Publications by authors named "Andrew Livingston"
Purpose: FHD-609, a potent, selective, heterobifunctional degrader of bromodomain-containing protein 9 (BRD9), was evaluated for treatment of patients with advanced synovial sarcoma (SS) or SMARCB1-deficient tumors.
Patients And Methods: In this multinational, open-label, phase 1 study (NCT04965753), patients received FHD609 intravenously at escalating doses either twice weekly (BIW) (5 to 80 mg; n=40) or once weekly (QW) (40 to 120 mg; n=15).
Results: Fifty-five patients received FHD-609 for a median of 43 days.
Article Synopsis
- Malignant peripheral nerve sheath tumors (MPNSTs) show altered DNA methylation patterns, suggesting these changes could be used as specific biomarkers for NF1 patient screening.
- Researchers conducted a study involving DNA methylation profiling from tumor and adjacent tissue samples of 13 MPNST patients, finding 73 candidate CpGs that could distinguish MPNSTs from neurofibromas.
- Five validated biomarkers demonstrated high sensitivity and specificity in tissue detection, and higher methylation levels were observed in plasma tests, indicating potential for early detection of MPNST in NF1 patients.
PEGylation (the covalent attachment of one or more poly(ethylene glycol) (PEG) units to a therapeutic) is a well-established technique in the pharmaceutical industry to increase blood-residence time and decrease immunogenicity. A challenging aspect of PEGylation is the dispersity of PEGylation agents, which results in batch-to-batch variations and analytical limitations. Herein, we present an approach to overcome these limitations by manufacturing a defined molecular weight (dispersity-free) PEGylation agent.
View Article and Find Full Text PDFBackground: The Patient Protection and Affordable Care Act (ACA) allowed Americans aged 19-25 years to remain on their parents' health insurance plans until age 26 years (the Dependent Care Expansion [DCE]). Have those with cancer diagnoses benefited?
Methods: The ACE DCE 7-year age range of 19-25 years was compared for changes in cancer survival and mortality before and after enactment of the ACA with groups that were younger and older (in 7-year age spans: ages 12-18 and 26-32 years, respectively). Cancer death data for the entire United States were obtained from the Centers for Disease Control and Prevention, and relative survival data of patients who were diagnosed with cancer were obtained from the National Cancer Institute Surveillance, Epidemiology, and End Results regions representing 42%-44% of the country.
Rhabdomyosarcomas are the most common soft tissue sarcoma in children, and pediatric alveolar rhabdomyosarcoma (ARMS) prognosis has improved based on cooperative studies. However, in adults, ARMS is significantly rarer, has poorer outcomes, and currently lacks optimal treatment strategies. This study aimed to evaluate the clinical outcome of an adult ARMS population with different front-line systemic chemotherapies and determine if any chemotherapy regimen is associated with improved survival.
View Article and Find Full Text PDFBackground: Neighborhood socioeconomic deprivation has been linked to adverse health outcomes, yet it is unclear whether neighborhood-level social determinants of health (SDOH) measures affect overall survival in adolescent and young adult patients with cancer.
Methods: This study used a diverse cohort of adolescent and young adult patients with cancer (N = 10 261) seen at MD Anderson Cancer Center. Zip codes were linked to Area Deprivation Index (ADI) values, a validated neighborhood-level SDOH measure, with higher ADI values representing worse SDOH.
Article Synopsis
- The study examines health-related quality of life (HRQoL) in adolescents and young adults (AYAs) diagnosed with cancer, finding that this aspect has not been deeply explored previously.
- It analyzed data from 3,497 cancer survivors using the Short-Form 12 Health Survey and discovered that HRQoL scores varied significantly based on factors like age, sex, and race/ethnicity.
- Notably, poor physical and mental HRQoL scores at the time of diagnosis were linked to a higher risk of reduced overall survival in these survivors.
Article Synopsis
- There is a genetic link to heart problems caused by anthracycline treatment in childhood cancer survivors, but it's unclear if this also applies to adolescent and young adult (AYA) cancer patients.
- A study analyzed 45 genetic variants in 253 AYA patients who received anthracyclines and found four variants associated with heart dysfunction, with some variants showing opposite effects compared to childhood survivors.
- Further testing on stem cell-derived heart cells revealed significant changes in gene expression for two of the variants, indicating that genetics indeed play a role in cardiac issues for AYA cancer survivors, but the impact may differ from that seen in children.
Purpose: Soft tissue sarcomas (STSs) of the head and neck (H&N) are rare malignancies that are challenging to manage. We sought to describe the outcomes of patients treated with curative intent using combined surgery and radiation therapy (RT) for H&N STS.
Methods And Materials: We performed a single-institution retrospective review of patients with nonmetastatic STS of the H&N who were treated from 1968 to 2020.
Background: Undifferentiated pleomorphic sarcomas (UPSs) are amongst the most common subtypes of soft-tissue sarcomas. Few real-world data on the use of immune checkpoint blockade (ICB) in UPS patients and other high-grade pleomorphic STS patients are available.
Purpose: The purpose of our study is to describe the efficacy and toxicity of ICB in patients with advanced UPSs and other high-grade pleomorphic sarcomas treated at our institution.
Article Synopsis
- - The study focuses on young adult cancer survivors, examining how stress (related to cancer and daily life) affects their health behaviors and quality of life (QoL) as they transition into survivorship, along with the role of their partners in this process.
- - Young adults often struggle with health behaviors post-treatment, and understanding the immediate and long-term effects of stress can help improve their overall health outcomes.
- - The research will involve 150 participants who will complete daily online surveys over two years to track stress, health behaviors, and QoL, aiming to identify patterns and relationships between these factors for both survivors and their partners.
Article Synopsis
- Targeting the DNA damage response (DDR) pathway could be a promising treatment strategy for leiomyosarcoma (LMS), with RNase H2 loss identified as a key alteration for potential therapies.
- A study found that RNase H2 loss is significantly more prevalent in LMS (11.5%) compared to other tumors (3.8%), particularly in uterine LMS (21%) and soft-tissue LMS (30%).
- Although RNase H2 loss and homozygous deletions of RNASEH2B exist in LMS, they did not correlate with significant differences in overall survival among U-LMS patients, but the accuracy of RNase H2 testing suggests its potential use in future clinical trials targeting DDR.
A randomized, non-comparative phase 2 study of neoadjuvant immune-checkpoint blockade in retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma.
Nat Cancer
April 2024
Article Synopsis
- A randomized phase 2 trial was conducted to evaluate the effectiveness of neoadjuvant immune checkpoint blockade (ICB) therapies (nivolumab and nivolumab/ipilimumab) in patients with resectable retroperitoneal DDLPS and extremity/truncal UPS.
- The primary endpoint of pathologic response showed a median hyalinization of 8.8% in DDLPS and 89% in UPS, with secondary endpoints focusing on immune changes and survival rates over time.
- Results indicated that lower pre-treatment regulatory T cell densities correlated with better pathological outcomes, and that neoadjuvant ICB led to significant immune changes and benefits, particularly in patients with UPS when combined with radiation therapy
Background: In the general population, individuals with minoritized sexual orientation and gender identity have a higher burden of chronic health conditions than heterosexual individuals. However, the extent to which sexual orientation is associated with excess burden of chronic conditions in adolescent and young adult cancer survivors (AYACS) is unknown.
Methods: Lesbian, gay, and bisexual (LGB) AYACSs, LGB individuals without a history of cancer, and heterosexual AYACSs were identified by self-reported data from the cross-sectional National Health Interview Survey (2013-2020).
Purpose: Survivors of adolescent and young adult (AYA) cancer experience psychological distress and insufficient access to mental health care. Few studies have investigated racial/ethnic disparities in psychological health outcomes in this population. This study compared psychological distress, mental health care use, and inability to afford mental health care between Hispanic/Latino survivors of AYA cancer and Hispanic/Latino controls.
View Article and Find Full Text PDFPurpose: The lungs are the most common site of metastasis for patients with soft tissue sarcoma. SABR is commonly employed to treat lung metastases among select patients with sarcoma with limited disease burden. We sought to evaluate outcomes and patterns of failure among patients with sarcoma treated with SABR for their lung metastases.
View Article and Find Full Text PDFBackground: Early skeletal muscle loss has been observed in adolescent and young adult (AYA) sarcoma patients undergoing treatment. Identification of individuals within the AYA populace that are at greatest risk of anthracycline-induced skeletal muscle loss is unknown. Moreover, investigations which seek out underlying causes of skeletal muscle degradation during chemotherapy are critical for understanding, preventing, and reducing chronic health conditions associated with poor skeletal muscle status.
View Article and Find Full Text PDFPurpose: Chondrosarcomas are the most common primary bone tumor in adults. Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations are prevalent. We aimed to assess the clinico-genomic properties of IDH mutant versus IDH wild-type (WT) chondrosarcomas as well as alterations in other genes.
View Article and Find Full Text PDFArticle Synopsis
- The study aims to identify biomarkers that can help pinpoint patients at high risk for developing heart issues after receiving doxorubicin (DOX) treatment, focusing on better monitoring and early interventions.
- Mice were tested with DOX and assessed for changes in specific miRNAs, cytokines, and cardiac function both before and after treatment, alongside a comparable study in sarcoma patients.
- Results showed that certain miRNAs and cytokines increased in DOX-treated mice and patients, indicating potential biomarkers for predicting heart problems, while exercise seemed to prevent these changes in mice.
While there are known disparities in socioeconomic status (SES) and health outcomes among racially and ethnically minoritized adolescent and young adult (AYA; ages 15-39 years at diagnosis) cancer survivors compared with White survivors, outcomes in the Asian survivor population are understudied. To better understand the association of an AYA cancer diagnosis with SES and health outcomes within a minoritized population, the current study makes comparisons between individuals of the same race or ethnicity with and without a history of AYA cancer. Non-Hispanic, Asian AYA cancer survivors and non-Hispanic, Asian age- and sex-matched controls were identified from self-reported data in the National Health Interview Survey (2009-2020).
View Article and Find Full Text PDFPurpose: Radiation therapy (RT) may cause toxicities in adolescents and young adults (AYAs, age 15-39 years) with cancer. However, the range of RT-related toxicities in AYAs and the affect on health-related quality of life (HRQOL) has not been well studied. We performed a cross-sectional study in AYAs with cancer who received RT to identify RT-related toxicities and examine their impact on HRQOL.
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- Single-cell RNA sequencing (scRNA-seq) is a powerful tool for analyzing complex tissues and understanding individual cell types, but it can introduce biases in gene expression due to tissue processing methods.
- The study focused on sarcomas, specifically three aggressive subtypes (osteosarcoma, Ewing sarcoma, and desmoplastic small round cell tumor), and evaluated how different cell dissociation techniques affect gene expression results.
- Findings revealed significant transcriptional biases from various dissociation methods, but classic sarcoma gene signatures remained detectable, indicating that these biases can be corrected computationally.
Background: Radiation therapy (RT) is a common treatment for adolescents and young adults (AYAs, 15-39 years old) with cancer; however, it may cause toxicities that affect health-related quality-of-life (HRQOL). Thus, we assessed HRQOL in AYAs before, during, and after RT.
Methods: We identified 265 AYAs who completed HRQOL PROMIS® surveys before (n = 87), during (n = 84), or after (n = 94) RT.
Poor Sit-to-Stand Performance in Adolescent and Young Adult Patients with Sarcoma.
J Adolesc Young Adult Oncol
December 2023
Adolescents and young adult (AYA) patients with sarcoma are at heightened risk of reduced physical capacity and disease-related weakness. Sit-to-stand (STS) performance correlates with lower extremity functionality and activities of daily living; however, little is known regarding the relationship between muscular status and STS performance in patients with sarcoma. This study assessed STS performance in patients with sarcoma and the association between STS performance and the skeletal muscle index (SMI) and skeletal muscle density (SMD).
View Article and Find Full Text PDFPurpose: Developing new therapeutics for any of the more than 100 sarcoma subtypes presents a challenge. After progression from standard therapies, patients with sarcoma may be referred for enrollment in early-phase trials. This study aimed to investigate whether enrollment in biomarker-matched early-phase clinical trials leads to better outcomes for patients with advanced sarcoma.
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