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Inflammatory Biomarkers, Hematopoietic Stem Cells, and Symptoms in Breast Cancer Patients Undergoing Adjuvant Radiation Therapy.

ABSTRACT: Background:Fatigue and insomnia are common symptoms experienced by breast cancer patients undergoing adjuvant radiation therapy (RT), yet the underlying mechanisms of these symptoms are unclear. In particular, the roles of hematopoietic stem cells (HSCs) and inflammatory cytokines remain to be elucidated. Methods:Breast cancer patients (n?=?147) completed questionnaires to longitudinally assess symptoms before, during, and after adjuvant RT. Phlebotomies were performed prior to RT, at the second and fifth treatment fractions, end of treatment (EOT), and 1 month after completing RT, assessing for CD34+, CD45+, full hematology, and 17 inflammatory cytokines. The associations between symptoms and all biomarkers were evaluated. All statistical tests were 2-sided. Results:General fatigue and insomnia worsened with RT, with peak levels observed at EOT, which remained statistically significant even after controlling for anxiety and depression (P?

SUBMITTER: Shi W

PROVIDER: S-EPMC7583146 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Inflammatory Biomarkers, Hematopoietic Stem Cells, and Symptoms in Breast Cancer Patients Undergoing Adjuvant Radiation Therapy.

Shi Wei W Misra Shagun S Li Madeline M Su Jie J Chong Lisa P LP McCuske Megan M Williams Justin J Xu Wei W Ghoraie Laleh S LS Sutherland D Robert DR Han Kathy K Minden Mark D MD Bratman Scott V SV Yip Kenneth W KW Liu Fei-Fei FF

JNCI cancer spectrum 20200508 5

<h4>Background</h4>Fatigue and insomnia are common symptoms experienced by breast cancer patients undergoing adjuvant radiation therapy (RT), yet the underlying mechanisms of these symptoms are unclear. In particular, the roles of hematopoietic stem cells (HSCs) and inflammatory cytokines remain to be elucidated.<h4>Methods</h4>Breast cancer patients (n = 147) completed questionnaires to longitudinally assess symptoms before, during, and after adjuvant RT. Phlebotomies were performed prior to RT ...[more]

PMID: 33134822

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Project description:Purpose:Adjuvant radiation therapy has historically been underused by black patients with breast cancer compared with white patients. We prospectively investigated factors, including sociocultural, psychosocial, and health care factors, that may be associated with the use or omission of adjuvant radiation therapy by both racial groups. Methods and Materials:Women with primary invasive, nonmetastatic breast cancer were recruited from hospitals and through community outreach efforts in the Washington, DC, and Detroit, Michigan, areas between July 2006 and April 2011. Data were collected via telephone interviews regarding psychosocial (eg, self-efficacy) and health care factors (eg, communication) at the time they received a diagnosis. Clinical data were extracted from their medical charts after the completion of treatment. We examined the association among multiple demographic, socio-cultural, healthcare process factors and the use of radiotherapy. Logistic multivariable regression models identified associations with radiotherapy receipt. Results:Among 395 eligible and consenting women, 315 had complete baseline data, and 217 were in the final analytical sample, having met criteria for adjuvant breast or chest wall radiation therapy after breast conservation surgery or mastectomy. Among women eligible for radiation, all were insured, 59% were black, the mean age was 55.4 years, and the majority had stage I or II disease. Overall, approximately 70% percent of women received adjuvant radiation therapy. On multivariable analyses, the likelihood of receiving adjuvant radiation therapy was higher for those who were black with any level of indication for radiation therapy (odds ratio 2.21; P < .01), those for whom comorbidities were present, and those who demonstrated positive sociocultural factors such as self-efficacy and high reported rates of provider communication about radiation therapy (odds ratio 1.20; P < .05). Among women with strong indications for radiation therapy, there was no significant association with race on multivariable analysis. Conclusions:Our findings suggest that among women with any indication for radiation therapy, black patients were more likely to receive radiation therapy compared with white patients. Furthermore, data suggest improved provider communication and self-efficacy are important predictors of receipt of radiation therapy. Further studies exploring the effects of provider communication and sociocultural factors to diverse patient populations may be warranted.

Project description:Autologous hematopoietic stem cell transplantation (aHSCT) is a highly efficient treatment of multiple sclerosis (MS), and hence it likely normalizes pathological and/or enhances beneficial processes in MS. The disease pathomechanisms include neuroinflammation, glial cell activation and neuronal damage. We studied biomarkers that in part reflect these, like markers for neuroinflammation (C-X-C motif chemokine ligand (CXCL) 9, CXCL10, CXCL13, and chitinase 3-like 1 (CHI3L1)), glial perturbations (glial fibrillary acidic protein (GFAP) and in part CHI3L1), and neurodegeneration (neurofilament light chain (NfL)) by enzyme-linked immunosorbent assays (ELISA) and single-molecule array assay (SIMOA) in the serum and cerebrospinal fluid (CSF) of 32 MS patients that underwent aHSCT. We sampled before and at 1, 3, 6, 12, 24 and 36 months after aHSCT for serum, as well as before and 24 months after aHSCT for CSF. We found a strong increase of serum CXCL10, NfL and GFAP one month after the transplantation, which normalized one and two years post-aHSCT. CXCL10 was particularly increased in patients that experienced reactivation of cytomegalovirus (CMV) infection, but not those with Epstein-Barr virus (EBV) reactivation. Furthermore, patients with CMV reactivation showed increased Th1 phenotype in effector memory CD4+ T cells. Changes of the other serum markers were more subtle with a trend for an increase in serum CXCL9 early post-aHSCT. In CSF, GFAP levels were increased 24 months after aHSCT, which may indicate sustained astroglia activation 24 months post-aHSCT. Other CSF markers remained largely stable. We conclude that MS-related biomarkers indicate neurotoxicity early after aHSCT that normalizes after one year while astrocyte activation appears increased beyond that, and increased serum CXCL10 likely does not reflect inflammation within the central nervous system (CNS) but rather occurs in the context of CMV reactivation or other infections post-aHSCT.

Dataset Information

Inflammatory Biomarkers, Hematopoietic Stem Cells, and Symptoms in Breast Cancer Patients Undergoing Adjuvant Radiation Therapy.

Publications

Inflammatory Biomarkers, Hematopoietic Stem Cells, and Symptoms in Breast Cancer Patients Undergoing Adjuvant Radiation Therapy.

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