Survivorship Care for People Affected by Advanced or Metastatic Cancer: MASCC-ASCO Standards and Practice Recommendations.

PURPOSE: People with advanced or metastatic cancer and their caregivers may have different care goals and face unique challenges compared with those with early-stage disease or those nearing the end of life. These Multinational Association for Supportive Care in Cancer (MASCC)-ASCO standards and practice recommendations seek to establish consistent provision of quality survivorship care for people affected by advanced or metastatic cancer. METHODS: A MASCC-ASCO expert panel was formed. Standards and recommendations relevant to the provision of quality survivorship care for people affected by advanced or metastatic cancer were developed through conducting (1) a systematic review of unmet supportive care needs; (2) a scoping review of cancer survivorship, supportive care, and palliative care frameworks and guidelines; and (3) an international modified Delphi consensus process. RESULTS: A systematic review involving 81 studies and a scoping review of 17 guidelines and frameworks informed the initial standards and recommendations. Subsequently, 77 experts (including eight people with lived experience) across 33 countries (33% were low- to middle-resource countries) participated in the Delphi study and achieved ≥94.8% agreement for seven standards, (1) Person-Centered Care; (2) Coordinated and Integrated Care; (3) Evidence-Based and Comprehensive Care; (4) Evaluated and Communicated Care; (5) Accessible and Equitable Care; (6) Sustainable and Resourced Care; and (7) Research and Data-Driven Care, and ≥84.2% agreement across 45 practice recommendations. CONCLUSION: Standards of survivorship care for people affected by advanced or metastatic cancer are provided. These MASCC-ASCO standards support optimization of health outcomes and care experiences by providing guidance to stakeholders (health care professionals, leaders, and administrators; governments and health ministries; policymakers; advocacy agencies; cancer survivors and caregivers). Practice recommendations may be used to facilitate future research, practice, policy, and advocacy efforts.Additional information is available at www.mascc.org, www.asco.org/standards and www.asco.org/survivorship-guidelines.

Survivorship care for people affected by advanced or metastatic cancer: MASCC-ASCO standards and practice recommendations.

PURPOSE: People with advanced or metastatic cancer and their caregivers may have different care goals and face unique challenges compared to those with early-stage disease or those nearing the end-of-life. These MASCC-ASCO standards and practice recommendations seek to establish consistent provision of quality survivorship care for people affected by advanced or metastatic cancer. METHODS: An expert panel comprising MASCC and ASCO members was formed. Standards and recommendations relevant to the provision of quality survivorship care for people affected by advanced or metastatic cancer were developed through conducting: (1) a systematic review of unmet supportive care needs; (2) a scoping review of cancer survivorship, supportive care, and palliative care frameworks and guidelines; and (3) an international modified Delphi consensus process. RESULTS: A systematic review involving 81 studies and a scoping review of 17 guidelines and frameworks informed the initial standards and recommendations. Subsequently, 77 experts (including 8 people with lived experience) across 33 countries (33% were low-to-middle resource countries) participated in the Delphi study and achieved ≥ 94.8% agreement for seven standards (1. Person-Centred Care; 2. Coordinated and Integrated Care; 3. Evidence-Based and Comprehensive Care; 4. Evaluated and Communicated Care; 5. Accessible and Equitable Care; 6. Sustainable and Resourced Care; 7. Research and Data-Driven Care) and ≥ 84.2% agreement across 45 practice recommendations. CONCLUSION: Standards of survivorship care for people affected by advanced or metastatic cancer are provided. These MASCC-ASCO standards will support optimization of health outcomes and care experiences by providing guidance to stakeholders in cancer care (healthcare professionals, leaders, and administrators; governments and health ministries; policymakers; advocacy agencies; cancer survivors and caregivers. Practice recommendations may be used to facilitate future research, practice, policy, and advocacy efforts.

Views of admitted palliative care patients and their clinicians on corneal donation discussions: a qualitative content analysis of semi-structured interviews.

BACKGROUND: There is a severe shortage of corneas for donation, globally, for transplantation and research purposes. One group of individuals who could potentially be donors are those who die within the inpatient palliative care unit. The aim of the study was to understand clinician and patient perceptions of corneal donations and discussion of donation in palliative care units. METHODS: A qualitative design was utilised with data collected through semi-structured interviews and analysed using qualitative content analysis. A total of 46 interviews were undertaken involving inpatient palliative care unit patients (19) and clinicians (27) in three major inpatient palliative care units in South Australia. RESULTS: Very few patient participants reported being asked about corneal donations during their time in palliative care. Most inpatient palliative care unit clinicians did not raise the topic as they felt other areas of care took precedence. Inpatient palliative care unit patients thought if inpatient palliative care unit clinicians did not raise the topic, then it was not important. There were some differences between patient and clinician views, such as preference about who raises the possibility of donation and when the discussion might occur. CONCLUSIONS: Findings suggest that patients are receptive to discussing corneal donations, but clinicians are not initiating these. This is a missed opportunity for donors and potential recipients. We recommend that clinicians routinely discuss eye donation as part of palliative care.

Subcutaneous sodium valproate in palliative care: A systematic review.

BACKGROUND: Seizures are an important palliative symptom, the management of which can be complicated by patients' capacity to swallow oral medications. In this setting, and the wish to avoid intravenous access, subcutaneous infusions may be employed. Options for antiseizure medications that can be provided subcutaneously may be limited. Subcutaneous sodium valproate may be an additional management strategy. AIM: To evaluate the published experience of subcutaneous valproate use in palliative care, namely with respect to effectiveness and tolerability. DESIGN: A systematic review was registered (PROSPERO CRD42023453427), conducted and reported according to PRISMA reporting guidelines. DATA SOURCES: The databases PubMed, EMBASE and Scopus were searched for publications until August 11, 2023. RESULTS: The searches returned 429 results, of which six fulfilled inclusion criteria. Case series were the most common study design, and most studies included <10 individuals who received subcutaneous sodium valproate. There were three studies that presented results on the utility of subcutaneous sodium valproate for seizure control, which described it to be an effective strategy. One study also described it as an effective treatment for neuropathic pain. The doses were often based on presumed 1:1 oral to subcutaneous conversion ratios. Only one study described a local site adverse reaction, which resolved with a change of administration site. CONCLUSIONS: There are limited data on the use of subcutaneous sodium valproate in palliative care. However, palliative symptoms for which subcutaneous sodium valproate have been used successfully are seizures and neuropathic pain. The available data have described few adverse effects, supporting its use with an appropriate degree of caution.

Multinational Association of Supportive Care in Cancer (MASCC) expert opinion/guidance on the use of clinically assisted hydration in patients with advanced cancer.

PURPOSE: The provision of clinically assisted hydration (CAH) in patients with advanced cancer is controversial, and there is a paucity of specific guidance and so a diversity in clinical practice. Consequently, the Palliative Care Study Group of the Multinational Association of Supportive Care in Cancer (MASCC) formed a sub-group to develop evidence-based guidance on the use of CAH in patients with advanced cancer. METHODS: This guidance was developed in accordance with the MASCC Guidelines Policy. A search strategy for Medline was developed, and the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials were explored for relevant reviews/trials, respectively. RESULTS: Due to the paucity of evidence, the sub-group was not able to develop a prescribed guideline, but was able to generate a number of "expert opinion statements": these statements relate to assessment of patients, indications for CAH, contraindications for CAH, procedures for initiating CAH, and reassessment of patients. CONCLUSIONS: This guidance provides a framework for the use of CAH in advanced cancer, although every patient requires individualised management.

Chromatin Remodeling in Patient-Derived Colorectal Cancer Models.

Patient-Derived Organoids (PDO) and Xenografts (PDX) are the current gold standards for patient-derived models of cancer (PDMC). Nevertheless, how patient tumor cells evolve in these models and the impact on drug response remains unclear. Herein, the transcriptomic and chromatin accessibility landscapes of matched colorectal cancer (CRC) PDO, PDX, PDO-derived PDX (PDOX), and original patient tumors (PT) are compared. Two major remodeling axes are discovered. The first axis delineates PDMC from PT, and the second axis distinguishes PDX and PDO. PDOX are more similar to PDX than PDO, indicating the growth environment is a driving force for chromatin adaptation. Transcription factors (TF) that differentially bind to open chromatins between matched PDO and PDOX are identified. Among them, KLF14 and EGR2 footprints are enriched in PDOX relative to matched PDO, and silencing of KLF14 or EGR2 promoted tumor growth. Furthermore, EPHA4, a shared downstream target gene of KLF14 and EGR2, altered tumor sensitivity to MEK inhibitor treatment. Altogether, patient-derived CRC cells undergo both common and distinct chromatin remodeling in PDO and PDX/PDOX, driven largely by their respective microenvironments, which results in differences in growth and drug sensitivity and needs to be taken into consideration when interpreting their ability to predict clinical outcome.

Should Cannabis be Used for Anorexia in Patients With Cancer?

Healthcare professionals are frequently asked about the benefits of cannabis for appetite or anorexia-cachexia syndrome. In popular culture, cannabis has a reputation of causing an increased hunger, slang termed "the munchies," so many patients consume this with the hope that it may improve the loss of appetite associated with serious illness such as cancer. There have only been a few randomized, controlled trials studying the controversial question as to if cannabis improves appetite. These studies are small and show no statistically significant benefit for appetite and one small study showed improvement of taste for foods. Due to regulation barriers, the studies have use synthetic products, not the products that represent what is more commonly used in the population, often whole flower smoked, vaporized or oral products. Despite the popularity of cannabis in culture, often touted as a panacea for all maladies, the evidence and education for several adverse effects and potential drug interactions have has yet to catch up with the cultural craze. International cannabis experts in the United States and Australia do not routinely certify patients for medical cannabis off trial for anorexia-cachexia, but one expert in Canada would consider use in selected cancer patients.

Epstein-Barr virus induces germinal center light zone chromatin architecture and promotes survival through enhancer looping at the BCL2A1 locus.

IMPORTANCE: Epstein-Barr virus has evolved with its human host leading to an intimate relationship where infection of antibody-producing B cells mimics the process by which these cells normally recognize foreign antigens and become activated. Virtually everyone in the world is infected by adulthood and controls this virus pushing it into life-long latency. However, immune-suppressed individuals are at high risk for EBV+ cancers. Here, we isolated B cells from tonsils and compare the underlying molecular genetic differences between these cells and those infected with EBV. We find similar regulatory mechanism for expression of an important cellular protein that enables B cells to survive in lymphoid tissue. These findings link an underlying relationship at the molecular level between EBV-infected B cells in vitro with normally activated B cells in vivo. Our studies also characterize the role of a key viral control mechanism for B cell survival involved in long-term infection.

Supporting gut health with medicinal cannabis in people with advanced cancer: potential benefits and challenges.

The side effects of cancer therapy continue to cause significant health and cost burden to the patient, their friends and family, and governments. A major barrier in the way in which these side effects are managed is the highly siloed mentality that results in a fragmented approach to symptom control. Increasingly, it is appreciated that many symptoms are manifestations of common underlying pathobiology, with changes in the gastrointestinal environment a key driver for many symptom sequelae. Breakdown of the mucosal barrier (mucositis) is a common and early side effect of many anti-cancer agents, known to contribute (in part) to a range of highly burdensome symptoms such as diarrhoea, nausea, vomiting, infection, malnutrition, fatigue, depression, and insomnia. Here, we outline a rationale for how, based on its already documented effects on the gastrointestinal microenvironment, medicinal cannabis could be used to control mucositis and prevent the constellation of symptoms with which it is associated. We will provide a brief update on the current state of evidence on medicinal cannabis in cancer care and outline the potential benefits (and challenges) of using medicinal cannabis during active cancer therapy.

An evidence-base for the implementation of hospital-based palliative care programs in routine cancer practice: A systematic review.

BACKGROUND: Despite global support, there remain gaps in the integration of early palliative care into cancer care. The methods of implementation whereby evidence of benefits of palliative care is translated into practice deserve attention. AIM: To identify implementation frameworks utilised in integrated palliative care in hospital-based oncology services and to describe the associated enablers and barriers to service integration. DESIGN: Systematic review with a narrative synthesis including qualitative, mixed methods, pre-post and quasi experimental designs following the guidance by the Centre for Reviews and Dissemination (PROSPERO registration CRD42021252092). DATA SOURCES: Six databases searched in 2021: EMBASE, EMCARE, APA PsycINFO, CINAHL, Cochrane Library and Ovid MEDLINE searched in 2023. Included were qualitative or quantitative studies, in English language, involving adults >18 years, and implementing hospital-based palliative care into cancer care. Critical appraisal tools were used to assess the quality and rigour. RESULTS: Seven of the 16 studies explicitly cited the use of frameworks including those based on RE-AIM, Medical Research Council evaluation of complex interventions and WHO constructs of health service evaluation. Enablers included an existing supportive culture, clear introduction to the programme across services, adequate funding, human resources and identification of advocates. Barriers included a lack of communication with the patients, caregivers, physicians and palliative care team about programme goals, stigma around the term 'palliative', a lack of robust training, or awareness of guidelines and undefined staff roles. CONCLUSIONS: Implementation science frameworks provide a method to underpin programme development and evaluation as palliative care is integrated within the oncology setting.

'The palliative care ambulance': A qualitative study of patient and caregiver perspectives of an ambulance service.

BACKGROUND: The need for home-based palliative care is accelerating internationally. At the same time, health systems face increased complexity, funding constraints and global shortages in the healthcare workforce. As such, ambulance services are increasingly tasked with providing palliative care. Where paramedics with additional training in palliative care have been integrated into models of care, evaluations have been largely positive. Studies of patient and family carer experiences of paramedic involvement, however, are limited. AIM: To explore patient and family caregiver experiences of paramedics' contribution to palliative care at home. DESIGN: Qualitative interview study. We analysed data within a social constructionist epistemology using reflexive thematic analysis. SETTING/PARTICIPANTS: Participants receiving specialist palliative care in the community of a metropolitan city of Australia who requested an ambulance between January and August 2018, inclusive. RESULTS: Participants considered paramedics with expertise and experience in palliative care as an extension of the specialist community palliative care team and held them in high regard. Participants highlighted the importance of: critical palliative care at home and a timely, responsive approach; person-centred paramedics; as well as safety and security. CONCLUSION: Patients and carers feel safe and secure when they know that highly responsive skilled professional support is available when an unexpected problem or sudden change arises, especially out-of-hours, and that support is delivered in an empathic and person-centred manner.

MASCC guideline: cannabis for cancer-related pain and risk of harms and adverse events.

BACKGROUND: Approximately 18% of patients with cancer use cannabis at one time as palliation or treatment for their cancer. We performed a systematic review of randomized cannabis cancer trials to establish a guideline for its use in pain and to summarize the risk of harm and adverse events when used for any indication in cancer patients. METHODS: A systematic review of randomized trials with or without meta-analysis was carried out from MEDLINE, CCTR, Embase, and PsychINFO. The search involved randomized trials of cannabis in cancer patients. The search ended on November 12, 2021. The Jadad grading system was used for grading quality. Inclusion criteria for articles were randomized trials or systematic reviews of randomized trials of cannabinoids versus either placebo or active comparator explicitly in adult patients with cancer. RESULTS: Thirty-four systematic reviews and randomized trials met the eligibility criteria for cancer pain. Seven were randomized trials involving patients with cancer pain. Two trials had positive primary endpoints, which could not be reproduced in similarly designed trials. High-quality systematic reviews with meta-analyses found little evidence that cannabinoids are an effective adjuvant or analgesic to cancer pain. Seven systematic reviews and randomized trials related to harms and adverse events were included. There was inconsistent evidence about the types and levels of harm patients may experience when using cannabinoids. CONCLUSION: The MASCC panel recommends against the use of cannabinoids as an adjuvant analgesic for cancer pain and suggests that the potential risk of harm and adverse events be carefully considered for all cancer patients, particularly with treatment with a checkpoint inhibitor.

Multinational Association of Supportive Care in Cancer (MASCC) guidelines: cannabis for psychological symptoms including insomnia, anxiety, and depression.

PURPOSE: During the treatment of cancer, 18% of patients use cannabis for symptom management. Anxiety, depression, and sleep disturbances are common symptoms in cancer. A systematic review of the evidence for cannabis use for psychological symptoms in cancer patients was undertaken to develop a guideline. METHODS: A literature search of randomized trials and systematic reviews was undertaken up to November 12, 2021. Studies were independently assessed for evidence by two authors and then evaluated by all authors for approval. The literature search involved MEDLINE, CCTR, EMBASE, and PsychINFO databases. Inclusion criteria included randomized control trials and systematic reviews on cannabis versus placebo or active comparator in patients with cancer and psychological symptom management (anxiety, depression, and insomnia). RESULTS: The search yielded 829 articles; 145 from Medline, 419 from Embase, 62 from PsychINFO, and 203 from CCTR. Two systematic reviews and 15 randomized trials (4 on sleep, 5 on mood, 6 on both) met eligibility criteria. However, no studies specifically assessed the efficacy of cannabis on psychological symptoms as primary outcomes in cancer patients. The studies varied widely in terms of interventions, control, duration, and outcome measures. Six of 15 RCTs suggested benefits (five for sleep, one for mood). CONCLUSION: There is no high-quality evidence to recommend the use of cannabis as an intervention for psychological symptoms in patients with cancer until more high-quality research demonstrates benefit.

Effects of a prescribed, supervised exercise programme on tumour disease progression in oncology patients undergoing anti-cancer therapy: a retrospective observational cohort study.

BACKGROUND: Exercise promotes numerous advantages in both health and disease, and is increasingly being acknowledged to improve overall survival in cancer patients. Preclinical studies indicate a direct effect on tumour behaviour, but human data on the effect of exercise on tumour progression are lacking. AIMS: To capture preliminary clinical data regarding the impact of a prescribed, supervised exercise programme on cancer disease progression. METHODS: Retrospective cohort study of 137 matched pairs of patients. All patients referred to LIFT Cancer Care Services (LIFT) supervised exercise programme between 2018 and 2019 were matched with non-LIFT patients from the oncology practice database. Disease progression via staging computed tomography scans ± tumour markers was compared for each match. Secondary outcomes were changes in neutrophil-to-lymphocyte ratio (NLR) and death. Results were analysed by logistical regression and adjusted for potential confounders. RESULTS: Patients from the LIFT group had a 66% (OR = 0.34, 95% CI 0.19 to 0.61) decreased odds of disease progression and 76% (OR = 0.24, 95% CI 0.12-0.47) decreased odds of death compared with the non-LIFT group. No effect on the number of LIFT sessions on disease progression was demonstrated. The LIFT group had a mean final NLR reading 3.48 (-5.89 to -1.09) lower than the non-LIFT group. CONCLUSION: Supervised exercise programmes have the potential to significantly improve outcomes in cancer patients due to an effect on tumour progression.

Multinational Association of Supportive Care in Cancer (MASCC) expert opinion/consensus guidance on the use of cannabinoids for gastrointestinal symptoms in patients with cancer.

BACKGROUND: Gastrointestinal symptoms are common in patients with cancer, whether related to treatment or a direct effect of the disease itself. Patients may choose to access cannabinoids outside of their formal medical prescriptions to palliate such symptoms. However, clinical guidelines are lacking in relation to the use of such medicines for gastrointestinal symptoms in patients with cancer. METHODS: A systematic review of the evidence for the use of cannabinoids for symptom control in patients with cancer was undertaken. Search strategies were developed for Medline, Embase, PsychINFO, and the Cochrane Central Register of Controlled Trials, including all publications from 1975 up to 12 November 2021. Studies were included if they were randomized controlled trials of cannabinoids compared with placebo or active comparator in adult patients with cancer, regardless of type, stage, or treatment status. Articles for inclusion were agreed by all authors, and data extracted and summarized by two authors. Each study was scored according to the Jadad scale. This review was specifically for the purpose of developing guidelines for the use of cannabis for gastrointestinal symptoms, including chemotherapy-induced nausea and vomiting (CINV), chronic nausea, anorexia-cachexia syndrome, and taste disturbance. RESULTS: Thirty-six randomized controlled trials were identified that met the inclusion criteria for this review of gastrointestinal symptoms: 31 relating to CINV, one to radiotherapy-induced nausea and vomiting, and the remaining four to anorexia-cachexia and altered chemosensory disturbance. The populations for the randomized controlled trials were heterogeneous, and many studies were of poor quality, lacking clarity regarding method of randomization, blinding, and allocation concealment. For CINV, eleven RCTs showed improvement with cannabis compared to placebo, but out of 21 trials where cannabis was compared to other antiemetics for CINV, only 11 favoured cannabis. CONCLUSION: Tetrahydrocannabinol (THC) and nabilone were more effective in preventing CINV when compared to placebo but are not more effective than other antiemetics. For refractory CINV, one study of THC:CBD demonstrated reduced nausea as an add-on treatment to guideline-consistent antiemetic therapy without olanzapine. The MASCC Guideline Committee found insufficient evidence to recommend cannabinoids for the management of CINV, nausea from advanced cancer, cancer-associated anorexia-cachexia, and taste disturbance. High-quality studies are needed to inform practice.

Opioid Rotation and Conversion Ratios Used by Palliative Care Professionals: An International Survey.

Background: The opioid rotation ratios (ORRs) and conversion ratios (CRs) used worldwide among palliative care (PC) professionals to perform opioid rotations (ORs) and route conversions may have a wide variation. Methods: We surveyed PC professionals on opioid ratios used through email to the Multinational Association of Supportive Care in Cancer's PC study group and Twitter and Facebook posts between September and November 2020. Results: We received 370 responses from respondents from 53 countries: 276 (76%) were physicians, 46 (13%) advanced practice providers, 39 (11%) pharmacists, and 9 respondents did not report their profession. There were statistically significant variations in median CR from intravenous (IV) to oral morphine (2-3), IV to oral hydromorphone (2-4.5), ORR from IV hydromorphone to oral morphine (10-20), and ORR from transdermal fentanyl mcg/hour to oral morphine (2-3.5) across various groups. Conclusion: This survey highlights the wide variation in ORRs and CRs among PC clinicians worldwide and the need for further research to standardize practice.