Patient advocates, referring to those individuals that have been diagnosed with the disease for which they advocate, are essential stake holders in healthcare. For those facing the stages of being diagnosed with Inflammatory Breast Cancer (IBC), the \"call to advocate\" is an immediate response to being diagnosed with a rare and aggressive disease that progresses rapidly, often in a matter of weeks or months. There is a great stigma and bias in the medical community that has inhibited the education and study of IBC. A lack of understanding of the disease, how it presents and how to treat it leaves many IBC patients facing misdiagnosis. Communication is a cornerstone of healthcare; this goes beyond the patient-provider dynamic. Education of IBC must be a grassroots initiative. There should be no barrier to care in the diagnosis, treatment, study and survivorship of inflammatory Breast Cancer. It is not just an oncologist\'s lesson to learn, but that of all providers in healthcare. In this chapter you will hear how 4 women who were diagnosed with IBC faced the difficult tasks of navigating through the healthcare system on their own and came out on the other side using their experience to help others. In conclusion, in defining the evolving roles of Patient Advocacy in IBC over the past 25 years, we examine what has been done, along with its challenges, and what work still remains from the perspectives of different patient advocates.

The telomere repetitive TTAGGG motif at the ends of chromosomes, serves to preserve genomic integrity and chromosomal stability. In turn, genomic instability is a hallmark of cancer-implicating telomere disturbance. Prostate cancer (PCa) shows significant ancestral disparities, with men of African ancestry at the greatest risk for aggressive disease and associated genomic instability. Yet, no study has explored the role of telomere length (TL) with respect to ancestrally driven PCa health disparities. Patient- and technically-matched tumour-blood whole genome sequencing data for 179 ancestrally defined treatment naïve PCa patients (117 African, 62 European), we assessed for TL (blood and tumour) associations. We found shortened tumour TL to be associated with aggressive PCa presentation and elevated genomic instabilities, including percentage of genome alteration and copy number gains, in men of African ancestry. For European patients, tumour TL showed significant associations with PCa driver genes PTEN, TP53, MSH2, SETBP1 and DDX11L1, while shorter blood TL (< 3200 base pairs) and tumour TL (< 2861 base pairs) were correlated with higher risk for biochemical recurrence. Concurring with previous studies linking TL to PCa diagnosis and/or prognosis, for the first time we correlated TL differences with patient ancestry with important implications for future treatments targeting telomere dysfunction.

BACKGROUND: Definitions of aggressive MS employ clinical and MR imaging criteria to identify highly active, rapidly progressing disease courses. However, the degree of overlap between clinical and radiological parameters and biochemical markers of CNS injury is not fully understood. Aim of this cross-sectional study was to match clinical and MR imaging hallmarks of aggressive MS to serum/CSF markers of neuroaxonal and astroglial injury (neurofilament light chain (sNfL, cNfL), and glial fibrillary acidic protein (sGFAP, cGFAP)).
METHODS: We recruited 77 patients with relapsing-remitting MS (RRMS) and 22 patients with clinically isolated syndrome. NfL and GFAP levels in serum and CSF were assessed using a single-molecule-array HD-1-analyzer. A general linear model with each biomarker as a dependent variable was computed. Clinical and imaging criteria of aggressive MS, as recently proposed by the ECTRIMS Consensus Group, were modeled as independent variables. Other demographic, clinical or laboratory parameters, were modeled as covariates. Analyses were repeated in a homogenous subgroup, consisting only of newly diagnosed, treatment-naïve RRMS patients presenting with an acute relapse.
RESULTS: After adjusting for covariates and multiplicity of testing, sNfL and cNfL concentrations were strongly associated with the presence of ≥2 gadolinium-enhancing lesions (psNfL = 0.00008; pcNfL = 0.004) as well as the presence of infratentorial lesions on MRI (psNfL = 0.0003; pcNfL < 0.004). No other clinical and imaging criteria of aggressive MS correlated significantly with NfL or GFAP in serum and CSF. In the more homogeneous subgroup, sNfL still was associated with the presence of ≥2 gadolinium-enhancing lesions (psNfL = 0.001), presence of more than 20 T2-lesions (psNfL = 0.049) as well as the presence of infratentorial lesions on MRI (psNfL = 0.034), while cNfL was associated with the presence of ≥2 gadolinium-enhancing lesions (psNfL = 0.011) and presence of more than 20 T2-lesions (psNfL = 0.029).
CONCLUSIONS: Among proposed risk factors for an aggressive disease course, MRI findings but not clinical characteristics correlated with sNfL and cNfL as a marker of neuroaxonal injury and should be given appropriate weight considering MS prognosis and therapy. No significant correlation was detected for GFAP alone.

Potential oncogene cleavage and polyadenylation specific factor 4 (CPSF4) has been linked to several cancer types. However, little research has been conducted on its function in prostate cancer (PCa). In benign, incidental, advanced, and castrate resistant PCa (CRPCa) patient samples, protein expression of CPSF4 was examined on tissue microarray (TMAs) of 353 PCa patients using immunohistochemistry. Using the \'The Cancer Genome Atlas\' Prostate Adenocarcinoma (TCGA PRAD) database, significant correlations were found between high CPSF4 expression and high-risk genomic abnormalities such as ERG-fusion, ETV1-fusion, and SPOP mutations. Gene Set Enrichment Analysis (GSEA) of CPSF4 revealed evidence for the increase in biological processes such as cellular proliferation and metastasis. We further examined the function of CPSF4 in vitro and confirmed CPSF4 clinical outcomes and its underlying mechanism. Our findings showed a substantial correlation between Gleason groups and CPSF4 protein expression. In vitro, CPSF4 knockdown reduced cell invasion and migration while also causing G1 and G2 arrest in PC3 cell lines. Our findings demonstrate that CPSF4 may be used as a possible biomarker in PCa and support its oncogenic function in cellular proliferation and metastasis.

Primary penile lymphomas are extremely rare. They are aggressive neoplasms that can present as double-or triple-hit lymphomas, and because the associate with a high risk of central nervous system dissemination, treatment consists of high-dose chemotherapy regimens plus intrathecal prophylaxis. Pathology can be confused with squamous cell carcinoma of the penis, leading to inappropriate treatments and unnecessary amputations. We report the case of a patient diagnosed with clinical Stage IV penile non-Hodgkin lymphoma that was treated with a complete and durable response. In addition, we review the available literature on penile lymphoma.

UNASSIGNED: Lung cancer is the leading cause of cancer death worldwide and the majority of the patients have advanced/metastatic disease on presentation. In clinical practice, several biomarkers and clinical factors are taken into account when choosing the best treatment option in advanced non-small-cell lung cancer (NSCLC). One potential marker may be tumor burden (TB). However, this concept is not specifically defined in NSCLC, and usually, it is used as a synonymous for aggressive disease.
UNASSIGNED: A non-systematic literature review was conducted. We searched for eligible randomized controlled trials from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials with a cutoff at February 2021. The keywords included non-small-cell lung cancer, tumor burden, aggressive disease, prognosis biomarker, predictive biomarker, and immunotherapy.
UNASSIGNED: This review addresses the definition of TB in advanced NSCLC, the pathophysiology of high TB lesions, and the role of TB as a prognosis biomarker.
UNASSIGNED: The concept of aggressive disease, as high tumor burden definition, remains poorly defined and rarely considered in clinical research or clinical practice in oncology. The identification of this subgroup of patients could be interesting for defining and optimizing a more aggressive treatment strategy.

DNA methylation plays important roles in prostate cancer (PCa) development and progression. African American men have higher incidence and mortality rates of PCa than other racial groups in U.S. The goal of this study was to identify differentially methylated CpG sites and genes between clinically defined aggressive and nonaggressive PCa in African Americans. We performed genome-wide DNA methylation profiling in leukocyte DNA from 280 African American PCa patients using Illumina MethylationEPIC array that contains about 860K CpG sties. There was a slight increase of overall methylation level (mean β value) with the increasing Gleason scores (GS = 6, GS = 7, GS ≥ 8, P for trend = 0.002). There were 78 differentially methylated CpG sites with P < 10-4 and 9 sites with P < 10-5 in the trend test. We also found 77 differentially methylated regions/genes (DMRs), including 10 homeobox genes and six zinc finger protein genes. A gene ontology (GO) molecular pathway enrichment analysis of these 77 DMRs found that the main enriched pathway was DNA-binding transcriptional factor activity. A few representative DMRs include HOXD8, SOX11, ZNF-471, and ZNF-577. Our study suggests that leukocyte DNA methylation may be valuable biomarkers for aggressive PCa and the identified differentially methylated genes provide biological insights into the modulation of immune response by aggressive PCa.

UNASSIGNED: Recurrent respiratory papillomatosis can present with a highly variable clinical course. The disease can cause serious morbidity and can be fatal because of airway obstruction. We examined whether the age of onset, gender, human immunodeficiency virus (HIV) infection and dysplasia on analysis of histological specimens were predictive of an aggressive disease course.
UNASSIGNED: To conduct an audit of all patients presenting with Recurrent Respiratory Papillomatosis at our institution and to determine if an earlier age of onset, gender, HIV and dysplasia are predictive factors for an aggressive disease course.
UNASSIGNED: A total of 202 clinical records and histological reports were reviewed at a quaternary-level hospital in Durban, South Africa. The disease was defined as juvenile onset (< 18 years) or adult onset (≥ 18 years). Aggressive disease was defined as a disease requiring 10 or more surgical debulkings in total and or extralaryngeal papilloma.
UNASSIGNED: A total of 184 patients were of juvenile onset and 18 were of adult onset. In the juvenile onset group, a total of 97 patients (52.8%) had aggressive disease. In the juvenile onset group, a later age of onset was associated with less aggressive disease (odds ratio [OR] = 0.77, p < 0.05). There were 20 (10.9%) HIV-positive patients. HIV infection was a predictor of aggressive disease (OR = 3, p < 0.029). Analysis of histological reports revealed that 39 (21.2%) of patients had dysplasia. Dysplasia was a predictor of aggressive disease (OR = 9.96, p < 0.05%). In the adult onset group, only two patients (11.1%) had aggressive disease.
UNASSIGNED: An earlier age of onset, HIV infection and dysplasia were predictors of aggressive disease in the juvenile onset group.

Most of screening-detected prostate cancer (PCa) are indolent and not lethal. Biomarkers that can predict aggressive diseases independently of clinical features are needed to improve risk stratification of localized PCa patients and reduce overtreatment. We aimed to identify leukocyte DNA methylation differences between clinically defined aggressive and non-aggressive PCa. We performed whole genome DNA methylation profiling in leukocyte DNA from 287 PCa patients with Gleason Score (GS) 6 and ≥8 using Illumina 450k methylation arrays. We observed a global hypomethylation in GS≥8 patients compared to GS=6 PCa patients; in contrast, the methylation level in core promoter and exon 1 region was significantly higher in GS≥8 patients than GS=6 PCa. We then performed 5-fold cross validated random forest model training on 1,459 differentially methylated CpG Probes (DMPs) with false discovery rate (FDR) <0.01 between GS=6 and GS≥8 groups. The power of the predictive model was further reinforced by ranking the DMPs with Decreased Gini and re-train the model with the top 97 DMPs (Testing AUC=0.920, predict accuracy =0.847). In conclusion, we identified a CpG methylation signature in leukocyte DNA that is associated with aggressive clinical features of PCa at diagnosis.

Increasing evidence suggests a role of epigenetic mechanisms at chromosome 8q24, an important cancer genetic susceptibility region, in prostate cancer. We investigated whether MYC DNA methylation at 8q24 (six CpG sites from exon 3 to the 3\' UTR) in prostate tumor was associated with tumor aggressiveness (based on Gleason score, GS), and we incorporated RNA expression data to investigate the function. We accessed radical prostatectomy tissue for 50 Caucasian and 50 African American prostate cancer patients at the University of Maryland Medical Center, selecting an equal number of GS 6 and GS 7 cases per group. MYC DNA methylation was lower in tumor than paired normal prostate tissue for all six CpG sites (median difference: -14.74 to -0.20 percentage points), and we observed similar results for two nearby sites in The Cancer Genome Atlas (p < 0.0001). We observed significantly lower methylation for more aggressive (GS 7) than less aggressive (GS 6) tumors for three exon 3 sites (for CpG 212 (chr8:128753145), GS 6 median = 89.7%; GS 7 median = 85.8%; p-value = 9.4 × 10-4). MYC DNA methylation was not associated with MYC expression, but was inversely associated with PRNCR1 expression after multiple comparison adjustment (q-value = 0.04). Findings suggest that prostate tumor MYC exon 3 hypomethylation is associated with increased aggressiveness.