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1.
JCO Oncol Pract ; : OP2000907, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33596114

RESUMO

PURPOSE: Our objective was to measure the trajectory of financial distress and to determine its relationship with quality of life (QOL) among patients with cancer. MATERIALS AND METHODS: We conducted a longitudinal survey of patients with gynecologic cancer starting a new line of systemic therapy at baseline, 3 months, and 6 months. Financial distress was measured using a Comprehensive Score for Financial Toxicity (COST) < 26, and QOL was measured using Functional Assessment of Cancer Therapy-General (FACT-G) with lower scores indicating worse responses. One-way repeated analysis of variances, generalized estimating equation models, and correlation coefficients were used to evaluate financial distress and QOL over time. RESULTS: There were 90 of 121 (74%) baseline participants with a 6-month follow-up. The average age was 60 years, 29% were African-American, 57% had an annual income < $40,000 in US dollars, and 6% were uninsured. At baseline, 54% of patients screened positive for financial distress, which was unchanged at 3 months (50%, P = .27) but decreased at 6 months (46%, P = .04) compared with baseline. There was no change in average COST (23.6, 25.1, 25.6; P = .33) or FACT-G (70.8, 71.0, 72.8; P = .68) over time. Less financial distress was moderately correlated with better QOL (r = 0.63, 0.61, 0.60) at each time point. The presence of financial distress was associated with a 16-point decrease in FACT-G QOL score over time. CONCLUSION: Upfront screening with COST identified 90% of patients who experienced financial distress, and COST did not change significantly over time. More severe financial distress was moderately correlated with worse QOL, and its presence was associated with a clinically meaningful 16-point decrease in QOL.

2.
J Cancer Surviv ; 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33547560

RESUMO

BACKGROUND: Young adult cancer survivors are at risk for subsequent human papillomavirus (HPV)-related malignancies. High-risk sexual behavior increases risk for HPV acquisition; HPV vaccination protects against infection. We aimed to determine the prevalence of sexual behaviors, factors related to high-risk sexual behaviors, and the relationship between sexual behaviors and HPV vaccine non-initiation among survivors. METHODS: Survivors at comprehensive cancer centers, aged 18-26 years and 1-5 years post-treatment, reported sexual behaviors and HPV vaccine initiation (i.e., ≥ 1 dose). Multivariable logistic regression was performed to calculate odds ratios (OR) and 95% confidence intervals (95%CI) for factors associated with high-risk sexual behaviors (age at first intercourse < 16 years, ≥ 3 lifetime sexual partners, or condom use ≤ 50% of the time) and to explore the relationship between sexual behaviors and vaccine non-initiation. RESULTS: Of the 312 participants (48.1% female, median age at cancer diagnosis 17.2 years and at survey 20.9 years), sexual intercourse was reported by 63.1%. Of those reporting intercourse, 74.6% reported high-risk sexual behavior. Factors related to high-risk sexual behavior included currently dating/partnered (OR = 4.39, 95%CI 2.5-7.7, P < 0.001) and perceived susceptibility to HPV (OR = 1.76, 95%CI 1.3-2.5, P < 0.001). Most survivors (75.3%) reported HPV vaccine non-initiation; sexual behaviors were not associated with vaccine non-initiation (P = 0.4). CONCLUSIONS: Many survivors participate in high-risk sexual behaviors, yet HPV vaccine initiation rates are low. Factors related to high-risk sexual behaviors can inform interventions to reduce risk for HPV acquisition among survivors. IMPLICATIONS FOR CANCER SURVIVORS: Cancer survivors participate in sexual behaviors that increase risk for HPV acquisition and would benefit from vaccination.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33420395

RESUMO

Mortality is highest in the first year following an allogeneic hematopoietic stem cell transplant. With recent advancements, we have expanded the pool of patients to whom we are able to offer transplant as a treatment option. In this context, we analyzed socioeconomic, patient, disease and transplant-related variables that predicted for 1-year all-cause, relapse-related (RRM) and non-relapse related mortality (NRM) in 304 patients at the University of Alabama at Birmingham. The 1-year overall survival, RRM and NRM rates were 60.5%, 13.5% and 22.7% respectively. A KPS score < 80, pre-transplant infection and hypertension and non-complete remission disease status adversely effected all-cause mortality. For NRM, increasing age, pre-transplant infection and diabetes, and poor access to care were associated with higher mortality whereas haploidentical donor type was associated with improved survival. For RRM, a KPS score <80, high/very high disease risk index and the presence of comorbidities were risk factors for higher mortality. Poor access to care, in addition to individual comorbidities, performance status and high-risk disease characteristics, is associated with adverse outcomes following transplant. We propose the incorporation of socioeconomic variables with patient, disease, and transplant-related variables to predict 1-year NRM.

5.
Cancer ; 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33465248

RESUMO

BACKGROUND: Individuals diagnosed with acute lymphoblastic leukemia (ALL) between the ages of 22 and 39 years experience worse outcomes than those diagnosed when they are 21 years old or younger. Treatment at National Cancer Institute-designated Comprehensive Cancer Centers (CCC) mitigates these disparities but may be associated with higher expenditures. METHODS: Using deidentified administrative claims data (OptumLabs Data Warehouse), the cancer-related expenditures were examined among patients with ALL diagnosed between 2001 and 2014. Multivariable generalized linear model with log-link modeled average monthly health-plan-paid (HPP) expenditures and amount owed by the patient (out-of-pocket [OOP]). Cost ratios were used to calculate excess expenditures (CCC vs non-CCC). Incidence rate ratios (IRRs) compared CCC and non-CCC monthly visit rates. Models adjusted for sociodemographics, comorbidities, adverse events, and months enrolled. RESULTS: Clinical and sociodemographic characteristics were comparable between CCC (n = 160) and non-CCC (n = 139) patients. Higher monthly outpatient expenditures in CCC patients ($15,792 vs $6404; P < .001) were driven by outpatient hospital HPP expenditures. Monthly visit rates and per visit expenditures for nonchemotherapy visits (IRR = 1.6; P = .001; CCC = $8247, non-CCC = $1191) drove higher outpatient hospital expenditures among CCCs. Monthly OOP expenditures were higher at CCCs for outpatient care (P = .02). Inpatient HPP expenditures were significantly higher at CCCs ($25,918 vs $13,881; ꞵ = 0.9; P < .001) before accounting for adverse events but were no longer significant after adjusting for adverse events (ꞵ = 0.4; P = .1). Hospitalizations and length of stay were comparable. CONCLUSIONS: Young adults with ALL at CCCs have higher expenditures, likely reflecting differences in facility structure, billing practices, and comprehensive patient care. It would be reasonable to consider CCCs comparable to the oncology care model and incentivize the framework to achieve superior outcomes and long-term cost savings. LAY SUMMARY: Health care expenditures in young adults (aged 22-39 years) with acute lymphoblastic leukemia (ALL) are higher among patients at National Cancer Institute-designated Comprehensive Cancer Centers (CCC) than those at non-CCCs. The CCC/non-CCC differences are significant among outpatient expenditures, which are driven by higher rates of outpatient hospital visits and outpatient hospital expenditures per visit at CCCs. Higher expenditures and visit rates of outpatient hospital visits among CCCs may also reflect how facility structure and billing patterns influence spending or comprehensive care. Young adults at CCCs face higher inpatient HPP expenditures; these are driven by serious adverse events.

6.
Support Care Cancer ; 29(1): 263-269, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32350670

RESUMO

BACKGROUND: Wax microsphere bound oxycodone was developed as an abuse-deterrent opioid and maintains a similar pharmacokinetic profile whether administered with or without an intact capsule. We hypothesized that microsphere oxycodone could be utilized for extended release analgesia in patients undergoing radiation (RT) for head-and-neck cancer (HNC) and would not need to be discontinued due to dysphagia or gastrostomy tube dependence. METHODS AND MATERIALS: We performed a prospective trial that enrolled participants > 18 years with histologically confirmed HNC who were scheduled to receive RT. Analgesia was prescribed in accordance with the WHO pain ladder. Microsphere oxycodone was initiated when total daily opioid dose exceeded 30 mg of morphine sulfate equivalent and was titrated weekly during RT. Pain level and effect on quality of life were assessed using the Brief Pain Inventory. The primary feasibility endpoint was frequency of microsphere oxycodone discontinuation within 3 months of RT for reasons other than pain resolution. RESULTS: Twenty-six eligible patients were enrolled. Microsphere oxycodone was initiated in 16 (61.5%) patients. Six (23.1%) patients utilized a gastrostomy tube to administer microsphere oxycodone during all or part of RT. Microsphere oxycodone was discontinued in 1 (7.6%) patient due to perceived inefficacy. No patients were discontinued due to toxicity or difficulty with administration. Ratings for average pain was 3.1 (± 3.4) at enrollment, 4.0 (± 2.4) at week 6 of RT, and 1.8 (± 2.2) at 3-month follow-up. CONCLUSIONS: These results support the feasibility and safety of microsphere oxycodone for extended release analgesia among patients with HNC undergoing RT.


Assuntos
Analgésicos Opioides/uso terapêutico , Neoplasias de Cabeça e Pescoço/radioterapia , Morfina/uso terapêutico , Oxicodona/uso terapêutico , Manejo da Dor/métodos , Dor/tratamento farmacológico , Analgesia , Transtornos de Deglutição , Preparações de Ação Retardada/uso terapêutico , Feminino , Gastrostomia , Humanos , Masculino , Microesferas , Pessoa de Meia-Idade , Mucosite/prevenção & controle , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Oxicodona/administração & dosagem , Estudos Prospectivos , Qualidade de Vida/psicologia
7.
Clin Cancer Res ; 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33272980

RESUMO

PURPOSE: Low-dose tamoxifen reduces breast cancer risk, but remains untested in chest-irradiated cancer survivors - a population with breast cancer risk comparable to BRCA mutation carriers. We hypothesized that low-dose tamoxifen would be safe and efficacious in reducing radiation-related breast cancer risk. EXPERIMENTAL DESIGN: We conducted an investigator-initiated, randomized, phase IIb, double-blinded, placebo-controlled trial (FDA IND107367) between 2010 and 2016 at 15 US sites. Eligibility included ≥12Gy of chest radiation by age 40y and age at enrollment ≥25y. Patients were randomized 1:1 to low-dose tamoxifen (5mg/day) or identical placebo tablets for 2y. The primary endpoint was mammographic dense area at baseline, 1y and 2y. Insulin growth factor-1 (IGF-1) plays a role in breast carcinogenesis; circulating IGF-1 and IGF-BP3 levels at baseline, 1y and 2y served as secondary endpoints. RESULTS: Seventy-two participants (low-dose tamoxifen: n=34, placebo: n=38) enrolled at a median age of 43.8y (35-49) were evaluable. They had received chest radiation at a median dose of 30.3 Gy. Compared with the placebo arm, the low-dose tamoxifen arm participants had significantly lower mammographic dense area (P=0.02) and IGF1 levels (P<0.0001), and higher IGFBP-3 levels (P=0.02). There was no difference in toxicity biomarkers (serum bone-specific alkaline phosphatase, lipids, and anti-thrombin III; urine N-telopeptide crosslinks) between the treatment arms. We did not identify any grade 3-4 adverse events related to low-dose tamoxifen. CONCLUSIONS: In this randomized trial in chest-irradiated cancer survivors, we find that low-dose tamoxifen is effective in reducing established biomarkers of breast cancer risk and could serve as a risk-reduction strategy.

8.
J Bone Miner Res ; 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33338273

RESUMO

Childhood cancer survivors treated with radiation therapy (RT) and osteotoxic chemotherapies are at increased risk for fractures. However, understanding of how genetic and clinical susceptibility factors jointly contribute to fracture risk among survivors is limited. To address this gap, we conducted genome-wide association studies of fracture risk after cancer diagnosis in 2453 participants of European ancestry from the Childhood Cancer Survivor Study (CCSS) with 930 incident fractures using Cox regression models (ie, time-to-event analysis) and prioritized sex- and treatment-stratified genetic associations. We performed replication analyses in 1417 survivors of European ancestry with 652 incident fractures from the St. Jude Lifetime Cohort Study (SJLIFE). In discovery, we identified a genome-wide significant (p < 5 × 10-8 ) fracture risk locus, 16p13.3 (HAGHL), among female CCSS survivors (n = 1289) with strong evidence of sex-specific effects (psex-heterogeneity < 7 × 10-6 ). Combining discovery and replication data, rs1406815 showed the strongest association (hazard ratio [HR] = 1.43, p = 8.2 × 10-9 ; n = 1935 women) at this locus. In treatment-stratified analyses in the discovery cohort, the association between rs1406815 and fracture risk among female survivors with no RT exposures was weak (HR = 1.22, 95% confidence interval [CI] 0.95-1.57, p = 0.11) but increased substantially among those with greater head/neck RT doses (any RT: HR = 1.88, 95% CI 1.54-2.28, p = 2.4 × 10-10 ; >36 Gray only: HR = 3.79, 95% CI 1.95-7.34, p = 8.2 × 10-5 ). These head/neck RT-specific HAGHL single-nucleotide polymorphism (SNP) effects were replicated in female SJLIFE survivors. In silico bioinformatics analyses suggest these fracture risk alleles regulate HAGHL gene expression and related bone resorption pathways. Genetic risk profiles integrating this locus may help identify female survivors who would benefit from targeted interventions to reduce fracture risk. © 2020 American Society for Bone and Mineral Research (ASBMR).

9.
Cancer ; 2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33369894

RESUMO

BACKGROUND: Sarcopenia is associated with adverse outcomes among older adults with cancer; however, no easily applied sarcopenia measure exists for use in clinical practice. The use of SARC-F, a 5-item self-reported sarcopenia screening questionnaire, among older adults with cancer remains to be investigated. METHODS: Older adults (aged ≥60 years) with cancer enrolled in the University of Alabama Cancer and Aging Resilience Evaluation Registry were identified. Patients completed the SARC-F questionnaire (with scores ≥4 considered positive for sarcopenia). The authors assessed for differences in geriatric assessment domain impairments, health-related quality of life, and health care utilization between those with and without sarcopenia using multivariate regression, then assessed the association of sarcopenia with survival using Kaplan-Meier methods and a Cox regression model, adjusting for covariates. RESULTS: In total, 256 older adults were identified. The median age was 69 years, 59% of participants were men, and 75% were White. The median SARC-F score was 2 (interquartile range, 0-4), and 33% of participants screened positive. Those with sarcopenia had higher odds of having multiple impairments, including impaired instrumental activities of daily living (adjusted odds ratio [aOR], 18.1; 95% CI, 7.5-43.8) and frailty (aOR, 43.5; 95% CI, 17.7-106.8) as well as reduced physical and mental health-related quality of life (ß coefficient, -13.6 and -11.5, respectively) and increased emergency room visits (aOR, 2.4; 95% CI, 1.3-4.7). Furthermore, sarcopenia was independently associated with inferior overall survival (adjusted hazard ratio, 2.98; 95% CI, 1.1-8.3; P = .04). CONCLUSIONS: One-third of older adults with cancer in this cohort screened positive for sarcopenia using the SARC-F screening questionnaire, and these positive scores are associated with geriatric assessment domain impairments, reduced health-related quality of life, increased emergency room visits, and inferior overall survival.

10.
Ann Surg ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33201090

RESUMO

OBJECTIVE: The aim of this study was to obtain feedback from key stakeholders and end users to identify program strengths and weaknesses to plan for wider dissemination and implementation of the Virtual Acute Care for Elders (Virtual ACE) program, a novel intervention that improves outcomes for older surgical patients. BACKGROUND: Virtual ACE was developed to deliver evidence-based geriatric care without requiring daily presence of a geriatrician. Previous work demonstrated that Virtual ACE increased mobility and decreased delirium rates for surgical patients. METHODS: We conducted semi-structured interviews with 30 key stakeholders (physicians, nurses, hospital leadership, nurse managers, information technology staff, and physical/occupational therapists) involved in the implementation and use of the program. RESULTS: Our stakeholders indicated that Virtual ACE was extremely empowering for bedside nurses. The program helped nurses identify older patients who were at risk for a difficult postoperative recovery. Virtual ACE also gave them skills to manage complex older patients and more effectively communicate their needs to surgeons and other providers. Nurse managers felt that Virtual ACE helped them allocate limited resources and plan their unit staffing assignments to better manage the needs of older patients. The main criticism was that the Virtual ACE Tracker that displayed patient status was difficult to interpret and could be improved by a better design interface. Stakeholders also felt that program training needed to be improved to accommodate staff turnover. CONCLUSIONS: Although respondents identified areas for improvement, our stakeholders felt that Virtual ACE empowered them and provided effective tools to improve outcomes for older surgical patients.

11.
J Cancer Surviv ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33170480

RESUMO

PURPOSE: Cancer survivors are at risk for late effects from therapeutic exposures, including cardiovascular complications. To improve outcomes among adolescents and young adults (AYA) with cancer, the National Comprehensive Cancer Network (NCCN) released guidelines for screening services (based on the Children's Oncology Group Long-Term Follow-Up [LTFU] guidelines) for survivors of AYA cancer. To better understand survivorship care gaps, we conducted a baseline evaluation of cardiomyopathy screening among survivors of AYA cancers. METHODS: Members of Kaiser Permanente Southern California diagnosed with cancer between ages 15 and 39 from 2000 to 2010 with at least 5-year survival after diagnosis who were exposed to chest radiation and/or anthracyclines were included. We calculated the Prevention Index ([PI], proportion of person-time covered by receipt of preventive services relative to the total person-time eligible) to evaluate adherence to recommended cardiomyopathy screenings based on the LTFU through 2016. Predictors for screening were evaluated in multivariable logistic regression. RESULTS: Among 479 survivors recommended for cardiomyopathy screening, 28 received at least one screening, and the mean PI was 2.38% (SD = 13.05%, median = 0.00%). Compared to stage I, survivors of stage II (odds ratio [OR] = 5.56 [1.05-29.46]) and stage III/IV cancer (OR = 6.08 [1.10-33.54]) were more likely to receive cardiomyopathy screening. CONCLUSIONS: Cardiomyopathy screening among survivors was low around the time when NCCN AYA oncology guidelines were released. IMPLICATIONS FOR CANCER SURVIVORS: Our study highlights significant room for improvement for adherence to cardiomyopathy screening recommendations among survivors of AYA cancer. Attention is needed to ensure that recommended cardiomyopathy screenings are met for better management of cardiomyopathy late effects.

12.
Cancer ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33206383

RESUMO

BACKGROUND: Blood or bone marrow transplantation (BMT) survivors with frailty are at a higher risk of subsequent mortality. Longitudinal trends in the frailty state are not known and could help identify vulnerable subpopulations at risk of subsequent adverse events. METHODS: This study included a cohort of 470 autologous and allogeneic BMT recipients who had survived ≥2 years after BMT and completed a baseline questionnaire (t1) at a median of 7.3 years after BMT and a follow-up questionnaire (t2) 13.2 years after t1. The main outcome was change in frailty state between t1 and t2. Frailty phenotype was defined as exhibiting ≥3 of the following characteristics: clinically underweight, exhaustion, low energy expenditure, slow walking speed, and muscle weakness. The following categories of change in frailty state were evaluated: worsened, improved, and stable. RESULTS: Of the 470 participants, 36.4% were aged ≥60 years at t1, and 50.6% were men. The prevalence of frailty increased from 4.8% at t1 to 9.6% at t2. Worsening was observed in 18.8% of patients, and improvement was reported in 9.7%. Pre-BMT exposure to vincristine (odds ratio [OR], 2.1; 95% CI, 1.3-3.39) was associated with worsening. Female sex (OR, 1.5; 95% CI, 0.93-2.4) was associated with a trend toward worsening. Pre-BMT exposure to vincristine (OR, 2.79; 95% CI, 1.44-5.43), a history of chronic graft-versus-host disease (OR, 2.58; 95% CI, 1.2-5.5), and grade 3 and 4 chronic health conditions at t1 (OR, 2.1; 95% CI, 1.08-4.33) were associated with frailty at t2. CONCLUSIONS: In a cohort of BMT survivors who were followed longitudinally for a median of 20.6 years from BMT, the frailty status worsened for approximately20% over a 13-year timespan. BMT survivors who are at risk for worsening frailty could benefit from targeted interventions.

13.
Pediatr Clin North Am ; 67(6): 1135-1154, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33131538

RESUMO

The authors' objective is to provide a brief update on recent advances in knowledge relating to subsequent primary neoplasms developing in survivors of childhood cancer. This includes a summary of established large-scale cohorts, risks reported, and contrasts with results from recently established large-scale cohorts of survivors of adolescent and young adult cancer. Recent evidence is summarized concerning the role of radiotherapy and chemotherapy for childhood cancer and survivor genomics in determining the risk of subsequent primary neoplasms. Progress with surveillance, screening, and clinical follow-up guidelines is addressed. Finally, priorities for future research are outlined.

14.
J Geriatr Oncol ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33160953

RESUMO

BACKGROUND: Depression among older adults with cancer is under recognized and under treated. This study characterizes the burden of depression in older adults with gastrointestinal (GI) malignancies prior to chemotherapy and its relationship with geriatric assessment (GA) domains, health-related quality of life (HRQOL), and self-reported healthcare utilization. METHODS: Patients ≥60 years in GI oncology clinics at UAB were asked to complete a GA entitled the Cancer & Aging Resilience Evaluation (CARE). We examined depression using the Patient-Reported Outcomes Measurement Information System (PROMIS®) Depression four-item short form; moderate/severe depression was defined by a t-score ≥ 60. Multivariate analysis was used to examine associations between those with and without moderate/severe depression. RESULTS: Of 355 included patients, 46 had mild depression (13%) and an additional 46 patients had moderate/severe depression (13%). After adjustment for age, sex, education, cancer type, and cancer stage, those who reported moderate/severe depression had a significantly increased odds of reporting falls (adjusted odds ratio [aOR] 4.01, 95% confidence interval [CI] 1.94-8.26), dependence in IADLs (aOR 7.06,CI 2.91-17.1), dependence in ADLs (aOR 6.23, CI 2.89-13.4), malnutrition (aOR 5.86, CI 2.40-14.3), frailty (aOR 13.7, CI 5.80-32.1), and fatigue (aOR 11.2, CI 3.31-37.6). Moderate/severe depression was also significantly associated with worse physical (aOR 7.58, CI 3.30-17.4) and mental (aOR 26.3, CI 10.1-68.8) HRQOL sub-scores, without significant differences in healthcare utilization. CONCLUSIONS: More than one out of eight older adults with a GI malignancy reported moderate/severe depression prior to chemotherapy, which was associated with impairments in several GA domains and HRQOL.

15.
Cancer ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33048379

RESUMO

BACKGROUND: Treatment characteristics such as cranial radiation therapy (CRT) do not fully explain adiposity risk in childhood acute lymphoblastic leukemia (ALL) survivors. This study was aimed at characterizing genetic variation related to adult body mass index (BMI) among survivors of childhood ALL. METHODS: Genetic associations of BMI among 1458 adult survivors of childhood ALL (median time from diagnosis, 20 years) were analyzed by multiple approaches. A 2-stage genome-wide association study in the Childhood Cancer Survivor Study (CCSS) and the St. Jude Lifetime Cohort Study (SJLIFE) was performed. BMI was a highly polygenic trait in the general population. Within the known loci, the BMI percent variance explained was estimated, and additive interactions (chi-square test) with CRT in the CCSS were evaluated. The role of DNA methylation in CRT interaction was further evaluated in a subsample of ALL survivors. RESULTS: In a meta-analysis of the CCSS and SJLIFE, 2 novel loci associated with adult BMI among survivors of childhood ALL (LINC00856 rs575792008 and EMR1 rs62123082; PMeta < 5E-8) were identified. It was estimated that the more than 700 known loci explained 6.2% of the variation in adult BMI in childhood ALL survivors. Within the known loci, significant main effects for 23 loci and statistical interactions with CRT at 9 loci (P < 7.0E-5) were further identified. At 2 CRT-interacting loci, DNA methylation patterns may have differed by age. CONCLUSIONS: Adult survivors of childhood ALL have genetic heritability for BMI similar to that observed in the general population. This study provides evidence that treatment with CRT can modify the effect of genetic variants on adult BMI in childhood ALL survivors.

16.
J Clin Oncol ; 38(35): 4194-4207, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33078972

RESUMO

PURPOSE: As new evidence is available, the International Late Effects of Childhood Cancer Guideline Harmonization Group has updated breast cancer surveillance recommendations for female survivors of childhood, adolescent, and young adult cancer. METHODS: We used evidence-based methods to apply new knowledge in refining the international harmonized recommendations developed in 2013. The guideline panel updated the systematic literature review, developed evidence summaries, appraised the evidence, and updated recommendations on the basis of evidence, clinical judgement, and consideration of benefits versus the harms of the surveillance interventions while attaining flexibility in implementation across different health care systems. The GRADE Evidence-to-Decision framework was used to translate evidence to recommendations. A survivor information form was developed to counsel survivors about the potential harms and benefits of surveillance. RESULTS: The literature update identified new study findings related to the effects of prescribed moderate-dose chest radiation (10 to 19 Gy), radiation dose-volume, anthracyclines and alkylating agents in non-chest irradiated survivors, and the effects of ovarian function on breast cancer risk. Moreover, new data from prospective investigations were available regarding the performance metrics of mammography and magnetic resonance imaging among survivors of Hodgkin lymphoma. Modified recommendations include the performance of mammography and breast magnetic resonance imaging for survivors treated with 10 Gy or greater chest radiation (strong recommendation) and upper abdominal radiation exposing breast tissue at a young age (moderate recommendation) at least annually up to age 60 years. As a result of inconsistent evidence, no recommendation could be formulated for routine breast cancer surveillance for survivors treated with any type of anthracyclines in the absence of chest radiation. CONCLUSION: The newly identified evidence prompted significant change to the recommendations formulated in 2013 related to moderate-dose chest radiation and anthracycline exposure as well as breast cancer surveillance modality.

17.
Clin Pharmacol Ther ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33124053

RESUMO

6-mercaptopurine (6-MP) is widely used in the treatment of acute lymphoblastic leukemia (ALL), and its cytotoxicity is primarily mediated by thioguanine nucleotide (TGN) metabolites. A recent genomewide association study has identified germline polymorphisms (e.g., rs72846714) in the NT5C2 gene associated with 6-MP metabolism in patients with ALL. However, the full spectrum of genetic variation in NT5C2 is unclear and its impact on 6-MP drug activation has not been comprehensively examined. To this end, we performed targeted sequencing of NT5C2 in 588 children with ALL and identified 121 single nucleotide polymorphisms nominally associated with erythrocyte TGN during 6-MP treatment (P < 0.05). Of these, 61 variants were validated in a replication cohort of 372 children with ALL. After considering linkage disequilibrium and multivariate analysis, we confirmed two clusters of variants, represented by rs72846714 and rs58700372, that independently affected 6-MP metabolism. Functional studies showed that rs58700372 directly altered the activity of an intronic enhancer, with the variant allele linked to higher transcription activity and reduced 6-MP metabolism (lower TGN). By contrast, rs72846714 was not located in a regulatory element and instead its association signal was explained by linkage disequilibrium with a proximal functional variant rs12256506 that activated NT5C2 transcription in-cis. Our results indicated that NT5C2 germline variation significantly contributes to interpatient variability in thiopurine drug disposition.

18.
JCO Oncol Pract ; : OP2000601, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33125296

RESUMO

PURPOSE: Financial distress (FD) among older adults with cancer is not well studied. We sought to characterize prevalence and factors associated with FD among older adults with cancer and the association of FD with geriatric assessment (GA) -identified deficits. PATIENTS AND METHODS: We included adults age ≥ 60 years with cancer in the University of Alabama at Birmingham Cancer and Aging Resilience Evaluation Registry who underwent GA during initial consultation with a medical oncologist before starting systemic therapy. We captured FD using a single-item question: "Do you have to pay for more medical care than you can afford?" We built multivariable models to study the impact of sociodemographic/clinical factors on FD as well as the association of FD with GA impairments. RESULTS: We identified 447 older adults with a median age of 69 years; 60% were men, 75% were White, and colorectal (26%) and pancreatic (19%) cancers were the most common. Overall, 27% (n = 121) reported having FD. Factors associated with FD included being Black (v White; odds ratio [OR], 2.26; 95% CI, 1.35 to 3.81; P = .002), being disabled/unemployed (v employed; OR, 2.60; 95% CI, 1.17 to 5.76; P = .019), and having an advanced degree (v less than high school; OR, 0.13; 95% CI, 0.03 to 0.65; P = .012). Patients with FD were more likely to report several GA impairments, including depression (OR, 2.10; 95% CI, 1.06 to 4.18; P = .034) and impaired health-related quality of life in physical (ß = -2.82; P = .014) and mental health domains (ß = -3.31; P = .002). CONCLUSION: More than a quarter of older adults with cancer reported FD at the time of initial presentation to an oncologist. Several demographic factors and GA impairments were associated with FD.

19.
Cancer ; 126(23): 5147-5155, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32885848

RESUMO

BACKGROUND: A majority of older adults with cancer develop malnutrition; however, the implications of malnutrition among this vulnerable population are poorly understood. The goal of this study was to quantify the prevalence of nutrition related-symptoms and malnutrition among older adults with gastrointestinal (GI) malignancies and the association of malnutrition with geriatric assessment (GA) impairment, health-related quality of life (HRQoL), and health care utilization. METHODS: We performed a cross-sectional study of older adults (≥60 years) who were referred to the GI Oncology clinic at the University of Alabama at Birmingham. Participants underwent the Cancer & Aging Resilience Evaluation survey that includes the abbreviated Patient-Generated Subjective Global Assessment of nutrition. Nutrition scores were dichotomized into normal (0-5) and malnourished (≥6), and multivariate analyses adjusted for demographics, cancer type, and cancer stage were used to examine associations with GA impairment, HRQoL, and health care utilization. RESULTS: A total of 336 participants were included (men, 56.8%; women, 43.2%), with a mean age of 70 years (standard deviation, ±7.2 years) and colorectal cancer (33.6%) and pancreatic cancer (24.4%) being the most common diagnoses. Overall, 52.1% of participants were identified as malnourished. Malnutrition was associated with a higher prevalence of several GA impairments, including 1 or more falls (adjusted odds ratio [aOR], 2.1), instrumental activities of daily living impairment (aOR, 4.1), and frailty (aOR, 8.2). Malnutrition was also associated with impaired HRQoL domains; both physical (aOR, 8.7) and mental (aOR, 5.0), and prior hospitalizations (aOR, 2.2). CONCLUSION: We found a high prevalence of malnutrition among older adults with GI malignancies that was associated with increased GA impairments, reduced HRQoL, and increased health care utilization.

20.
PLoS One ; 15(9): e0237792, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881892

RESUMO

BACKGROUND: Ewing sarcoma (EwS) is a rare, aggressive solid tumor of childhood, adolescence and young adulthood associated with pathognomonic EWSR1-ETS fusion oncoproteins altering transcriptional regulation. Genome-wide association studies (GWAS) have identified 6 common germline susceptibility loci but have not investigated low-frequency inherited variants with minor allele frequencies below 5% due to limited genotyped cases of this rare tumor. METHODS: We investigated the contribution of rare and low-frequency variation to EwS susceptibility in the largest EwS genome-wide association study to date (733 EwS cases and 1,346 unaffected controls of European ancestry). RESULTS: We identified two low-frequency variants, rs112837127 and rs2296730, on chromosome 20 that were associated with EwS risk (OR = 0.186 and 2.038, respectively; P-value < 5×10-8) and located near previously reported common susceptibility loci. After adjusting for the most associated common variant at the locus, only rs112837127 remained a statistically significant independent signal (OR = 0.200, P-value = 5.84×10-8). CONCLUSIONS: These findings suggest rare variation residing on common haplotypes are important contributors to EwS risk. IMPACT: Motivate future targeted sequencing studies for a comprehensive evaluation of low-frequency and rare variation around common EwS susceptibility loci.


Assuntos
Loci Gênicos , Predisposição Genética para Doença , Variação Genética , Células Germinativas/metabolismo , Sarcoma de Ewing/genética , Estudo de Associação Genômica Ampla , Humanos , Desequilíbrio de Ligação/genética , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética
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