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.

TEMPORARY REMOVAL: Opportunities to Improve End-of-Life Care Quality among Patients with Short Terminal Admissions.

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Creating a Palliative Care Clinic for Patients with Cancer Pain and Substance Use Disorder.

BACKGROUND: Opioids are a first-line treatment for severe cancer pain. However, clinicians may be reluctant to prescribe opioids for patients with concurrent substance use disorders (SUD) or clinical concerns about non-prescribed substance use. MEASURES: Patient volume, 60-day retention rate, and use of sublingual buprenorphine to treat opioid use disorder. INTERVENTION: We created the Palliative Harm Reduction and Resiliency Clinic, a palliative care clinic founded on harm reduction principles and including formal collaboration with addiction psychiatry. OUTCOMES: During the first 18 months, patient volume increased steadily; 70% of patients had at least one subsequent visit within 60 days of the initial appointment; and buprenorphine was prescribed for 55% of patients with opioid use disorder. CONCLUSIONS/LESSONS LEARNED: The formal collaboration with addiction psychiatry and the integration of harm reduction principles and practices into ambulatory palliative care improved our ability to provide treatment to a previously underserved patient population with high symptom burden.

Benefits, Harms, and Stakeholder Perspectives Regarding Opioid Therapy for Pain in Individuals With Metastatic Cancer: Protocol for a Descriptive Cohort Study.

BACKGROUND: Opioids are a key component of pain management among patients with metastatic cancer pain. However, the evidence base available to guide opioid-related decision-making in individuals with advanced cancer is limited. Patients with advanced cancer or cancer that is unlikely to be cured frequently experience pain. Opioids are a key component of pain management among patients with metastatic cancer pain. Many individuals with advanced cancer are now living long enough to experience opioid-related harm. Emerging evidence from chronic noncancer pain literature suggests that longer-term opioid therapy may have limited benefits for pain and function, and opioid-related harms are also a major concern. However, whether these benefits and harms of opioids apply to patients with cancer-related pain is unknown. OBJECTIVE: This manuscript outlines the protocol for the "Opioid Therapy for Pain in Individuals With Metastatic Cancer: The Benefits, Harms, and Stakeholder Perspectives (BEST) Study." The study aims to better understand opioid decision-making in patients with advanced cancer, along with opioid benefits and harms, through prospective examination of patients' pain experiences and opioid side effects and understanding the decision-making by patients, care partners, and clinicians. METHODS: This is a multicenter, prospective cohort study that aims to enroll 630 patients with advanced cancer, 20 care partners, and 20 clinicians (670 total participants). Patient participants must have an advanced solid cancer diagnosis, defined by the American Cancer Society as cancer that is unlikely to be cured. We will recruit patient participants within 12 weeks after diagnosis so that we can understand opioid benefits, harms, and perspectives on opioid decision-making throughout the course of their advanced cancer (up to 2 years). We will also specifically elicit information regarding long-term opioid use (ie, opioids for ≥90 consecutive days) and exclude patients on long-term opioid therapy before an advanced cancer diagnosis. Lived-experience perspectives related to opioid use in those with advanced cancer will be captured by qualitative interviews with a subset of patients, clinicians, and care partners. Our data collection will be grounded in a behavioral decision research approach that will allow us to develop future interventions to inform opioid-related decision-making for patients with metastatic cancer. RESULTS: Data collection began in October 2022 and is anticipated to end by November 2024. CONCLUSIONS: Upon successful execution of our study protocol, we anticipate the development of a comprehensive evidence base on opioid therapy in individuals with advanced cancer guided by the behavioral decision research framework. The information gained from this study will be used to guide interventions to facilitate opioid decisions among patients, clinicians, and care partners. Given the limited evidence base about opioid therapy in people with cancer, we envision this study will have significant real-world implications for cancer-related pain management and opioid-related clinical decision-making. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54953.

Experiences of Aging with Opioid Use Disorder and Comorbidity in Opioid Treatment Programs: A Qualitative Analysis.

BACKGROUND: The number of older adults entering opioid treatment programs (OTPs) to treat opioid use disorder (OUD) is increasing. However, the lived experiences of aging in OTPs have not been examined. OBJECTIVE: To explore the aging experience with OUD and barriers to medical care for older adults who receive care in OTPs. DESIGN: From November 2021 to July 2022, we conducted 1-to-1, semi-structured qualitative interviews in English and Spanish, audio-recorded, transcribed, systematically coded, and analyzed to identify key themes regarding the challenges of aging with OUD and managing chronic diseases. PARTICIPANTS: Thirty-six adults aged ≥ 55 enrolled in OTPs in San Diego, California. APPROACH: A descriptive qualitative approach was used. Major themes and subthemes were identified through thematic analysis until thematic saturation was reached. KEY RESULTS: All participants were on methadone and had a mean age of 63.4 (SD 5.1) years; 11 (30.6%) identified as female, 14 (39%) as Hispanic/Latino, and 11 (36%) as Black, with a mean duration of methadone treatment of 5.6 years. Chronic diseases were common, with 21 (58.3%) reporting hypertension, 9 (25%) reporting untreated hepatitis C, and 32 (88.9%) having ≥ 2 chronic diseases. Three major themes emerged: (1) avoidance of medical care due to multiple intersectional stigmas, including those related to drug use, substance use disorder (SUD) treatment, ageism, and housing insecurity; (2) increasing isolation with aging and loss of family and peer groups; (3) the urgent need for integrating medical and aging-focused care with OUD treatment in the setting of increasing health and functional challenges. CONCLUSIONS: Older adults with OUD reported increasing social isolation and declining health while experiencing multilevel stigma and discrimination. The US healthcare system must transform to deliver age-friendly care that integrates evidence-based geriatric models of care incorporated with substance use disorder treatment and addresses the intersectional stigma this population has experienced in healthcare settings.

Substance Use Disorders Among US Adult Cancer Survivors.

Importance: Some individuals are predisposed to cancer based on their substance use history, and others may use substances to manage cancer-related symptoms. Yet the intersection of substance use disorder (SUD) and cancer is understudied. Because SUD may affect and be affected by cancer care, it is important to identify cancer populations with a high prevalence of SUD, with the goal of guiding attention and resources toward groups and settings where interventions may be needed. Objective: To describe the cancer type-specific prevalence of SUD among adult cancer survivors. Design, Setting, and Participants: This cross-sectional study used data from the annually administered National Survey on Drug Use and Health (NSDUH) for 2015 through 2020 to identify adults with a history of solid tumor cancer. Substance use disorder was defined as meeting at least 1 of 4 Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria for abuse or at least 3 of 6 criteria for dependence. Main Outcomes and Measures: Per NSDUH guidelines, we made adjustments to analysis weights by dividing weights provided in the pooled NSDUH data sets by the number of years of combined data (eg, 6 for 2015-2020). The weighted prevalence and corresponding SEs (both expressed as percentages) of active SUD (ie, within the past 12 months) were calculated for respondents with any lifetime history of cancer and, in secondary analyses, respondents diagnosed with cancer within 12 months prior to taking the survey. Data were analyzed from July 2022 to June 2023. Results: This study included data from 6101 adult cancer survivors (56.91% were aged 65 years or older and 61.63% were female). Among lifetime cancer survivors, the prevalence of active SUD was 3.83% (SE, 0.32%). Substance use disorder was most prevalent in survivors of head and neck cancer (including mouth, tongue, lip, throat, and pharyngeal cancers; 9.36% [SE, 2.47%]), esophageal and gastric cancer (9.42% [SE, 5.51%]), cervical cancer (6.24% [SE, 1.41%]), and melanoma (6.20% [SE, 1.34%]). Alcohol use disorder was the most common SUD (2.78% [SE, 0.26%]) overall and in survivors of head and neck cancer, cervical cancer, and melanoma. In survivors of esophageal and gastric cancers, cannabis use disorder was the most prevalent SUD (9.42% [SE, 5.51%]). Among respondents diagnosed with cancer in the past 12 months, the overall prevalence of active SUD was similar to that in the lifetime cancer survivor cohort (3.81% [SE, 0.74%]). However, active SUD prevalence was higher in head and neck (18.73% [SE, 10.56%]) and cervical cancer survivors (15.70% [SE, 5.35%]). The distribution of specific SUDs was different compared with that in the lifetime cancer survivor cohort. For example, in recently diagnosed head and neck cancer survivors, sedative use disorder was the most common SUD (9.81% [SE, 9.17%]). Conclusions and Relevance: Findings of this study suggest that SUD prevalence is higher among survivors of certain types of cancer; this information could be used to identify cancer survivors who may benefit from integrated cancer and SUD care. Future efforts to understand and address the needs of adult cancer survivors with comorbid SUD should prioritize cancer populations in which SUD prevalence is high.

Toward reducing racialized pain care disparities: Approaching cannabis research and access through the lens of equity and inclusion.

There is growing interest in cannabis use for cancer pain. This commentary aims to discuss the evidence surrounding cannabis use for cancer pain in the context of the long-racialized landscape of cannabis policies and the disparity in pain control among cancer patients holding minoritized racial identities. Much evidence surrounding both the benefits and harms of cannabis use in cancer patients, and all patients in general, is lacking. Although drawing on the research in cancer that is available, it is also important to illustrate the broader context about how cannabis' deep roots in medical, political, and social history impact patient use and health care policies. There are lessons we can learn from the racialized disparities in opioid risk mitigation strategies, so they are not replicated in the settings of cannabis for cancer symptom management. Additionally, the authors intentionally use the term "cannabis" here rather than "marijuana.: In the early 1900s, the lay press and government popularized the use of the word "marijuana" instead of the more common "cannabis" to tie the drug to anti-Mexican prejudice.

Managing Chronic Pain in Cancer Survivorship: Communication Challenges and Opportunities as Described by Cancer Survivors.

OBJECTIVES: Many cancer survivors experience chronic pain after completing curative-intent treatment. Based on available data, chronic pain may be undertreated in this context; however, little is known about cancer survivors' experiences with clinical management of chronic pain. The purpose of this study was to better understand cancer survivors' pain management experiences after curative-intent treatment. METHODS: We conducted 13 semi-structured interviews with a convenience sample of cancer survivors who had completed treatment for stage I-III breast, head/neck, lung or colorectal cancer. We used a thematic approach to qualitative data analysis. RESULTS: Participants described that chronic pain often goes unrecognized by their providers, potentially due to limitations in how pain is assessed clinically and the tendency of both cancer survivors and providers to minimize or invalidate the pain experience. To improve communication, participants suggested that providers ask more open-ended questions about their pain, help them to establish functional goals, and provide patients with options for pain management. SIGNIFICANCE OF RESULTS: This study demonstrates the importance of provider-initiated communication around pain management for cancer survivors to make them feel more supported in their care. Communication and shared decision-making interventions may improve cancer survivor-provider communication around chronic pain management, addressing an important gap in survivorship care.

A 3D adrenocortical carcinoma tumor platform for preclinical modeling of drug response and matrix metalloproteinase activity.

Adrenocortical carcinoma (ACC) has a poor prognosis, and no new drugs have been identified in decades. The absence of drug development can partly be attributed to a lack of preclinical models. Both animal models and 2D cell cultures of ACC fail to accurately mimic the disease, as animal physiology is inherently different than humans, and 2D cultures fail to represent the crucial 3D architecture. Organoids and other small 3D in vitro models of tissues or tumors can model certain complexities of human in vivo biology; however, this technology has largely yet to be applied to ACC. In this study, we describe the generation of 3D tumor constructs from an established ACC cell line, NCI-H295R. NCI-H295R cells were encapsulated to generate 3D ACC constructs. Tumor constructs were assessed for biomarker expression, viability, proliferation, and cortisol production. In addition, matrix metalloproteinase (MMP) functionality was assessed directly using fluorogenic MMP-sensitive biosensors and through infusion of NCI-H295R cells into a metastasis-on-a-chip microfluidic device platform. ACC tumor constructs showed expression of biomarkers associated with ACC, including SF-1, Melan A, and inhibin α. Treatment of ACC tumor constructs with chemotherapeutics demonstrated decreased drug sensitivity compared to 2D cell culture. Since most tumor cells migrate through tissue using MMPs to break down extracellular matrix, we validated the utility of ACC tumor constructs by integrating fluorogenic MMP-sensitive peptide biosensors within the tumor constructs. Lastly, in our metastasis-on-a-chip device, NCI-H295R cells successfully engrafted in a downstream lung cell line-based construct, but invasion distance into the lung construct was decreased by MMP inhibition. These studies, which would not be possible using 2D cell cultures, demonstrated that NCI-H295R cells secreted active MMPs that are used for invasion in 3D. This work represents the first evidence of a 3D tumor constructs platform for ACC that can be deployed for future mechanistic studies as well as development of new targets for intervention and therapies.

Expert consensus-based guidance on approaches to opioid management in individuals with advanced cancer-related pain and nonmedical stimulant use.

BACKGROUND: Clinicians treating cancer-related pain with opioids regularly encounter nonmedical stimulant use (i.e., methamphetamine, cocaine), yet there is little evidence-based management guidance. The aim of the study is to identify expert consensus on opioid management strategies for an individual with advanced cancer and cancer-related pain with nonmedical stimulant use according to prognosis. METHODS: The authors conducted two modified Delphi panels with palliative care and addiction experts. In Panel A, the patient's prognosis was weeks to months and in Panel B the prognosis was months to years. Experts reviewed, rated, and commented on the case using a 9-point Likert scale from 1 (very inappropriate) to 9 (very appropriate) and explained their responses. The authors applied the three-step analytical approach outlined in the RAND/UCLA to determine consensus and level of clinical appropriateness of management strategies. To better conceptualize the quantitative results, they thematically analyzed and coded participant comments. RESULTS: Consensus was achieved for all management strategies. The 120 Experts were mostly women (47 [62%]), White (94 [78%]), and physicians (115 [96%]). For a patient with cancer-related and nonmedical stimulant use, regardless of prognosis, it was deemed appropriate to continue opioids, increase monitoring, and avoid opioid tapering. Buprenorphine/naloxone transition was inappropriate for a patient with a short prognosis and of uncertain appropriateness for a patient with a longer prognosis. CONCLUSION: Study findings provide urgently needed consensus-based guidance for clinicians managing cancer-related pain in the context of stimulant use and highlight a critical need to develop management strategies to address stimulant use disorder in people with cancer. PLAIN LANGUAGE SUMMARY: Among palliative care and addiction experts, regardless of prognosis, it was deemed appropriate to continue opioids, increase monitoring, and avoid opioid tapering in the context of cancer-related pain and nonmedical stimulant use. Buprenorphine/naloxone transition as a harm reduction measure was inappropriate for a patient with a short prognosis and of uncertain appropriateness for a patient with a longer prognosis.

Compassionate Care for People with Cancer and Opioid Use Disorder.

ABSTRACT: Opioid use disorder (OUD) is an important comorbidity to assess and manage in people with cancer. In this article, the authors discuss strategies for safe opioid management in individuals with OUD and cancer-related pain using a composite case example. They highlight core approaches to pain management, including motivational interviewing, harm reduction, and evidence-based treatments, as well as advocacy for person-centered end-of-life care.

The Contribution of Cancer-Specific Psychosocial Factors to the Pain Experience in Cancer Survivors.

Palliative care teams are increasingly called up to manage chronic pain in cancer survivors. Chronic pain is common in cancer survivors and is heavily influenced by biopsychosocial factors. This study aimed to determine the relative contribution of unique cancer-specific psychosocial factors, pain catastrophizing, and multisite pain to the pain experience in 41 cancer survivors who completed curative cancer treatment. To test the research hypotheses, a series of nested linear regression models were used with likelihood ratio testing to test the individual and collective contribution of cancer-specific psychosocial factors (fear of cancer recurrence, cancer distress, cancer-related trauma), pain catastrophizing, and the number of pain sites on the pain experience. The results indicate pain catastrophizing and multisite pain explained a significant degree of variance in pain interference scores ( P < .001) and pain severity ( P = .005). Cancer-specific psychosocial factors did not significantly predict variability in pain interference ( P = .313) or pain severity ( P = .668) over and above pain catastrophizing and the number of sites of pain. In summary, pain catastrophizing and multisite pain contribute to the chronic cancer-related pain experienced by cancer survivors. Palliative care nurses are well positioned to improve chronic pain among cancer survivors by assessing and treating pain catastrophizing and multisite pain.

SIO-ASCO guideline on integrative medicine for cancer pain management: implications for racial and ethnic pain disparities.

Racial and ethnic disparities in pain management pose major challenges to equitable cancer care delivery. These disparities are driven by complex interactions between patient-, provider-, and system-related factors that resist reductionistic solutions and require innovative, holistic approaches. On September 19, 2022, the Society for Integrative Oncology and the American Society of Clinical Oncology published a joint guideline to provide evidence-based recommendations on integrative medicine for cancer pain management. Integrative medicine, which combines conventional treatments with complementary modalities from cultures and traditions around the world, are uniquely equipped to resonate with diverse cancer populations and fill existing gaps in pain management. Although some complementary modalities, such as music therapy and yoga, lack sufficient evidence to make a specific recommendation, other modalities, such as acupuncture, massage, and hypnosis, demonstrated an intermediate level of evidence, resulting in moderate strength recommendations for their use in cancer pain management. However, several factors may hinder real-world implementation of the Society for Integrative Oncology and the American Society of Clinical Oncology guideline and must be addressed to ensure equitable pain management for all communities. These barriers include, but are not limited to, the lack of insurance coverage for many complementary therapies, the limited diversity and availability of complementary therapy providers, the negative social norms surrounding complementary therapies, the underrepresentation of racial and ethnic subgroups in the clinical research of complementary therapies, and the paucity of culturally attuned interventions tailored to diverse individuals. This commentary examines both the challenges and the opportunities for addressing racial and ethnic disparities in cancer pain management through integrative medicine.

A Randomized Control Trial to Test Dissemination of an Online Suicide Prevention Training For Intimate Partner Violence Hotline Workers.

Purpose: Suicide risk is higher among violence-involved individuals. Intimate Partner Violence hotline workers are a critical source of support and can potentially be suicide prevention champions. Our primary goal was to examine the effectiveness of disseminating a free, online IPV-Suicide Prevention curriculum, via a randomized control trial, to hotline workers in ten states with the highest suicide and IPV homicide rates. Method: We divided the country into five regions and, based on criterion, chose two states in each region to randomize into the two arms of the study. We examined training participation and engagement between the two approaches: (1) 'dissemination as usual' (control) using a National Domestic Violence Hotline email and a postcard to state/county IPV directors, versus (2) 'enhanced dissemination' (intervention) using a four-point touch method (postcard, phone call, email, and letter) to 'drive' participation. Results: Participation increased in the intervention arm as approaches became more personal (i.e., email and phone calls vs. letters). Results indicate that traditional dissemination strategies such as email announcements and invitations are not as effective as varied and multiple touchpoints for IPV hotline staff. Conclusion: Successful dissemination strategies to promote digital training should consider the value added by personalized connection. Future research is needed to understand how to offer effective and efficient web-based training to those providing IPV and child abuse services.

Under Pressure: Lamina Cribrosa Pore Path Tortuosity in Response to Acute Pressure Modulation.

Purpose: Lamina cribrosa (LC) deformation is hypothesized to play a major role in glaucoma pathogenesis. The purpose of this study was to determine in vivo how varying intraocular pressure (IOP) under fixed intracranial pressure (ICP), and vice versa, deforms the pore paths throughout the LC volume. Methods: Spectral-domain optical coherence tomography scans of the optic nerve head were acquired from healthy adult rhesus monkeys under different pressures. IOP and ICP were controlled with gravity-based perfusion systems into the anterior chamber and lateral ventricle, respectively. IOP and ICP were modulated from baseline to high (19-30 mmHg) and highest (35-50 mmHg) levels while maintaining a fixed ICP of 8 to 12 mmHg and IOP of 15 mmHg, respectively. After three-dimensional registration and segmentation, the paths of pores visible in all settings were tracked based on their geometric centroids. Pore path tortuosity was defined as the measured distance divided by the minimal distance between the most anterior and posterior centroids. Results: The median pore tortuosity at baseline varied among the eyes (range, 1.16-1.68). For the IOP effect under fixed ICP (six eyes, five animals), two eyes showed statistically significant increased tortuosity and one showed a decrease (P < 0.05, mixed-effects model). No significant change was detected in three eyes. When modulating ICP under fixed IOP (five eyes, four animals), a similar response pattern was detected. Conclusions: Baseline pore tortuosity and the response to acute pressure increase vary substantially across eyes. Translational Relevance: LC pore path tortuosity could be associated with glaucoma susceptibility.

"It Is So Easy For Them to Dismiss": A Phenomenological Study of Cancer Survivors With Chronic Cancer-Related Pain.

Background: For many cancer survivors post-cure, chronic pain is a devastating complication of cancer treatment. The prevalence of chronic pain among cancer survivors is double that of the general population. However, little is known about the pain experience of cancer survivors who may have a different perspective than people with advanced cancer or people with noncancer pain. Objective: To understand the lived experience of chronic cancer-related pain in cancer survivors. Methods: We used a qualitative design with a descriptive phenomenological method to conduct in-depth interviews of 13 cancer survivors residing in the United States who completed curative cancer therapy, were at least three months from treatment, and experienced pain attributable to cancer. Data collection was focused on the lived experience and management of chronic cancer-related pain and a deep understanding of how the experience of chronic cancer-related pain shapes pain management choices. Results: The participants had a variety of primary cancer types and cancer pain syndromes. Three essential themes epitomized the experience of living with chronic cancer-related pain: invisible suffering at the cost of survival, an opioid paradox, and a lack of answers on what to expect and what might help. Conclusion and Implications: The results highlight an opportunity for pain self-management, education, and psychosocial interventions to optimize pain in cancer. Participants' experiences identify several opportunities to improve chronic cancer-related pain. Future efforts should prioritize access to multimodal pain treatments, high-quality communication, and expand clinicians' knowledge and skills to manage chronic pain.

Pharmacologic Pain Management: What Radiation Oncologists Should Know.

Individuals with cancer experience a host of symptoms, especially when the malignancy is advanced. Pain occurs from the cancer itself or related treatments. Undertreated pain contributes to patient suffering and lack of engagement in cancer-directed therapies. Adequate pain management includes thorough assessment; treatment by radiotherapists or anesthesia pain specialists; anti-inflammatory medications, oral or intravenous opioid analgesics, and topical agents; and attention to the emotional and functional effects of pain, which may involve social workers, psychologists, speech therapists, nutritionists, physiatrists and palliative medicine providers. This review discusses typical pain syndromes arising in cancer patients undergoing radiotherapy and provides concrete recommendations for pain assessment and pharmacologic treatment.