Meaningful Patient Engagement in Adolescent and Young Adult (AYA) Cancer Research: A Framework for Qualitative Studies.

Over the last two decades, patient engagement in cancer research has evolved significantly, especially in addressing the unique challenges faced by adolescent and young adult (AYA) cancer populations. This paper introduces a framework for meaningful engagement with AYA cancer patient research partners, drawing insights from the "FUTURE" Study, a qualitative study that utilizes focus groups to explore the impact of cancer diagnosis and treatment on the sexual and reproductive health of AYA cancer patients in Canada. The framework's development integrates insights from prior works and addresses challenges with patient engagement in research specific to AYA cancer populations. The framework is guided by overarching principles (safety, flexibility, and sensitivity) and includes considerations that apply across all phases of a research study (collaboration; iteration; communication; and equity, diversity, and inclusion) and tasks that apply to specific phases of a research study (developing, conducting, and translating the study). The proposed framework seeks to increase patient engagement in AYA cancer research beyond a supplementary aspect to an integral component for conducting research with impact on patients.

Young Women with Breast Cancer: The Current Role of Precision Oncology.

Young adults aged 40 years and younger with breast cancer represent less than 5% of all breast cancer cases, yet it is the leading cause of death among young women with cancer worldwide. Breast cancer that develops at a young age is more aggressive and has biological features that carry an increased risk of relapse and death. Young adults are more likely to have a genetic predisposition and key biomarkers, including endocrine receptors, the HER2 receptor, and proliferation biomarkers, that appear different compared to older adults. Despite being more aggressive, management strategies are largely the same irrespective of age. Given the higher rates of genetic predisposition, fast access to genetic counselling and testing is a necessity. In this review, the biological differences in young adult breast cancer and the current role precision medicine holds in the treatment of young adults with breast cancer are explored. Given the relatively high risk of relapse, developing novel genomic tools to refine the treatment options beyond the current standard is critical. Existing predictive genomic tests require careful interpretation with consideration of the patient's clinical and pathological features in the young patient cohort. Careful evaluation is also required when considering extended endocrine therapy options. Improved characterization of mutations occurring in tumors using next-generation sequencing could identify important driver mutations that arise in young women. Applying the advances of precision medicine equitably to patients in resource-rich and low- and middle-income countries will be critical to impacting the survival of young adults with breast cancer worldwide.

Precision Medicine for Adolescent and Young Adult (AYA) Oncology.

Precision medicine, also referred to as "personalized medicine" is an approach in customizing disease prevention and treatment by integrating the unique differences found in individuals, typically identified through molecular or genomic characterization [...].

Sexual health outcomes among adolescent and young adult cancer patients: a systematic review and meta-analysis.

BACKGROUND: Sexual health outcomes (SHO), which entail the physical, emotional, mental, and social impacts, are an important consideration for adolescent and young adults (AYA, ages 15-39) affected by cancer. The objective of this systematic review and meta-analysis is to summarize the current literature and evaluate AYA cancer impact on SHO. METHODS: EMBASE and MEDLINE were searched from January 1, 2000 to September 28, 2022 to identify epidemiologic studies that used an analytic observational design, included individuals with AYA cancer and non-cancer control participants, and evaluated SHO. Odds ratios and prevalence ratios were calculated; random effects models were used to obtain pooled measures where possible. RESULTS: Of 2621 articles, 8 were included that investigated 23 SHO in 9038 AYA cancer patients. Based on the sexual response cycle, outcomes were categorized as those occurring among males (desire = 1, arousal = 1, orgasm = 4, other = 3) and females (desire = 2, arousal = 1, orgasm = 2, pain = 6, other = 3). It was feasible to conduct meta-analysis for 3 female SHO and 5 male SHO. There were associations between AYA cancer and 3 SHO: vaginal dryness (pooled odds ratio = 3.94; 95% confidence interval (CI) = 2.02 to 7.70), ejaculatory dysfunction (pooled odds ratio = 3.66; 95% CI = 2.20 to 6.08), and testosterone level (pooled mean difference = -2.56 nmol/liter; 95% CI = -3.46 to -1.66; P = .00001). CONCLUSION: This study found increased ejaculatory dysfunction and reduced testosterone levels in male AYA cancer patients and increased vaginal dryness in female AYA cancer patients, highlighting the need for sexual health resources in this population.

Variations in Emergency Service Utilization among Cancer Survivors: Results from the Pan-Canadian Experiences of Cancer Patients in Transition Study Survey.

Purpose: The objective of this study was to examine variations in emergency service utilization (ESU) among cancer survivors during the first year after completing primary cancer treatment. Methods: In 2016, the Canadian Partnership Against Cancer collected survey responses from cancer survivors across Canada about self-reported ESU after completing primary cancer treatment. We included survey respondents diagnosed with nonmetastatic breast, hematologic, colorectal, melanoma, or prostate cancer. Multivariable, multinomial logistic regression analysis was used to examine factors associated with cancer survivors' ESU. Results: Of the 5,774 cancer survivors included in our analysis, 22% reported ESU during the first year after completing their primary cancer treatment, 16% reported ESU one to three times, and 6% reported ESU more than three times. Factors significantly associated with frequent ESU included younger age, colorectal and hematologic cancers, more frequent primary care provider and oncology specialist visits, single or retired status, lower income, and self-reported lower quality of life. Conclusion: Our study identified factors associated with more frequent ESU among cancer survivors in the first year after completing primary cancer treatment. These factors highlight differences in cancer survivors' demographics, their ability to access and need for healthcare services, and the complexity of using ESU as a metric for quality improvement in survivorship care. These variations must be considered in quality improvement initiatives.

Reproductive Health Outcomes among Adolescent and Young Adult Cancer Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: This systematic review and meta-analysis (SRMA) aimed to synthesize the current literature on the impacts of adolescent and young adult (AYA, ages 15-39 years) cancer on reproductive health outcomes. METHODS: EMBASE and Medline were searched from 1 January 2000 to 26 January 2022 for observational studies that included individuals with AYA cancer and controls which evaluated reproductive health outcomes. We used random effects models and 95% confidence intervals to obtain pooled measures of associations between AYA cancer, cancer treatment, and reproductive health outcomes. RESULTS: The search identified 8625 articles; 21 were included. 62 reproductive outcomes were assessed and classified according to a sex-based framework as fetal/neonatal (n = 26), maternal (n = 11), fetal/neonatal-maternal (n = 23), and maternal-paternal (n = 2). Meta-analyses of crude estimates showed significant associations between AYA cancer and outcomes including preterm birth (pooled odds ratio [pOR] 1.31; 95% CI: 1.22, 1.42), gestational diabetes (pOR 1.43; 95% CI: 1.03, 1.99), and fertility treatment (pOR 2.66; 95% CI 1.71, 4.11). We also found higher odds of preterm birth (pOR 1.65; 95% CI: 1.21, 2.26) and low APGAR score at birth (pOR 2.03; 95% CI: 1.32, 3.13) among AYA cancer patients who received radiation compared to controls. CONCLUSIONS: Our SRMA quantified impacts of AYA cancers and treatments on several reproductive health outcomes.

The Effect of Specialized Palliative Care on End-of-Life Care Intensity in AYAs with Cancer.

CONTEXT: Many adolescents and young adults (AYAs; 15-39 years) with cancer receive high intensity (HI) care at the end of life (EOL). Palliative care (PC) involvement in this population is associated with lower risk of HI-EOL care. Whether this association differs by specialized vs. generalist PC (SPC, GPC) is unknown. OBJECTIVES: (1) To evaluate whether SPC had an impact on the intensity of EOL care received by AYAs with cancer; (2) to determine which subpopulations are at highest risk for reduced access to SPC. METHODS: A decedent cohort of AYAs with cancer who died between 2000-2017 in Ontario, Canada was identified using registry and population-based data. The primary composite measure of HI-EOL care included any of: intravenous chemotherapy <14 days from death; more than one ED visit, more than one hospitalization or any ICU admission <30 days from death. Physician's billing codes were used to define SPC and GPC involvement. RESULTS: Of 7122 AYA decedents, 2140 (30%) received SPC and 943 (13%) received GPC. AYAs who died in earlier years, those with hematologic malignancies, males and rural AYAs were least likely to receive SPC. No PC involvement was associated with higher odds of receiving HI-EOL care (odds ratio (OR) 1.5; P < 0.0001). SPC involvement was associated with the lowest risk of HI-EOL care (OR SPC vs. GPC 0.8; P = 0.007) and decreased odds of ICU admission (OR 0.7; P = 0.006). CONCLUSION: SPC involvement was associated with the lowest risk of HI-EOL care in AYAs with cancer. However, access to SPC remains a challenge.

Adolescent and young adult (AYA) oncology: A credentialed area of focused competence in Canada.

BACKGROUND: Adolescents and young adults (AYA, ages 15-39 years) affected by cancer have unique treatment, survivorship, and palliation concerns. Current oncology training does not focus on the distinctive needs of this demographic. Amid this recognition, the Canadian National AYA Cancer Task Force and Canadian Partnership Against Cancer have advocated the need for clinicians with formalized AYA experience. To address this need and standardize training, a national task force developed criteria for structured academic programs in AYA Oncology in Canada. METHODS: Workshops were organized to identify and establish the fundamentals of practice in AYA Oncology through consensus. These workshops followed the pre-existing rigorous process established by the Royal College of Physicians and Surgeons of Canada (Royal College) for new program development. The process includes: (i) developing the tasks associated with the discipline's practice, (ii) identifying the evidence trainees must provide to demonstrate tasks can be performed independently (the competence portfolio), (iii) developing training requirements and summarizing the knowledge, skills and attitudes required to perform these tasks, and (iv) identifying specific experiences essential to acquiring skills and demonstrating competent performance. RESULTS: AYA Oncology is a recognized an Area of Focused Competence (AFC) by the Royal College. CONCLUSION: The AFC designation in AYA Oncology provides a standardized curriculum, training experience and accreditation process to attract oncologists, promote expertise and advance AYA oncology care.

Perceptions and attitudes of medical oncologists regarding fertility preservation and pregnancy in high-risk cancer patients: A survey among Canadian medical oncologists.

PURPOSE: Infertility is a critical late toxicity that impacts adolescent and young adult (AYA, ages 15-39 years) cancer survivors. International oncology societies recommend discussing fertility preservation (FP) for all AYA patients, regardless of stage or prognosis. We aim to understand Canadian medical oncologists' perceptions, attitudes, and knowledge toward FP and pregnancy in patients with cancer, including advanced stages and high risk for recurrence. METHODS: An anonymous electronic survey utilizing hypothetical scenarios was sent to medical oncologists in the province of Ontario, Canada. Descriptive statistics were used to summarize all data. Logistic regression models were constructed to identify factors that predicted FP discussions and referrals. RESULTS: The survey was received by 91 medical oncologists, and the response rate was 44%. Fifty-eight percent of respondents offer FP for all patients. Physicians are more likely to refer patients for FP before curative intent therapy than before palliative chemotherapy (95% vs. 39.5%, p < 0.001). Most respondents (86%) are comfortable discussing FP; however, only 31% self-reported feeling up-to-date on knowledge of current FP methods. Female physicians were more likely to report up-to-date knowledge and confidence discussing FP with patients. Forty percent of respondents identified that concerns about the welfare of the resulting offspring should not be a cause for denying patients assistance in reproduction. CONCLUSION: There is a significant difference in physician attitude toward offering FP based on the cancer stage. Increased awareness of standard of care guidelines and resources for difficult situations may improve the frequency of discussions about FP in motivated cancer patients.

The physicAl aCtivity Counselling for young adult cancEr SurvivorS (ACCESS) trial: A protocol for a parallel, two-arm pilot randomized controlled trial.

BACKGROUND: Young adults aged 18-39 years commonly experience persistent side effects following cancer treatment that can impair their quality of life. Physical activity (PA) holds promise as a behavioral intervention to mitigate persistent side effects and improve quality of life. Yet, few young adults are active enough to incur these benefits and efforts to promote PA after cancer treatment ends are lacking. Therefore, we developed a novel theory-driven behavior change intervention to promote PA via videoconferencing technology in young adults who have completed cancer treatment, and are undertaking a pilot randomized controlled trial (RCT) to gather evidence to inform the design of a large, full-scale RCT. The specific aims of this parallel, two-arm pilot RCT are to: (1) assess intervention and trial protocol feasibility and acceptability; and (2) generate data on PA behavior. To promote transparency, improve reproducibility, and serve as a reference for forthcoming publication of results, we present the study protocol for this pilot RCT (version 7) within this paper. METHODS: Young adults who have completed cancer treatment are being recruited from across Canada. After informed consent is obtained and baseline assessments are completed, participants are randomized to the intervention group (i.e., a 12-week behavior change intervention delivered via videoconferencing technology by trained PA counsellors) or usual care group (i.e., no intervention). Several feasibility outcomes covering enrollment, allocation, follow-up, and analysis are tracked by study staff. Acceptability is assessed through interviews exploring participants' experiences, thoughts, and perspectives of the trial protocol (i.e., intervention and usual care groups), as well as participants' views of the intervention and its mode of delivery (i.e., intervention group only) and PA counsellors' experiences delivering the intervention. PA behavior is measured using accelerometers at baseline (pre-randomization), post-intervention, and at follow-up (24 weeks post-baseline). DISCUSSION: There are growing calls to develop interventions to support young adults' motivation to engage in PA and adopt an active lifestyle to improve their quality of life after cancer treatment ends. Real-time videoconferencing shows promise for disseminating behavior change interventions to young adults and addressing participation barriers. Considering the importance of establishing intervention and trial protocol feasibility and acceptability prior to evaluating intervention efficacy (or effectiveness), this pilot RCT is critical to understand how participants embrace, engage with, and complete the intervention and trial protocol. Indeed, these data will help to determine which refinements, if any, are required to the intervention and trial protocol (e.g., implementation approach, evaluation methods) prior to a large, full-scale RCT aiming to test the effects of the intervention on PA behavior. Additionally, the PA behavior data collected will be useful to inform the sample size calculation for a large, full-scale RCT. TRIAL REGISTRATION: The trial was registered with the ClinicalTrials.gov database (ID: NCT04163042) on November 14, 2019, prior to the start of the trial in February, 2021.

Factors influencing cancer survivors' experiences with follow-up cancer care: results from the pan-Canadian Experiences of Cancer Patients in Transition Study survey.

PURPOSE: The purpose of this study was to examine the influence of individual and structural factors on cancer survivors' experiences with follow-up cancer care. METHODS: In 2016, the Canadian Partnership Against Cancer collected survey responses from cancer survivors about their experiences with follow-up cancer care. We included respondents from this survey if they were diagnosed with non-metastatic breast, hematologic, colon, melanoma, and prostate cancer. Our primary outcome was cancer survivors' self-reported overall experience with follow-up cancer care. We used multivariable logistic regression to examine the influence of individual and structural factors on cancer survivors' experiences with follow-up cancer care. RESULTS: Of the 8402 cancer survivors included in our study, 81.8% (n = 6,875) reported a positive experience with their follow-up cancer care. The individual factors associated with positive overall experiences were more commonly those associated with self-perceptions of respondents' personal health and well-being rather than baseline sociodemographic factors, such as sex, income, or education. For example, respondents were more likely to report a positive experience if they perceived their quality of life as good (OR 1.9, 95% CI 1.0-3.5, p < 0.01) or reported not having an unmet practical concern (OR 1.3, 95% CI 1.1-1.6, p < 0.01). The structural factors most strongly associated with positive overall experiences included respondents perceiving their oncology specialist was in charge of their follow-up cancer care (OR 5.2, 95% CI 3.6-7.5, p < 0.01) and reporting the coordination of their follow-up cancer care among healthcare providers was good or very good (OR 8.4, 95% CI 6.7-10.6, p < 0.01). CONCLUSION: While real-world experiences with follow-up cancer care in Canada are reported to be positive by most cancer survivors included in this study, we found differences exist based on individual and structural factors. A better understanding of the reasons for these differences is required to guide the provision of high-quality follow-up care that is adapted to the needs and resources of individuals and contexts.

Clinical outcomes of brain metastasectomy from soft tissue and bone sarcomas: a systematic review.

BACKGROUND: Brain metastasis in sarcomas is associated with a poor prognosis. Data regarding prognostic factors and clinical outcomes of surgical resection of brain metastasis from sarcomas are limited. The objective of this systematic review was to evaluate survival outcomes post-brain metastasectomy for patients with soft tissue and bone sarcomas. METHODS: A systematic review was conducted examining survival outcomes among adults and children with soft tissue and bone sarcoma undergoing brain metastasectomy, in the English language from inception up to May 31, 2021. Two reviewers independently evaluated and screened the literature, extracted the data, and graded the included studies. The body of evidence was evaluated and graded according to the Newcastle-Ottawa Quality Assessment Scale for Cohort Studies and the Joanna Briggs Institute Critical Appraisal Checklist for Case Series. Results were synthesized using descriptive methods. A meta-analysis was not possible due to the low quality and heterogeneity of studies. RESULTS: Ten studies published between 1994 and 2020 were included: three were retrospective cohort studies and seven were case series. 507 patients were included, of whom 269 underwent brain metastasectomy. The median follow-up period ranged between 14 and 29 months. The median survival period after metastasectomy ranged from 7 to 25 months. The most common prognostic factors associated with survival included presenting performance status, age, number of brain metastases, presence of lung metastases, and peri-operative radiation therapy administration. DISCUSSION: Although the level of evidence is low, retrospective studies support that brain metastasectomy can be performed with reasonable post-operative survival in selected individuals.

Metastasectomy in Leiomyosarcoma: A Systematic Review and Pooled Survival Analysis.

This study assesses the survival in patients undergoing metastasectomy for leiomyosarcoma (LMS) and compares the outcomes by the site of metastasectomy. We conducted a systematic review and pooled survival analysis of patients undergoing metastasectomy for LMS. Survival was compared between sites of metastasectomy. We identified 23 studies including 573 patients undergoing metastasectomy for LMS. The pooled median survival was 59.6 months (95% CI 33.3 to 66.0). The pooled median survival was longest for lung metastasectomy (72.8 months 95% CI 63.0 to 82.5), followed by liver (34.8 months 95% CI 22.3 to 47.2), spine (14.1 months 95% CI 8.6 to 19.7), and brain (14 months 95% CI 6.7 to 21.3). Two studies compared the survival outcomes between patients who did, versus who did not undergo metastasectomy; both demonstrated a significantly improved survival with metastasectomy. We conclude that surgery is currently being utilized for LMS metastases to the lung, liver, spine, and brain with acceptable survival. Although low quality, comparative studies support a survival benefit with metastasectomy. In the absence of randomized studies, it is impossible to determine whether the survival benefit associated with metastasectomy is due to careful patient selection rather than a surgical advantage; limited data were included about patient selection.

Setting Priorities for a Provincial Adolescent and Young Adult Oncology Program.

Adolescent and young adult (AYA, ages 15-39 years) oncology patients are an underserved population with specialized needs. AYA programs are absent from most Canadian centers. We identified a priority list and sequence for new programs to address. Program goals, priorities, and activities were developed through literature review, national consensus documents, and expert opinion. Health care providers (HCPs) involved in AYA cancer care, administrators, and patient and family representatives were engaged to co-develop program goals and activities. A modified Delphi technique was used through two iterations followed by an in-person meeting to prioritize program implementation. Consensus was defined as a mean score of less than 2.0 (not important) or 4.0 or greater (important). Items without consensus (scored between 2.0 and 3.99) were discussed at the in-person meeting. Sixty provincial stakeholders completed the Delphi survey across multiple disciplines. Twenty-seven stakeholders attended the in-person meeting. All goals were deemed important, except development of a research program. Patient implementation tasks ranked highest. Priority sequence of implementation was: patient care first, followed by HCP education; patient and family education; program sustainability plan; evaluation; research; then a model for multidisciplinary tumor board review. These represent key goals for new AYA oncology programs and a priority sequence of implementation.

Metastasectomy in synovial sarcoma: A systematic review and meta-analysis.

BACKGROUND: Synovial sarcoma (SS) is a malignancy with high metastatic potential. The role of metastasectomy in SS is unclear, with limited data on prognostic factors and clinical outcomes. In this systematic review, we evaluate the survival outcomes post-metastasectomy for patients with SS. METHODS: A systematic review was undertaken following PRISMA guidelines. English studies reporting survival outcomes among adults and children with SS undergoing metastasectomy were evaluated. Databases were searched from inception to May 31, 2021, and included Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. Two reviewers independently undertook literature evaluation and screening, data extraction and grading of studies. Risk of bias assessments utilized the Newcastle-Ottawa Quality Assessment Scale for Cohort Studies and the Joanna Briggs Institute Critical Appraisal Checklist for Case Series. Qualitative data was summarized in descriptive format, and survival outcome data were assessed for meta-analysis. RESULTS: Thirteen retrospective studies, published between 1993 and 2017, were included, four were cohort studies, and nine were case series. A total of 598 patients with SS were included, of whom 462 had metastatic pulmonary disease, and 309 underwent metastasectomy. The median ages of the study cohorts ranged from 14 to 51 years. The median survival period after metastasectomy ranged from 21 to 80 months. Patients who underwent metastasectomy had a lower risk of mortality compared to those who did not (pooled HR 0.26 95% CI 0.14-0.49). The most common prognostic factors associated with survival included a disease-free interval of greater than 12 months and complete resection of the metastases. DISCUSSION: Although the level of evidence is low, retrospective studies support a clinical advantage for metastasectomy in selected patients with metastatic SS. FUNDING: This was not a funded study. REGISTRATION: This protocol has been registered within the international prospective register of systematic reviews (PROSPERO) database (registration ID: CRD42019126906).

Pre-medication protocols for the prevention of paclitaxel-induced infusion related reactions: a systematic review and meta-analysis.

BACKGROUND: Prophylaxis against infusion-related reactions (IRR) from paclitaxel with steroids and antihistamines is a standard of care due to high rates of IRR. This systematic review and meta-analysis aimed to comprehensively summarize the evidence behind various prophylaxis strategies. METHODS: EMBASE, MEDLINE, PubMed, and the Cochrane Register of Controlled Trials were searched (1946 to May 14, 2021). The primary outcomes were Grade 3/4 IRR and any-grade IRR. Secondary outcomes included treatment delay or discontinuation and adverse events secondary to pre-medications. RESULTS: Of the 1285 unique citations, 26 studies were selected: 11 studies for quantitative analysis and 15 studies for qualitative analysis. Studies included randomized controlled trials and observational studies (n = 25-281). There was a non-significant benefit in favour of oral steroids starting 12 h prior to paclitaxel administration versus intravenous steroids immediately prior to paclitaxel administration for grade 3/4 IRRs, with a risk difference (RD) of 2% [95%CI 0 to 5%], any-grade IRR with a RD of 4% [95%CI: -1% to 9%] and treatment discontinuation with a RD of 1% [95%CI -1% to 2%]. For de-escalation strategies, a point-estimate for any-grade IRR was 0.44% [95% CI, 0 to 0.02, p = 0.98] and for grade 3/4 IRR was 3.1% (95% CI, 0.02 to 0.07, p = 0.11). CONCLUSION: Although studies have high risk of bias and risk, differences between steroid routes of administration were small, there was a non-significant trend in favour of oral steroids. De-escalation strategies after two previous successful paclitaxel infusions have an overall low incidence rate of severe IRR and warrant further prospective clinical trials. Insufficient evidence remains to recommend for or against other interventions for the prevention of paclitaxel IRR.

Impact of Palliative Care Involvement on End-of-Life Care Patterns Among Adolescents and Young Adults With Cancer: A Population-Based Cohort Study.

PURPOSE: Evidence suggests that adolescents and young adults (AYAs) with cancer (defined as age 15-39 years) receive high-intensity (HI) medical care at the end-of-life (EOL). Previous population-level studies are limited and lack information on the impact of palliative care (PC) provision. We evaluated prevalence and predictors of HI-EOL care in AYAs with cancer in Ontario, Canada. A secondary aim was to evaluate the impact of PC physicians on the intensity of EOL care in AYAs. METHODS: A retrospective decedent cohort of AYAs with cancer who died between 2000 and 2017 in Ontario, Canada, was assembled using a provincial registry and linked to population-based health care data. On the basis of previous studies, the primary composite measure HI-EOL care included any of the following: intravenous chemotherapy < 14 days from death, more than one emergency department visit, and more than one hospitalization or intensive care unit admission < 30 days from death. Secondary measures included the most invasive (MI) EOL care (eg, mechanical ventilation < 14 days from death) and PC physician involvement. We determined predictors of outcomes using appropriate regression models. RESULTS: Of 7,122 AYAs, 43.8% experienced HI-EOL care. PC physician involvement (odds ratio [OR], 0.57; 95% CI, 0.51 to 0.63) and older age at death (OR, 0.60; 95% CI, 0.48 to 0.74) were associated with a lower risk of HI-EOL care. AYAs with hematologic malignancies were at highest risk for HI and MI-EOL care. PC physician involvement substantially reduced the odds of mechanical ventilation at EOL (OR, 0.36; 95% CI, 0.30 to 0.43). CONCLUSION: A large proportion of AYAs with cancer experience HI-EOL care. Our study provides strong evidence that PC physician involvement can help mitigate the risk of HI and MI-EOL care in AYAs with cancer.

Long-term impact of bone-modifying agents for the treatment of bone metastases: a systematic review.

PURPOSE: Bone-modifying agents (BMAs) for bone metastases are commonly prescribed for many years even though randomized clinical trials are only 1-2 years in duration. A systematic review on the risk-benefit of BMA use for > 2 years in breast cancer or castrate-resistant prostate cancer was conducted. METHODS: MEDLINE, Embase, and Cochrane databases were searched (1970-February 2019) for randomized and observational studies, and case series reporting on BMA efficacy (skeletal-related events and quality of life) and toxicity (osteonecrosis of the jaw, renal impairment, hypocalcemia, and atypical femoral fractures) beyond 2 years. RESULTS: Of 2107 citations, 64 studies were identified. Three prospective and 9 retrospective studies were eligible. Data beyond 2 years was limited to subgroup analyses in all studies. Only one study (n = 181) reported skeletal-related event rates based on bisphosphonate exposure, with decreased rates from 27.6% (0-24 months) to 15.5% (> 24 months). None reported on quality of life. All 12 studies (denosumab (n = 948), zoledronate (n = 1036), pamidronate (n = 163), pamidronate-zoledronate (n = 522), ibandronate (n = 118)) reported ≥ 1 toxicity outcome. Seven bisphosphonate studies (n = 1077) and one denosumab study (n = 948) reported on osteonecrosis of the jaw. Across three studies (n = 1236), osteonecrosis of the jaw incidence ranged from 1 to 4% in the first 2 years to 3.8-18% after 2 years. Clinically significant hypocalcemia ranged from 1 to 2%. Severe renal function decline was ≤ 3%. Atypical femoral fractures were rare. CONCLUSIONS: Evidence informing the use of BMA beyond 2 years is heterogeneous and based on retrospective analysis. Prospective randomized studies with greater emphasis on quality of life are needed. PROSPERO REGISTRATION NUMBER: CRD42019126813.

Young Adult Experience in an Outpatient Interdisciplinary Palliative Care Cancer Clinic.

PURPOSE: Young adults (YAs; defined as 18-39 years of age) with advanced cancer are a group for whom standardized age-appropriate palliative care has not been established. The purpose of this study was to explore the YA experience and perceptions of palliative care in an outpatient interdisciplinary palliative care clinic for this population. PATIENTS AND METHODS: Using an interpretive descriptive design, semistructured interviews were conducted with 12 YAs with advanced cancer who were being seen jointly by a palliative care physician and psychiatrist in an ambulatory palliative care clinic. Interviews explored participants' understanding and experiences of receiving palliative care. Six family members were also interviewed to build on the YA experience. Data collection and analysis occurred concurrently, drawing on the constructivist grounded theory method to analyze the data. RESULTS: Participants described being referred to and seen in the interdisciplinary palliative care clinic as a conflicting and at times difficult experience because of the feeling of being categorized as palliative as YAs. Even so, there were key aspects associated with the specific palliative care approach that allowed YAs to cope with this new label, leading to a beneficial experience, specifically: provided YAs with time and space to explore the experience of having cancer at a younger age, created repeat opportunities to talk openly with people who "got it," and highlighted the importance of including family support in the care of YAs. CONCLUSION: YAs who were referred to the interdisciplinary palliative care clinic struggled with the category of palliative care but also found the care they received beneficial. Findings provide an approach to palliative care tailored to YAs with advanced cancer.

Survival by histology among patients with bone and soft tissue sarcoma who undergo metastasectomy: protocol for a systematic review and meta-analysis.

BACKGROUND: Metastasectomy is performed on a select cohort of patients with advanced and/or recurrent bone and soft tissue sarcomas because of the potential for long term relapse free and overall survival associated with the procedure. However, the evidence supporting metastasectomy is difficult to summarize without a systematic examination of existing literature. The objective of this systematic review will be to examine survival among both adults and children with advanced and recurrent bone and STS who undergo metastasectomy. METHODS: We designed and registered a study protocol for a systematic review and meta-analysis. We will include data from survival studies (e.g., randomized trials, cohort studies, routine case registries, and case control) conducted in children and adults with advanced and recurrent bone and soft tissue sarcoma who undergo metastasectomy. The primary outcome will be overall survival. Secondary outcomes will be 30-day post-operative mortality, recurrence-free survival, time off systemic therapy, and patient-reported outcomes including quality of life end points where available. Literature searches will be performed in multiple electronic databases including Ovid MEDLINE ® (1946 to present), Ovid EMBASE (1974 to present), Web of Science, and Cochrane Library. Grey literature will be identified through searching references, conference abstracts, Papers First, and Google Scholar. Two investigators will independently screen all citations, full-text articles, and abstract data. Full-text articles selected for analysis will be assessed for quality and risk of bias. If feasible, we will conduct a random effects meta-analysis. Estimates will be stratified according to histology comparing survival based on organ of metastasectomy. Additional analysis will be conducted to explore the potential sources of heterogeneity according to various patient, disease, and treatment characteristics (e.g., metastasis status, age, disease burden, and concomitant interventions). DISCUSSION: This systematic review and meta-analysis will identify, evaluate, and integrate data on survival of metastasectomy of bone and soft tissue sarcoma by organ of metastasis. Our findings may have implications for clinicians, patients, and their families when considering selection for resection of oligometastatic disease in de novo, or recurrent bone and soft tissue sarcoma. Implications for future research will be identified to improve the outcomes of these complex patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019126906.