease; however, modern cytotoxic chemotherapeutics can induce tumor regression and extend life. A blood-based, pharmacogenomic, chemosensitivity assay using gene expression profiling of circulating tumor and invasive cells (CTICs) to predict treatment response was previously developed. The combination regimen of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) and gemcitabine/nab-paclitaxel (G/nab-P) are established frontline approaches for treating advanced PDAC; however, there are no validated biomarkers for treatment selection. A similar unmet need exists for choosing second-line therapy. METHODS: The chemosensitivity assay was evaluated in metastatic PDAC patients presenting for frontline treatment. A prospective study enrolled patients (n = 70) before receiving either FOLFIRINOX or G/nab-P at a 1:1 ratio. Six milliliters of peripheral blood was collected at baseline and at time of disease progression. CTICs were isolated, gene-expression profiling was performed, and the assay was used to predict effective and ineffective chemotherapeutic agents. Treating physicians were blinded to the assay prediction results. RESULTS: Patients receiving an effective regimen as predicted by the chemosensitivity assay experienced significantly longer median progression-free survival (mPFS; 7.8 months vs. 4.2 months; hazard ratio [HR], 0.35; p = .0002) and median overall survival (mOS; 21.0 months vs. 9.7 months; HR, 0.40; p = .005), compared with an ineffective regimen. Assay prediction for effective second-line therapy was explored. The entire study cohort experienced favorable outcomes compared with historical controls, 7.1-month mPFS and 12.3-month mOS. CONCLUSIONS: Chemosensitivity assay profiling is a promising tool for guiding therapy in advanced PDAC. Further prospective validation is under way (clinicaltrials.gov NCT03033927).

Reconciling the prospect of disease progression with goals and expectations: Development and validation of a measurement model in advanced cancer.

OBJECTIVE: Among patients living with advanced, life-limiting illness, reconciling the prospect of disease progression with future goals and expectations is a key psychological task, integral to treatment decision-making and emotional well-being. To date, this psychological process remains poorly understood with no available measurement tools. The present paper develops and validates a measurement model for operationalizing this psychological process. METHODS: In Phase 1, concept elicitation interviews were conducted among Stage IV lung, gastrointestinal, and gynecologic cancer patients, their caregivers, and experts (N = 19), to further develop our conceptual framework centered on assimilation and accommodation coping. In Phase 2, draft self-report items of common assimilation and accommodation coping strategies were evaluated via patient cognitive interviews (N = 11). RESULTS: Phase 1 interviews identified several coping strategies, some of which aimed to reduce the perceived likelihood of disease progression (assimilation), and others aimed to integrate the likelihood into new goals and expectations (accommodation). The coping strategies appeared to manifest in patients' daily lives, and integrally related to their emotional well-being and how they think about treatments. Phase 2 cognitive interviews identified items to remove and modify, resulting in a 31-item measure assessing 10 assimilation and accommodation coping strategies. CONCLUSIONS: The present work derived a content-valid measure of the psychological process by which patients reconcile the prospect of disease progression with their goals and expectations. Further psychometric validation and use of the scale could identify intervention targets for enhancing patient decision-making and well-being.

Navigating a newly diagnosed cancer through clinician-facilitated discussions of health-related patient values: a qualitative analysis.

BACKGROUND: Advance care planning, the process through which patient values and goals are explored and documented, is a core quality indicator in cancer care. However, patient values are predominantly elicited at the end of life; patient values earlier in serious illness are not clearly delineated. The objective of this analysis is to assess the content of patient-verified summaries of health-related values among newly diagnosed cancer outpatients in order to develop a theoretical framework to guide future values discussions and optimize person-centered oncologic care. METHODS: Values summaries among patients with gastrointestinal (GI) cancers or myelodysplastic syndrome (MDS) were extracted from the medical record. Modified grounded theory analysis included interdisciplinary team coding of values summaries to identify key domains; code categorization; and identification of thematic constructs during successive consensus meetings. A final round of coding stratified themes by disease type. RESULTS: Analysis of 128 patient values summary documents from 67 patients (gastrointestinal [GI] cancers, n = 49; myelodysplastic syndrome [MDS], n = 18) generated 115 codes across 12 categories. Resultant themes demonstrated patients' focus on retaining agency, personhood and interpersonal connection amidst practical and existential disruption caused by cancer. Themes coalesced into a theoretical framework with 5 sequenced constructs beginning with the cancer diagnosis, leading to 3 nesting constructs of individual identity (character), interpersonal (communication) preferences and needs, and social identity (connection), signifying sources of meaning and fulfillment. Values differences between GI cancer and MDS patients-including greater focus on normalcy, prognosis, and maintaining professional life among GI patients-reflected the distinct therapeutic options and prognoses across these disease groups. CONCLUSIONS: Patient values reflect goals of meaning-making and fulfillment through individual agency and interpersonal supports in the setting of a newly diagnosed cancer. Early, nurse-led values discussions provide important and patient-specific data that are informative and likely actionable by clinicians in the delivery of person-centered care. Values can also facilitate discussions between patients and families and clarify patient preferences.

The 2nd Annual US Celebration of World Hospice and Palliative Care Day: A virtual coming together to support equity in palliative care access.

OBJECTIVE: On October 5-6, 2021, the Memorial Sloan Kettering Cancer Center Supportive Care Service and Department of Psychiatry and Behavioral Sciences hosted the 2nd Annual United States (US) Celebration of World Hospice and Palliative Care Day (WHPCD). The purpose of this article is to describe the event within the broader context of the international WHPCD theme: "Leave No One Behind - Equity in Access to Palliative Care." We reflect on lessons learned in anticipation of the 3rd annual conference to be held October 3-4, 2022. METHODS: Description of the 2nd annual event, conference planning team reflection, and attendee evaluation responses. RESULTS: The Worldwide Hospice Palliative Care Alliance launched WHPCD in 2005 as an annual unified day of action to celebrate and support hospice and palliative care around the world. The 2021 US-based innovative virtual conference featured 37 interprofessional hospice and palliative care specialists and patient and family caregiver speakers across 11 diverse sessions with a focus on health equity and COVID-19 considerations. Two primary aims continue to guide the event: community building and wisdom sharing at the intersection of art and science. 278 registrants from at least 14 countries and 21 different states across the US joined the program, which served as a global debriefing for hospice and palliative care workers from diverse settings, contexts, and disciplines. SIGNIFICANCE OF RESULTS: The US WHPCD Celebration creates a virtual coming together for collective reflection on hospice and palliative care delivery amid vast changes in clinical practice, research, and policy, both locally and globally. In addition, our goal to ensure an internationally relevant, culturally inclusive, and multidisciplinary agenda will continue to draw increased participation worldwide during future annual events.

Prognostic value of the Memorial Sloan Kettering Prognostic Score in metastatic pancreatic adenocarcinoma.

BACKGROUND: The Memorial Sloan Kettering Prognostic Score (MPS), a composite of the neutrophil-lymphocyte ratio (NLR) and albumin, is an objective prognostic tool created as a more readily available alternative to the Glasgow Prognostic Score. A prior analysis of patients with metastatic pancreatic adenocarcinoma (mPDAC) suggested that the MPS may predict survival, although it did not control for clinically relevant factors. METHODS: MPS scores were calculated for patients with mPDAC treated at Memorial Sloan Kettering Cancer Center from January 1, 2011, to December 31, 2014. An MPS scale of 0 to 2 was used: 0 for an albumin level ≥ 4 g/dL and an NLR ≤ 4 g/dL, 1 for either an albumin level < 4 g/dL or an NLR > 4 g/dL, and 2 for an albumin level < 4 g/dL and an NLR > 4 g/dL. Performance status, antineoplastic therapy, presence of thromboembolism (TE), radiation therapy, and metastatic sites were also analyzed. The associations with overall survival were examined with time-dependent Cox proportional hazards regression analyses. RESULTS: A multivariate model revealed that higher MPS scores at diagnosis (hazard ratio for MPS of 2 vs MPS of 0, 1.41; 95% confidence interval, 1.13-1.76), liver metastases, radiation therapy, hospital admissions, TE, and performance status were associated with worse overall survival. The median overall survival for patients with MPS scores of 0, 1, and 2 were 12.9, 9.0, and 5.4 months, respectively. CONCLUSIONS: The MPS, an easily calculated composite of the NLR and albumin, is an objective tool that may predict survival in mPDAC independently of performance status, disease characteristics, and cancer therapy. LAY SUMMARY: The Memorial Sloan Kettering Prognostic Score (MPS) is a new scoring system that incorporates markers of inflammation found in individuals' blood at the diagnosis of metastatic pancreatic cancer. Data suggest that the MPS may help to determine prognosis.

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.

A Novel Patient Values Tab for the Electronic Health Record: A User-Centered Design Approach.

BACKGROUND: The COVID-19 pandemic has shined a harsh light on a critical deficiency in our health care system: our inability to access important information about patients' values, goals, and preferences in the electronic health record (EHR). At Memorial Sloan Kettering Cancer Center (MSK), we have integrated and systematized health-related values discussions led by oncology nurses for newly diagnosed cancer patients as part of routine comprehensive cancer care. Such conversations include not only the patient's wishes for care at the end of life but also more holistic personal values, including sources of strength, concerns, hopes, and their definition of an acceptable quality of life. In addition, health care providers use a structured template to document their discussions of patient goals of care. OBJECTIVE: To provide ready access to key information about the patient as a person with individual values, goals, and preferences, we undertook the creation of the Patient Values Tab in our center's EHR to display this information in a single, central location. Here, we describe the interprofessional, interdisciplinary, iterative process and user-centered design methodology that we applied to build this novel functionality as well as our initial implementation experience and plans for evaluation. METHODS: We first convened a working group of experts from multiple departments, including medical oncology, health informatics, information systems, nursing informatics, nursing education, and supportive care, and a user experience designer. We conducted in-depth, semistructured, audiorecorded interviews of over 100 key stakeholders. The working group sought consensus on the tab's main content, homing in on high-priority areas identified by the stakeholders. The core content was mapped to various EHR data sources. We established a set of high-level design principles to guide our process. Our user experience designer then created wireframes of the tab design. The designer conducted usability testing with physicians, nurses, and other health professionals. Data validation testing was conducted. RESULTS: We have already deployed the Patient Values Tab to a pilot sample of users in the MSK Gastrointestinal Medical Oncology Service, including physicians, advanced practice providers, nurses, and administrative staff. We have early evidence of the positive impact of this EHR innovation. Audit logs show increasing use. Many of the initial user comments have been enthusiastically positive, while others have provided constructive suggestions for additional tab refinements with respect to format and content. CONCLUSIONS: It is our challenge and obligation to enrich the EHR with information about the patient as a person. Realization of this capability is a pressing public health need requiring the collaboration of technological experts with a broad range of clinical leaders, users, patients, and families to achieve solutions that are both principled and practical. Our new Patient Values Tab represents a step forward in this important direction.

The inaugural United States World Hospice and Palliative Care Day Celebration: A virtual coming together.

OBJECTIVE: On October 10, 2020, the Memorial Sloan Kettering Cancer Center Supportive Care Service hosted their first-ever United States (US) World Hospice and Palliative Care Day (WHPCD) Celebration. The purpose of this article is to describe the US inaugural event in alignment with the broader goals of WHPCD and provide lessons learned in anticipation of the second annual conference to be held on October 5-6, 2021. METHODS: Description of the inaugural event in the context of COVID-19 and WHPCD, co-planning conference team reflection, and attendee survey responses. RESULTS: The Worldwide Hospice Palliative Care Alliance initially launched WHPCD in 2005 as an annual unified day of action to celebrate and support hospice and palliative care around the world. The US-based innovative virtual conference featured 23 interprofessional hospice and palliative care specialists and patient and family caregiver speakers across nine diverse sessions addressing priorities at the intersection of COVID-19, social injustice, and the global burden of serious health-related suffering. Two primary aims guided the event: community building and wisdom sharing. Nearly 270 registrants from at least 16 countries and one dozen states across the US joined the free program focused on both personal and professional development. SIGNIFICANCE OF RESULTS: Unlike many other academic conferences and professional gatherings that were relegated to online forums due to pandemic-related restrictions, the US WHPCD Celebration was intentionally established to create a virtual coming together for collective reflection on the barriers and facilitators of palliative care delivery amid vast societal change. The goal to ensure a globally relevant and culturally inclusive agenda will continue to draw increased participation at an international level during future annual events. Finally, the transparent and respectful sharing of palliative care team experiences in the year preceding the conference established a safe environment for both individual expression and scholarly discussion.

"My doctor says the cancer is worse, but I believe in miracles"-When religious belief in miracles diminishes the impact of news of cancer progression on change in prognostic understanding.

BACKGROUND: News of cancer progression is critical to setting accurate prognostic understanding, which guides patients' treatment decision making. This study examines whether religious belief in miracles modifies the effect of receiving news of cancer progression on change in prognostic understanding. METHODS: In a multisite, prospective cohort study, 158 patients with advanced cancer, whom oncologists expected to die within 6 months, were assessed before and after the visit at which scan results were discussed. Before the visit, religious belief in miracles was assessed; after the visit, patients indicated what scan results they had received (cancer was worse vs cancer was stable, better, or other). Before and after the visit, prognostic understanding was assessed, and a change score was computed. RESULTS: Approximately 78% of the participants (n = 123) reported at least some belief in miracles, with almost half (n = 73) endorsing the strongest possible belief. A significant interaction effect emerged between receiving news of cancer progression and belief in miracles in predicting change in prognostic understanding (b = -0.18, P = .04). Receiving news of cancer progression was associated with improvement in the accuracy of prognostic understanding among patients with weak belief in miracles (b = 0.67, P = .007); however, among patients with moderate to strong belief in miracles, news of cancer progression was unrelated to change in prognostic understanding (b = 0.08, P = .64). CONCLUSIONS: Religious belief in miracles was highly prevalent and diminished the impact of receiving news of cancer progression on prognostic understanding. Assessing patients' beliefs in miracles may help to optimize the effectiveness of "bad news" scan result discussions.

Outcomes of ICU Admission of Patients With Progressive Metastatic Gastrointestinal Cancer.

BACKGROUND: Data on the outcomes of intensive care unit (ICU) admissions for patients with advanced incurable chemoresistant solid tumor malignancies, and the benefits of subsequent/post-ICU anticancer treatments are limited but have end-of-life and ethical implications. METHODS: An institutional database was queried to identify patients of the gastrointestinal (GI) medical oncology service of Memorial Sloan Kettering Cancer Center with ≥1 ICU admission during 2014. Records were reviewed for evidence of cancer control from cancer treatment after the ICU admission. RESULTS: Twenty-eight patients who had progressed beyond at least first-line chemotherapy for metastatic GI adenocarcinoma were admitted to the ICU for sequelae of progressive clinical deterioration. The most frequent reasons for ICU admission were sepsis (39%) and acute respiratory failure (29%). Ten patients died in the ICU, 3 died during the same hospitalization after ICU discharge, and 15 were discharged from the hospital. Of these 15, the median survival from hospital discharge was 2.2 months and 6 received further chemotherapy but with no evidence of clinical benefit. Of these 6, 3 lived over 5 months but the treatment of 5 entailed recycling of previously ineffective chemotherapy agents (3) or those originally used in the adjuvant setting (2). Two of these patients received liver-directed therapy without benefit. CONCLUSIONS: Admissions to the ICU in this cancer population were associated with high morbidity and mortality and did not result in benefit from subsequent cancer treatment. These data can be used to help establish realistic expectations and care goals in previously treated patients having metastatic GI cancer with clinical deterioration.

A mixed methods analysis of patients' advance care planning values in outpatient oncology: Person-Centered Oncologic Care and Choices (P-COCC).

PURPOSE: Person-Centered Oncologic Care and Choices (P-COCC) combines an advance care planning (ACP) value-focused patient interview with a care goal video decision aid. Our randomized study showed that P-COCC was acceptable but increased participant distress, compared with video-alone and usual care study arms. This mixed methods approach explores the ACP values in the P-COCC arm and their relationship to the distress phenomenon. METHODS: Qualitative thematic analysis of the 46 audio-recorded P-COCC interview transcripts with advanced gastrointestinal cancer patients was performed by multiple reviewers. Quantitative (Likert scale) changes in ACP values were compared across study arms. ACP themes and value change were analyzed in participants with increased distress. RESULTS: Transcript analysis resulted in thematic saturation and identified eight distinct themes on ACP values relating to end-of-life wishes, communication needs, and psychosocial supports. Of 98 participants (33 P-COCC, 43 videos, 22 usual care) who completed the change in value measure, there was no difference detected with P-COCC compared with either video (p = 0.052) or usual care (p = 0.105) arms alone, but P-COCC led to a frequency distribution of more change in personal values compared with the other study arms combined (p = 0.043). Among the subset of P-COCC participants with increased distress, there was no statistical relationship with change in values. CONCLUSIONS: The ACP paradigm P-COCC both informs and supports patients in individualized, value-based decision-making. Distress is not associated with changes in ACP values and may be a necessary, at least transient, byproduct of discussing sensitive but pertinent topics about end-of-life medical care.

Pancreatic cancer-A disease in need: Optimizing and integrating supportive care.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy that continues to be challenging to treat. PDAC has the lowest 5-year relative survival rate compared with all other solid tumor malignancies and is expected to become the second-leading cause of cancer-related death in the United States by 2030. Given the high mortality, there is an increasing role for concurrent anticancer and supportive care in the management of patients with PDAC with the aims of maximizing length of life, quality of life, and symptom control. Emerging trends in supportive care that can be integrated into the clinical management of patients with PDAC include standardized supportive care screening, early integration of supportive care into routine cancer care, early implementation of outpatient-based advance care planning, and utilization of electronic patient-reported outcomes for improved symptom management and quality of life. The most common symptoms experienced are nausea, constipation, weight loss, diarrhea, anorexia, and abdominal and back pain. This review article includes current supportive management strategies for these and others. Common disease-related complications include biliary and duodenal obstruction requiring endoscopic procedures and venous thromboembolic events. Patients with PDAC continue to have a poor prognosis. Systemic therapy options are able to palliate the high symptom burden but have a modest impact on overall survival. Early integration of supportive care can lead to improved outcomes.

Phase II study of trastuzumab with modified docetaxel, cisplatin, and 5 fluorouracil in metastatic HER2-positive gastric cancer.

BACKGROUND: Trastuzumab with cisplatin and fluoropyrimidine is the standard treatment in metastatic HER2-positive gastric or gastroesophageal (GE) junction adenocarcinoma; however, there is limited data on the efficacy of trastuzumab in combination with a three-drug regimen in this setting. We examined the efficacy and safety of modified docetaxel, cisplatin and 5 fluorouracil (mDCF) plus trastuzumab in a single-arm multicenter phase II trial. METHODS: Previously untreated patients with HER2-positive metastatic gastric or GE junction adenocarcinoma were treated with mDCF and trastuzumab every 2 weeks. The primary endpoint was 6-month progression-free survival (PFS); secondary endpoints included objective response rate, overall survival (OS), and toxicity. RESULTS: We enrolled 26 patients with metastatic HER2-positive gastric or GE junction adenocarcinoma between February 2011 and June 2015. The median age of patients was 62 years; 96% had a Karnofsky performance status equal to or greater than 80%. With a median follow-up of 25.4 months, the 6-month PFS was 73% (95% CI 51-86%). The objective response rate was 65%, the median PFS was 13 months (95% CI 6.4-20.7) and the median OS was 24.9 months (95% CI 14.4-42.5). Grade 3/4 toxicities included neutropenia (42%), fatigue (23%), and hypophosphatemia (15%). There were no episodes of febrile neutropenia. CONCLUSION: The combination of mDCF and trastuzumab is effective and safe in patients with metastatic HER2-positive gastric or GE junction adenocarcinoma and can be considered as an option for selected patients. This trial is registered at ClinicalTrials.gov, number NCT00515411.

What if Acupuncture Were Covered by Insurance for Pain Management? A Cross-Sectional Study of Cancer Patients at One Academic Center and 11 Community Hospitals.

OBJECTIVE: In response to the national opioid crisis, governmental and medical organizations have called for broader insurance coverage of acupuncture to improve access to nonpharmacologic pain therapies, especially in cancer populations, where undertreatment of pain is prevalent. We evaluated whether cancer patients would be willing to use insurance-covered acupuncture for pain. DESIGN AND SETTING: We conducted a cross-sectional survey of cancer patients with pain at one academic center and 11 community hospitals. METHODS: We used logistic regression models to examine factors associated with willingness to use insurance-covered acupuncture for pain. RESULTS: Among 634 cancer patients, 304 (47.9%) reported willingness to use insurance-covered acupuncture for pain. In univariate analyses, patients were more likely to report willingness if they had severe pain (odds ratio [OR] = 1.59, 95% confidence interval [CI] = 1.03-2.45) but were less likely if they were nonwhite (OR = 0.59, 95% CI = 0.39-0.90) or had only received high school education or less (OR = 0.46, 95% CI = 0.32-0.65). After adjusting for attitudes and beliefs in multivariable analyses, willingness was no longer significantly associated with education (adjusted OR [aOR] = 0.78, 95% CI = 0.50-1.21) and was more negatively associated with nonwhite race (aOR = 0.49, 95% CI = 0.29-0.84). CONCLUSIONS: Approximately one in two cancer patients was willing to use insurance-covered acupuncture for pain. Willingness was influenced by patients' attitudes and beliefs, which are potentially modifiable through counseling and education. Further research on racial disparities is needed to close the gap in utilization as acupuncture is integrated into insurance plans in response to the opioid crisis.

Phase 1 trial evaluating cisplatin, gemcitabine, and veliparib in 2 patient cohorts: Germline BRCA mutation carriers and wild-type BRCA pancreatic ductal adenocarcinoma.

BACKGROUND: A phase 1 trial was used to evaluate a combination of cisplatin, gemcitabine, and escalating doses of veliparib in patients with untreated advanced pancreatic ductal adenocarcinoma (PDAC) in 2 cohorts: a germline BRCA1/2-mutated (BRCA+) cohort and a wild-type BRCA (BRCA-) cohort. The aims were to determine the safety, dose-limiting toxicities (DLTs), maximum tolerated dose, and recommended phase 2 dose (RP2D) of veliparib combined with cisplatin and gemcitabine and to assess the antitumor efficacy (Response Evaluation Criteria in Solid Tumors, version 1.1) and overall survival. METHODS: Gemcitabine and cisplatin were dosed at 600 and 25 mg/m2 , respectively, over 30 minutes on days 3 and 10 of a 21-day cycle. Four dose levels of veliparib were evaluated: 20 (dose level 0), 40 (dose level 1), and 80 mg (dose level 2) given orally twice daily on days 1 to 12 and 80 mg given twice daily on days 1 to 21 (dose level 2A [DL2A]). RESULTS: Seventeen patients were enrolled: 9 BRCA+ patients, 7 BRCA- patients, and 1 patient with an unknown status. DLTs were reached at DL2A (80 mg twice daily on days 1 to 21). Two of the 5 patients in this cohort (40%) experienced grade 4 neutropenia and thrombocytopenia. Two grade 5 events occurred on protocol. The objective response rate in the BRCA+ cohort was 7 of 9 (77.8%). The median overall survival for BRCA+ patients was 23.3 months (95% confidence interval [CI], 3.8-30.2 months). The median overall survival for BRCA- patients was 11 months (95% CI, 1.5-12.1 months). CONCLUSIONS: The RP2D of veliparib was 80 mg by mouth twice daily on days 1 to 12 in combination with cisplatin and gemcitabine; the DLT was myelosuppression. Substantial antitumor activity was seen in BRCA+ PDAC. A randomized phase 2 trial is currently evaluating cisplatin and gemcitabine with and without veliparib for BRCA+ PDAC (NCT01585805). Cancer 2018;124:1374-82. © 2018 American Cancer Society.