Adult Cancer Population Research Articles

Physical Comorbidities and Their Relationship with Cancer Treatment and Its Outcomes in Older Adult Populations: Systematic Review.

BackgroundCancer is one of the predominant causes of morbidity and mortality in older adult populations worldwide. Among a range of barriers, comorbidity particularly poses a clinical challenge in cancer diagnosis, prognosis, and treatment owing to its heterogeneous nature. While accurate comorbidity assessments and appropriate treatment administration can result in better patient outcomes, evidence related to older adult cancer populations is limited as these individuals are often excluded from regular clinical trials due to age and comorbid conditions.ObjectiveTo determine the prevalence of physical comorbidity and the impact of physical comorbidities and rurality on treatment and its outcomes in older adult cancer populations.MethodsScientific databases Embase and PubMed were searched for published scientific literature on physical comorbidity and older adult cancer patients. Google Scholar was searched for scholarly literature published in nonindexed journals. Snowballing was utilized to identify research papers missed in the above searches. Included studies : (1) reported on original research involving cancer patients; (2) included patients aged 65 years or older; (3) had patients receiving cancer-related treatment and (4) cancer survivors; (5) reported on physical comorbidity as a variable; (6) were published in English; and (7) conducted from any geographical location.ResultsIn total, 29 studies were selected for data extraction, evidence synthesis, and quality assessment. In these, comorbidities ranged from 37.9%-74.3% in colorectal cancer, 74%-81% in head and neck cancer, and 12.6%-49% in breast cancer. Moderate comorbidities ranged from 13%-72.9%, and severe comorbidities from 2.5%-68.2%. Comorbidity increased with age, with comorbidity affecting both treatment choice and process. Physical comorbidities significantly affected treatment initiation, causing delay, toxicity, and discontinuation. Older adult cancer patients were given less vigorous and nonstandard treatments and were also less likely to be offered treatment. Where patients are given more vigorous treatment, several studies showed better survival outcomes. Appropriate treatment in older adult cancer patients increased both overall and disease-related survival rates. None of the studies noted rurality as a distinct variable.ConclusionsThis systematic review concludes that there is evidence to substantiate the adverse effect of comorbidity on treatment and survival outcomes. However, the mechanism by which comorbidity impedes or impacts treatment is unknown in many cases. Some low-quality evidence is available for considering the functional status and biological age in treatment decisions. Future studies that substantiate the value of comprehensive older adult assessments before treatment initiation in cancer patients, including assessing the nature and severity of comorbidities, and additional consideration of rurality as a factor, could lessen the effect of comorbidities on the treatment process.

Understanding changes in substance use in the adolescent and young adult cancer population: a literature review

The nature of the risks involved in adolescents and young adults’ substance use has evolved considerably in the 21st century. While there has been a decline in the use of some substances such as alcohol, and changes in how substances such as nicotine and cannabis are consumed, the overall increase in substance use in this population has been driven by new psychoactive substances and nitrous oxide (laughing gas). However, adolescents and young adults with cancer are often reluctant to discuss their substance use with healthcare professionals, who often lack the knowledge, skills and time to engage with this complex and continually changing area.The authors undertook a narrative literature review on risk-taking behaviour involving substance use in adolescents and young adults, contextualising the main themes to adolescents and young adults with cancer. Healthcare professionals working with adolescents and young adults with cancer require improved evidence to understand the effect of substance use on treatment regimens, adherence to cancer therapy and the consequences for late effects. There is also a need for a wider appreciation of the effect that family, peers and social setting have on the nature and expression of substance use in this population.

Sleep-disordered breathing and risk of lung cancer: a meta-analysis longitudinal follow-up studies.

Consensus remains lack regarding whether sleep-disordered breathing (SDB) is an independent risk factor for lung cancer. We therefore conducted a meta-analysis to clarify the relationship of SDB and lung cancer. Longitudinal follow-up studies investigating the association between SDB and incidence of lung cancer were included by search of electronic databases including PubMed, Embase, and Cochrane's Library. A random-effects model was adopted to combine the results. Seven studies were included. Pooled results showed that presence of SDB was independently associated with higher incidence of lung cancer [adjusted risk ratio (RR): 1.28; 95% confidence interval (CI), 1.11-1.47; P < 0.001; I2 = 37%]. Sensitivity analysis limited to studies with adjustment of smoking showed consistent results (three studies, RR: 1.34; 95% CI, 1.22-1.48; P < 0.001; I2 = 8%). Subgroup analysis suggested that the association between SDB and higher risk of lung cancer was not significantly affected by study characteristics such as study design, source of population, sample size, evaluation methods for SDB, follow-up duration, methods for validation of lung cancer, or score of study quality (P values for subgroup difference all >0.05). No significant publication bias was observed (P for Egger's regression test = 0.258). These results suggested that SDB may be an independent risk factor of lung cancer in adult population. Intensive screening and prevention of lung cancer in subjects with SDB should be considered.

Structural Neuroimaging Findings Related to Adult Non-CNS Cancer and Treatment: Review, Integration, and Implications for Treatment of Cognitive Dysfunction.

Cancer- and treatment-related cognitive dysfunction (CRCD) is a common challenge faced by patients diagnosed with non-central nervous system (CNS) cancer. It has become increasingly recognized that multiple factors likely play a role in these symptoms, including the cancer disease process, systemic treatments (e.g., chemotherapy and endocrine therapies), and risk factors that may predispose an individual to both cancer and cognitive dysfunction. As the field has evolved, advanced neuroimaging techniques have been applied to better understand the neural correlates of CRCD. This review focuses on structural neuroimaging findings related to CRCD in adult non-CNS cancer populations, including examination of gray matter volume/density and white matter integrity differences between cancer patients and comparison groups, as well as emerging findings regarding structural network abnormalities. Overall, this literature has demonstrated consistent findings of reduced gray matter volume/density and white matter integrity in cancer patients relative to comparison groups. These are most prominent in individuals treated with chemotherapy, though alterations have also been noted in those treated with anti-estrogen and androgen-deprivation therapies. Alterations in gray and white matter structural network connectivity have also been identified. These structural abnormalities have been observed most prominently in frontal and temporal brain regions, and have been shown to correlate with subjective and objective cognitive function, as well as with physiological and clinical variables, helping to inform understanding of CRCD mechanisms. To date, however, structural neuroimaging techniques have not been utilized in systematic studies of potential CRCD treatments, suggesting a potentially fruitful avenue for future research.

Community-based exercise programs and cancer-related fatigue: a systematic review and meta-analysis.

To explore the prevalence of cancer-related fatigue (CRF) within community-based exercise programs and to determine the overall impact that participation in community-based exercise programs have on CRF. Literature searches were performed in March and updated in April of 2020. Studies that were community-based in adult cancer populations and reported CRF outcomes were included. Mean and standard deviations for CRF from 12 studies were extracted in order to compute a pooled effect size via a random effects model. An overall percentage was computed to discern how many community-based exercise programs reported CRF. Sample sizes varied among studies with most patients being middle-aged with breast cancer in the post-treatment setting. Most programs implemented aerobic + resistance exercise training interventions (~77%). Only ~42% of programs identified in the review reported CRF outcomes. The random effects model produced a pooled effect size of 0.30 (p < 0.001). Fewer than half of the identified community-based exercise programs reported CRF outcomes (~42%). Of those that did, the random effects model revealed a small yet significant impact on improving CRF after exercise participation, though more research is certainly needed in this area. This review produced promising preliminary evidence for the impact of community-based exercise programs on CRF. As exercise interventions transition to community-based facilities, patients should feel confident that these programs will continue to assist in managing CRF that is commonly experienced across the cancer continuum.

Impact of an at home exercise program in the pediatric, adolescent, and young adult cancer population newly diagnosed with acute lymphoblastic leukemia

Background: Over 30,000 cases of leukemia are diagnosed each year in the United States. For individuals ages 0-39, the one-year relative survival rate is 84.5%, and the 5-year survival is 94%. Improved survival rates come with long-term health challenges due to treatment, including cardiovascular disease, obesity, diabetes, fatigue, low quality of life (QOL), and reduced physical activity (PA). Current literature shows structured exercise in adult survivors can be beneficial for improving the long-term health effects resulting from treatment. Exercise induces the release of many growth factors into the bloodstream that aid in repair of the body following insult. Three factors specific to nerve damage is brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and Platelet-derived growth factor (PDGF). The benefits of exercise seen in adult survivors may translate to young survivors. We hypothesized that an 8-week at home exercise program in newly diagnosed acute lymphoblastic leukemia (ALL) patients (ages 5-25) would improve outcomes compared to baseline or a control group. The preliminary findings presented are based on the initial ten subjects and include physical, biomarker and self-reported outcomes. &#x0D; Experimental Methods: Newly diagnosed ALL patients were assigned to an 8-week at home exercise intervention during the consolidation phase of treatment. Fitbit activity tracker data and questionnaires were used for assessing adherence and feasibility. Blood samples were taken at baseline and at week eight. &#x0D; Results: Subjects were not able to complete over 75% of the exercise intervention; however, they did increase their overall physical activity and their neuropathy scores decreased compared to baseline. BDNF significantly increased in the control group, but not in the exercise group. &#x0D; Conclusion: The results indicate that an exercise program in this population during the consolidation phase may not be feasible. It also supports the association between neuropathy, physical activity, and BDNF levels after long term exercise.

Abstract PO-190: Prevalence and predictors of obesity-related cancers amongst racial/ethnic groups with metabolic syndrome

Abstract Background: Obesity-related cancer (ORC) accounts for 40% of all cancer diagnoses in the United States and are associated with higher amounts of body fat (BMI ≥25), which could increase the risk of developing cardiovascular disease (CVD). CVD remains the leading cause of death in cancer survivors and its associated risk tends to cluster into interrelated groups of conditions commonly known as the metabolic syndrome (MetS). Therefore, further insight on groups at risk for developing CVD within the ORC and MetS population is warranted. Previous studies identified the prevalence of ORC to be higher in non-Hispanic Blacks and Hispanics compared to non-Hispanic Whites. However, prior studies did not control for sociodemographic and lifestyle factors that can differ across race/ethnicity. The purpose of this study was to compare the prevalence of ORCs by race/ethnicity among the adult (&amp;gt;18) cancer population with MetS represented in the 1999-2014 NHANES Survey and to identify predictors associated with having an ORC among adults with MetS. Methods: MetS was defined using the National Cholesterol Education Program (NCEP) Adult Treatment Panel-III (ATP-III) guidelines. Cancer type was self-reported and further classified as ORC or non-ORC. A chi-square test was performed to determine prevalent differences in ORC between Non-Hispanic White, Non-Hispanic Black, and Hispanic participants with comorbid cancer and MetS. A multivariate logistic regression was utilized to evaluate predictors (race, sex, income, insurance, education, marital status, and smoking status) of ORC among adults with comorbid cancer and MetS. Results. Of the 1,554 adults with MetS, the prevalence of ORC was 30.6% in non-Hispanic Whites, 51.3% in non-Hispanic Blacks, and 54.1% in Hispanics (p=&amp;lt;0.001). Three of the eight predictors were significantly associated with ORC. For every one-year unit increase in age, the odds of ORC increased by 3% [95% CI (1.00- 1.05), p=&amp;lt;0.01]. Females were 6.27 times more likely to have an ORC compared to males [(95% CI (4.95-14.11), p= &amp;lt;0.0001]. Lastly, when compared to non-Hispanic Whites, Non-Hispanic Blacks were 2.1 times more likely to have an ORC [(95% CI (1.40-3.38) p= &amp;lt;0.001]; and Hispanics were 2.5 times more likely [(95% CI (1.39-4.77), p=&amp;lt;0.01]. All other factors were insignificant. Conclusions. Among NHANES participants with MetS, the prevalence of ORCs was significantly higher in Blacks and Hispanics compared to Whites. In addition, ORC risk was reduced for males and younger adults with MetS. Future studies on the long-term impact of MetS on persons with ORC by race/ethnicity are warranted. Citation Format: Shanada Monestime. Prevalence and predictors of obesity-related cancers amongst racial/ethnic groups with metabolic syndrome [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-190.

Mutation profile differences in younger and older patients with advanced breast cancer using circulating tumor DNA (ctDNA).

Little is known regarding the mutation profiles of ctDNA in the older adult breast cancer population. The objective of this study is to assess differences in mutation profiles in the older adult breast cancer population using a ctDNA assay as well as assess utilization of testing results. Patients with advanced breast cancer underwent molecular profiling using a plasma-based ctDNA NGS assay (Guardant360) between 5/2015 and 10/2019 at Siteman Cancer Center. The profiling results of a multi-institutionaldatabase of patients with advanced breast cancer who had undergone molecular profiling were obtained. Associations between mutations and age group (≥ 65 vs. < 65) were examined using a Fisher's exact test. In the single-institutional cohort, 148 patients (69.2%) were < 65years old and 66 patients (30.8%) ≥ 65years old. ATM, BRAF, and PIK3CA mutations were found more frequently in older patients with ER + HER2- breast cancers (p < 0.01). In the multi-institutionalcohort, 5367 (61.1%) were < 65years old and 3417 (38.9%) ≥ 65years old. ATM, PIK3CA, and TP53 mutations were more common in the older cohort (p < 0.0001) and MYC and GATA3 mutations were less common in the older cohort (p < 0.0001). CtDNA testing influenced next-line treatment management in 40 (19.8%) patients in the single-institutional cohort. When controlling for subtype, results from a single institution were similar to themulti-institutional cohort showing that ATM and PIK3CA were more common in older adults. These data suggest there may be additional molecular differences in older adults with advanced breast cancers.

Exploring the reasons cancer survivors do not seek help for their concerns: a descriptive content analysis

PurposeTo understand reasons why adult cancer survivors do not seek assistance as they transition from the end of cancer treatment to follow-up care. Understanding these reasons should inform survivorship care,...

Abstract A05: Incidence and trends in head and neck cancer among United States’ pediatric, adolescent, and young adult population

Abstract Objectives: In 2009, there were 48,010 new cases of head and neck cancer in the United States. A decade later, it is projected that there will be 65,410 new cases in 2019, a 36% increase in new cases of the disease. While this number represents the general head and neck cancer population in the United States, only a few studies have described incidence and trends in head and neck cancer in the pediatric, adolescent, and young adult population—individuals who may have to live with the effects of cancer treatment due to a younger than average age of diagnosis. This study aimed to estimate head and neck cancer incidence and trends in the United States’ pediatric, adolescent, and young adult population. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) 9 database from 1975-2016, we analyzed age-adjusted head and neck cancer incidence rates for pediatric cases (aged 0 to 14 years) and young adult cases (aged 15-39 years). We used Joinpoint regression analyses to examine incidence trends stratified by sex (male, female), race (white, blacks, and Others), and age groups (0-14, and 15-39 years). Results: There were 424 pediatric HNC cases and 6,936 adolescent and young adult cases in the study. Whites accounted for 70.6% of cancers, and 57.6% of cancers occurred in males. Overall, there was a 14.7% decrease in the incidence of HNC (1.32 per 100,000 in 1975 vs. 1.12 per 100,000 in 2016). For pediatric cases, there was a 51.2% decrease in incidence of HNC (0.18 per 100,000 in 1975 vs. 0.09 per 100,000 in 2016); in young adults, there was a 12.8% decrease in incidence of HNC (2.01 per 100,000 in 1975 vs. 1.75 per 100,000 in 2016). While there was overall decrease in incidence, we found differences based on sex. Among young adult males, the annual percent change (APC) from 1975 to 2016 was -0.46 (p &amp;lt; 0.05) while among young adult females, it significantly increased by 0.50 (p &amp;lt; 0.05). This difference in young adult male vs. female head and neck cancer incidence may have been driven by race: as stratified by race, the APC for white young adult males was -0.29 (ns) while white females had an APC of 0.55 (p &amp;lt; 0.05); and among black young adults, APC for males was -2.24 (p &amp;lt; 0.05) and APC for females was -0.82 (p &amp;lt; 0.05). Conclusions: Among pediatric, adolescent, and young adults in the United States, head and neck cancer has decreased markedly in all groups in the last four decades, except among white female adolescents and young adults where there has been a significant increase in the time period of the study. As this trend differs from the adult head and neck cancer population, it is critical that further investigations provide more insight into the epidemiology of head and neck cancer among white adolescent and young adult females. Note: This abstract was not presented at the conference. Citation Format: Nosayaba Osazuwa-Peters, Kara M. Christopher, Matthew C. Simpson, Premal B. Desai, Rebecca L. Rohde, Sai D. Challapalli, Adnan S. Hussaini, Neelima Panth, Eric Adjei Boakye. Incidence and trends in head and neck cancer among United States’ pediatric, adolescent, and young adult population [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A05.

Mutation profile differences in younger and older patients with advanced breast cancer using circulating tumor DNA (ctDNA).

1089 Background: Although the noninvasive nature of ctDNA testing is attractive in an older adult population, less is known regarding the mutation profiles of ctDNA in the older adult breast cancer population as this population is often excluded from studies. Previous tissue testing has shown differences in mutation profiles between older and younger adults with breast cancer. The objective of this study is to assess differences in mutation profiles in the older and younger adult breast cancer population using a ctDNA assay. Methods: Patients (pts) with advanced breast cancer underwent molecular profiling using a plasma-based ctDNA NGS assay (Guardant360) between 5/2015-10/2019 at Siteman Cancer Center. Clinicopathological histories were obtained from the medical record. The results of a multicenter database of pts with advanced breast cancer who had undergone molecular profiling using Guardant360 were obtained. Associations between mutations and age were measured using a Fisher’s exact test. Results: In the single institution cohort, of the 214 patients who underwent testing, 148 (69.16%) were &lt; 65 and 66 (30.84%) ≥ 65 years-old. The most frequently mutated genes in age &lt; 65 pts were TP53 (48.65%), PIK3CA (35.81%), and ESR1 (30.41%) while the most frequently mutated genes in age≥65 pts were PIK3CA (56.06%), TP53 (51.52%), ESR1 (25.76%), and ATM (21.21%). ATM, BRAF and PIK3CA mutations were found more frequently in age≥ 65 pts with ER+ HER2- breast tumors (p &lt; 0.01). MYC and ESR1 mutations were not significantly associated with age, overall or within subtype. Overall ctDNA resulted in change in management in 19.8% pts (40/202). In the larger multicenter cohort, of the 8803 pts who underwent testing, 5367 (61.0%) were &lt; 65 and 3417 (38.8%) ≥ 65 years-old. ATM, ESR1 and PIK3CA mutations were more common in age≥65 pts (p &lt; 0.0001) and MYC mutations were less common in age≥65 pts (p &lt; 0.0001). Conclusions: This study found that ctDNA is a feasible, attractive alternative to traditional biopsies and may identify actionable mutations in older adults with breast cancer. When controlling for subtype, results from a single institution were similar to the larger multicenter cohort showing ATM and PIK3CA were more common in the older adult population. This data suggests there may be additional molecular differences between breast cancer in older compared to younger adults that warrants further investigation.

Cancer survivor’s perspectives on the major challenge in the transition to survivorship

ObjectivesTo understand cancer survivors’ perspectives regarding the major challenge in transitioning from cancer treatment to follow-up care. Identification of major issues should inform survivorship care and help reduce suffering. MethodsA national survey was conducted to identify experiences with follow-up for cancer survivors one to three years post-treatment. The survey included open-ended questions for respondents to add topics of importance and details that offer deeper insight into their experiences. This publication presents analysis of the open-ended question about the major challenge faced by adult cancer population. ResultsOf 13,534 unique adult survey respondents, 8706 respondents identified major challenges. Of those reporting challenges, 4727 (54.3 %) named a single challenge but 3979 (45.7 %) identified more than one. In total, 15,351 challenges were identified. Responses to open-ended questions are summarized under significant themes: major concerns are often more than singular issues; recovery and fear of recurrence; and information needs. Conclusions and practice implicationsResults indicate significant numbers of adult survivors have multiple concerns about physical, emotional, and practical issues but are not receiving assistance and/or appropriate information to help manage these concerns. It is important to determine how health care can be proactive in identifying and addressing needs of survivors.

Cognitive Mechanisms in Adolescent and Young Adult Cancer Patients and Survivors: Feasibility and Preliminary Insights from the Cognitions and Affect in Cancer Resiliency Study.

This cross sectional pilot study assesses the feasibility of conducting online research into cognitive mechanisms in adolescent and young adult cancer populations. Twenty-one participants, aged 18-39 years, answered questionnaires about mental defeat, rumination, cancer worry, anxiety, and experience participating in such research. Seven participants scored in the clinical range for anxiety. Cancer-related worry was common. Rumination and mental defeat were positively associated with anxiety. The participants reported the length and type of questions to be appropriate and not distressing. Findings may inform future research into cognitive mechanisms, which could aid the development of psychosocial interventions for young cancer patients.

Comparison of Health Outcomes in Adolescent and Young Adults (AYA) Oncology Patients Treated at a Pediatric Versus Adult Institute

BACKGROUND Overall survival for adolescent and young adult (AYA) cancer population, ages 15 to 39 years, demonstrated minimal improvement during the last several decades. Potential factors influencing inferior outcomes within this group include the complex biology of AYA cancers, lower rates of clinical trial enrollment, the significant toxicities caused by therapies, and unmet psychosocial needs. AYA patients can often be treated in either pediatric or adult institutions. The type of institution where they receive treatment is influenced by age, type of cancer, and distance from a pediatric oncology center. There are concerns that differences in care between pediatric and adult treatment settings are influencing the slow progress in improving outcomes. Acute care utilization might reflect the burden of toxicities and access to care, which might vary based on treatment setting. There is limited research suggesting that AYAs treated at pediatric institutes are more likely to be enrolled in clinical trials. The AYA population also has challenging psychosocial needs and it is unknown if there is a difference in how those needs are addressed in different treatment settings. The objective of this study was to examine whether there are differences in clinical trial enrollment, acute care utilization, and psychosocial support between AYA oncology patients treated at a pediatric versus an adult facility. Our hypothesis was that AYAs treated at a pediatric facility will have increased enrollment in clinical trials, less acute care utilization, and more psychosocial referrals compared to AYAs treated at an adult facility. METHODS We conducted a retrospective cohort study of patients ages of 15 to 39 years who were diagnosed with a hematologic malignancy (acute lymphoblastic leukemia (ALL), acute myelocytic leukemia (AML), Hodgkin lymphoma (HL) and Non-Hodgkin Lymphoma (NHL)) and were cared for at a pediatric or adult facility during the years 2013-2017. The primary health outcomes examined were acute care utilization and psychosocial resources utilized, based on a patient's exposure time (defined as one year from diagnosis or 1 month after completion of therapy, whichever came first). Data were analyzed using SAS 9.4. To compare the health outcomes between patients treated at the two facilities, the Chi-square test or Fisher's exact test was used for categorical variables. For continuous variables, due to the skewness of the data, a log transformation was applied to the length of stay (LOS) variable, and then the Student's t-test was used. The Mann-Whitney test was used for the other continuous variables. This study was approved by the Children's Hospital of Wisconsin Institutional Review Board. RESULTS A total of 196 patients were treated as either newly diagnosed or relapse/progressive patients who received care at the pediatric or adult treatment facilities. Leukemia patients treated at a pediatric facility were more likely to be enrolled on a clinical trial than patients treated at an adult facility (84% vs 22%, p&lt;0.0001). There was no statistically significant difference in enrollment in clinical trials for lymphoma patients at both treatment facilities (4% vs 8%, p=0.68) as shown in Table 1. There was no significant difference in acute care utilization for ED visits or inpatient hospitalizations for all diagnoses for the pediatric and adult facilities. Both ALL and HL patients had more ICU admissions per month at the pediatric facility compared to the adult facility (ALL: mean 0.25 vs 0.05, p=0.021; HL: mean 0.03 vs 0, p=0.0027). ALL and HL patients had longer hospitalization LOS at the adult facility (ALL p=0.020, HL p=0.014) There were more referrals for psychology, social work or case management and palliative care in the pediatric versus adult facility (p&lt;0.0001, p=0.011, p&lt;0.0001, respectively). CONCLUSION For AYA patients treated at a pediatric institute, leukemia patients have higher rates of clinical trial enrollment and all patients receive more psychosocial support compared to AYA patients treated at an adult institute. There was no difference in acute care utilization for ED visits or hospitalizations between patients treated at a pediatric or an adult facility. Patients with ALL and HL have more ICU admissions but overall shorter hospital LOS at the pediatric institution. Further work to determine the impact of these findings on the long-term outcomes and survival of AYA patients is needed. Disclosures Panepinto: NIH: Research Funding.

Elimination of Acute GvHD with Three Doses of Abatacept Prophylaxis Combined with Post-Transplant Cyclophosphamide after Myeloablative Treosulfan-Based Conditioning in the HLA Identical Sibling and Unrelated (10-12/12) Peripheral Blood Stem Cell Donor Setting: Improved Safety and Efficacy Compared to Alemtuzumab Prophylaxis

Background. Acute graft versus host disease (GvHD) remains a major cause of treatment failure post allogeneic stem cell transplantation (HSCT). CD28-CD80/CD86 axis T cell co-stimulation blockade with CTLA4-Ig using abatacept (AB) is an emerging acute GvHD prophylaxis strategy1. After myeloablative conditioning (MAC), together with methotrexate and calcineurin inhibition, four doses of AB commencing day (d)-1 is being investigated in the unrelated HLA 7/8 and 8/8 mismatched/matched donor settings, mostly in children2. It is unknown if AB can be de-escalated in adults to three doses for HLA matched sibling (SIB) or unrelated 10-12/12 donors (MUD), or combined with post-transplant cyclophosphamide (PT-CY) GvHD prophylaxis3, or combined with treosulfan (TREO)-based MAC4, which are other emerging transplant strategies. We investigated the safety and efficacy of this combination, and compared outcomes to a standard anti-CD52 directed IgG1 alemtuzumab (CH) prophylaxis regimen5 in a reduced intensity conditioning (RIC). Methods. We report a single centre consecutive cohort study using peripheral blood stem cells from SIB or HLA 10-12/12 MUDs, for HSCT in adults with blood cancer indications (intuitional registration: 1920-31). One group received AB GvHD prophylaxis while the other group received CH. During 2018-2019, the AB cohort received MAC with IV fludarabine 150 mg/m2, IV TREO 42 mg/m2, and 2 Gy total body irradiation (TBI). GvHD prophylaxis comprised three doses of IV AB 10 mg/kg on d+5, +14, and +28. This was combined with IV PT-CY 50 mg/kg on d+3 and +4, IV tacrolimus 0.03 mg/kg/d infusion from d+5, and IV mycophenolate mofetil 15 mg/kg tds from d+53. The MAC AB cohort was compared to a RIC CH cohort, chosen to be biased against AB. During 2017-2018 the CH cohort received RIC with IV fludarabine 150 mg/m2and IV melphalan 140 mg/m2. GvHD prophylaxis comprised IV CH 10 mg on d-7 to d-3, and IV ciclosporin 1.5 mg/kg bd from d-1. The primary outcome measure was the incidence of acute GvHD6 at d100 and 180 post HSCT. Secondary outcomes measures were the incidence of graft failure, mixed donor chimerism, donor lymphocyte infusion (DLI), CMV reactivation, relapse, overall survival, at d100 and 180. The AB and CH cohorts were indirectly compared. Results. A total of 39 patients were included in this study, with 15 consecutive patients in the AB group (Table). The AB group had a median Karnofsky score of 70% and HCT-CI of 6; significant comorbidity greater than other reports1,2. The major cancer indications were acute leukaemia and myelodysplastic syndrome (MDS). The AB and CH groups were largely balanced. There were no AB related infusion reactions. As expected for MAC, the AB group had a numerically but not clinically significantly slower time to engraftment relative to the RIC CH group. There was no AB group graft failure. Remarkably, the AB group did not experience acute GvHD compared to the CH group by d100 (P=0.03) and d180 (P&lt;0.01). In contrast, by d100, 29% in the CH group experienced acute GvHD after a median of 59 days post HSCT. No AB group patients experienced mixed donor chimerism (P&lt;0.01), nor required a DLI (P&lt;0.01) compared to the CH group, where all had &lt;99% T cell or whole blood values at d100. Consequently, 45% of the CH cohort without acute GvHD were treated with DLI, with all patients experiencing acute GvHD at a median of 39 days post DLI (Table). Other secondary outcomes were similar. The AB group experienced a CMV reactivation rate of 67% in IgG seropositive patients. Unfortunately, 93% of CMV IgG positive patients in the CH group experienced CMV reactivation. No relapses were observed by d180 in the AB group, whereas in the CH group, 8% of patients experienced relapse. Mortality at d180 was 20% in the MAC AB group, and 21% in the RIC CH group. Conclusions. Acute GvHD prophylaxis with only three doses of AB and PT-CY post TREO-based MAC appears to be safe and efficacious in the SIB and MUD settings, in a highly co-morbid adult blood cancer population. This AB approach seems favourable compared to CH despite RIC, where acute GvHD without DLI or post DLI remains significant. A prospective multicentre clinical trial with AB in this setting seems warranted to confirm these remarkable findings of patient benefit. References. 1. Biol Blood Marrow Transplant (BBMT) 2013;19:1638-49. 2. NCT01743131. 3. Lancet Haematol 2019;6:e132-43. 4. Cancer 2017;123:2671‐79. 5. BBMT 2017;23:805-12. 6. BBMT 2016;22:4-10. Table Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Abatacept, alemtuzumab, cyclophosphamide all the for the indication of graft versus host disease (GvHD) prophylaxis.

Methodological Issues in Psychosocial Research in Adolescent and Young Adult Cancer Populations.

Methodological Issues in Psychosocial Research in Adolescent and Young Adult Cancer Populations.

Preferences Regarding End-of-Life Care Among Adolescents and Young Adults With Cancer: Results From a Comprehensive Multicenter Survey in Japan

ContextPatient preferences influence end-of-life (EOL) care which patients receive. However, preferences regarding EOL care among adolescent and young adult (AYA) cancer population remain unclear. ObjectivesThe objective of the study was to evaluate preferences regarding EOL care among AYA cancer population. MethodsWe evaluated preferences regarding EOL care as a part of a comprehensive multicenter questionnaire study investigating the experience and needs of Japanese AYA cancer population. ResultsA total of 349 AYA cancer population (213 AYA cancer patients and 136 AYA cancer survivors) were evaluated. Eighty-six percent (296/344), 53% (180/338), 88% (301/341), and 61% (207/342) of participants with valid response preferred to have prognostic disclosure, receive palliative chemotherapy for incurable cancer with limited efficacy at the expense of considerable toxicity, actively use palliative care, and stay home at EOL, respectively. In multivariate analysis, the preference regarding prognostic disclosure was associated positively with no child status (odds ratio [OR] = 3.05, P = 0.003) and negatively with history of chemotherapy (OR = 0.23, P = 0.009), the preference regarding palliative chemotherapy for incurable cancer with limited efficacy at the expense of considerable toxicity was associated positively with status under active cancer treatment (OR = 1.74, P = 0.03), and the preference of staying home at EOL was positively associated with anxiety (OR = 1.72, P = 0.04). ConclusionThis study elucidated preferences regarding EOL care among Japanese AYA cancer population. These findings may help health care practitioners to have better understanding of preferences regarding EOL care among this population.

Fear of cancer recurrence in adolescent and young adult cancer survivors: A systematic review of the literature.

The current systematic review aims to provide an overview of fear of cancer recurrence (FCR) in adolescent and young adult cancer survivors (15-39years at cancer diagnosis, AYAs). MEDLINE, PubMed, PsycINFO, and Embase databases were independently searched to identify relevant quantitative articles. PRISMA systematic review procedures were followed with quality assessment. Seventeen studies were included in the current review. All were quantitative studies that utilized a cross-sectional study design. Seven articles reported results of FCR prevalence, six studied determinants related to FCR, and 11 articles provided information about consequences of FCR. Prevalence of FCR ranged from 31% to 85.2% among AYA survivors. Associations between sociodemographic/clinical variables and FCR were inconsistent. Psychological distress and higher treatment intensity were positively associated with higher FCR levels. Lower scores on levels of physical, psychological functioning, and overall health-related quality of life (QoL) were identified as consequences of increased FCR. FCR appears to be a prevalent concern among adolescent and young adult cancer populations. Adequate assessment to determine need for support and intervention is still required. Longitudinal studies in AYAs are warranted to understand the development and potential influence of FCR. Age-appropriate and flexible psychological care would be more successful potentially with this crucial background information.

The prevalence of germline DICER1 pathogenic variation in cancer populations.

BackgroundThe DICER1 syndrome is an autosomal dominant tumor‐predisposition disorder associated with pleuropulmonary blastoma, a rare pediatric lung cancer. Somatic missense variation in “hotspot” codons in the RNaseIIIb domain (E1705, D1709, G1809, D1810, E1813) is observed in DICER1‐associated tumors. Previously, we found the prevalence of germline pathogenic DICER1 variation in the general population is 1:10,600. In this study, we investigated the prevalence of pathogenic DICER1 germline variation in The Cancer Genome Atlas (TCGA; 32 adult cancer types; 9,173 exomes) and the Therapeutically Applicable Research to Generate Effective Treatment (TARGET; two pediatric cancer types; 175 exomes) cohorts.MethodsAll datasets were annotated and binned into four categories: pathogenic, likely pathogenic, variant of unknown significance, or likely benign.ResultsThe prevalence of DICER1 pathogenic variants was 1:4,600 in TCGA. A single participant with a uterine corpus endometrial carcinoma harbored two pathogenic germline DICER1 (hotspot and splice‐donor) variants, and a single participant with a rectal adenocarcinoma harbored a germline DICER1 stop‐gained variant. In the smaller TARGET dataset, we observed no pathogenic germline variants.ConclusionThis is the largest comprehensive analysis of DICER1 pathogenic variation in adult and pediatric cancer populations using publicly available data. The observation of germline DICER1 variation with uterine corpus endometrial carcinoma merits additional investigation.

Incidence and attributes of chemotherapy induced myelotoxicity, anemia and neutropenia in adults with cancer in Nepal: A cross-sectional observational study.

Myelosuppression remains a major toxicity in cancer patients receiving chemotherapy, and is associated with considerable morbidity, mortality and cost. The present study aims to investigate the prevalence and incidence of myelotoxicity, anemia and neutropenia in the adult cancer population, and further to determine the factors influencing them. This was a cross-sectional observational study conducted at National Academy of Medical Sciences, Bir Hospital, Kathmandu. A total of 170 subjects eligible for the study were enrolled for analysis. Prevalence and incidence of myelotoxicity anemia, neutropenia and myelotoxicity at enrollment and during study were investigated. Factors influencing development of myelotoxic event were determined. Of 170 enrolled patients, the prevalence of myelotoxicity, anemia and neutropenia at enrolment was 54 (31.8%), 20 (11.8%) and 28 (16.6%), respectively, with 27 (16%) mild and 12 (7.1%) moderate type of anemia. Incidence of myelotoxicity, anemia and neutropenia during treatment was 90 (52.94%), 44 (26%) and 53 (31.2%) respectively, with 70 (41.2%) mild, 39 (22.9%) moderate and 5 (2.9%) severe type of anemia. Age (OR: 0.49; p < 0.047), and baseline Hb (OR: 1.29; p < 0.01) were found to be independent predictors associated with anemia. Hb (OR: 2.42, CI: 1.79-3.28; p < 0.001) and smoking (OR: 0.49: p = 0.03) were found to be independent factors associated myelotoxicity. Our study confirmed a high incidence rate of myelotoxicity, neutropenia and anemia in a considerable number of Nepalese cancer patients receiving chemotherapy, and that baseline Hb, smoker and older adults are at more risk, these patients should be evaluated carefully and a prophylactic measure should be adopted accordingly so as to prevent toxicity and improve quality of life during cancer treatment.