The impact of preexisting comorbidities on receipt of cancer therapy among women with Stage I-III breast cancer in the Detroit Research on Cancer Survivors cohort.

PURPOSE: Pre-existing comorbidities play an important role in choice of cancer treatment. We retrospectively evaluated the relationship between pre-existing comorbidities and receipt of local and systemic therapy in a cohort of Black women with Stage I-III breast cancer. METHODS: The study population for analysis included 1169 women with Stage I-III disease enrolled in the Detroit Research on Cancer Survivors (ROCS) cohort. Information on comorbidities, socio-demographic, and clinical variables were obtained from self-reported questionnaires and the cancer registry. Comorbidities were analyzed individually, and comorbidity burden was categorized as low (0-1), moderate (2-3) or high (≥4). We used logistic regression analysis to evaluate factors associated with receipt of local treatment (surgery ± radiation; N = 1156), hormonal (N = 848), and chemotherapy (N = 680). Adjusted models included variables selected a priori that were significant predictors in univariate analysis. RESULTS: Receipt of treatment was categorized into local (82.6%), hormonal (73.7%), and/or chemotherapy (79.9%). Prior history of arthritis and depression were both associated with a lower likelihood to receive local treatment, [odds ratio (OR), 95% confidence interval (CI), 0.66, 0.47-0.93, and 0.53, 0.36-0.78], respectively. Obesity was associated with higher likelihood of receiving hormonal therapy (OR: 1.64, 95% CI: 1.19, 2.26), and heart failure a lower likelihood (OR: 0.46, 95% CI: 0.23, 0.90). Older age (Ptrend <0.01) and increasing co-morbidity burden (Ptrend = 0.02) were associated with lower likelihood of receiving chemotherapy. CONCLUSION: History of prior co-morbidities has a potentially detrimental influence on receipt of recommended cancer-directed treatment among women with Stage I-III breast cancer.

Predictors of Definitive Treatment Interruptions of Long-Course Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer.

Introduction To identify predictors of definitive treatment interruptions (DTI) of the neoadjuvant long-course radiotherapy (LCRT) in locally advanced rectal cancer (LARC), and to determine their impact on clinical outcomes. Methods Patients with stage II-III LARC treated between 2009-2018 were retrospectively analyzed (n=101, median FU 49.5 months). Logistic regression models evaluated the impact of relevant clinical variables on grade 3 or greater (G3+) acute toxicity, definitive treatment interruption (DTI), pCR, and definitive ostomy (dOST) rates. The secondary outcomes were LRC, MFS, PFS, CSS, and OS. Results The incidences of grade 3 and 4 toxicities were 25.3%, and 1.1%, respectively. The most common G3+ toxicities were peri-anal dermatitis (14.7%) and diarrhea (7.4%), which were more frequent in females (p=0.040) and tumors close to the anal verge (p=0.019). In this study, 11 patients (10.9%) developed DTI, which was associated with these G3+ events (p<0.001). Resection occurred after 7.1 weeks (median, IQR:6.1-8.9). Downstaging occurred in 57.4% (17.8% pCR), 88% achieved negative margins and the dOST rate was 56.4%. The five-year LRC, MFS, PFS, CSS and OS were: 94.4%, 78.9%, 74.7%, 85.2% and 81.6%, respectively. DTI events did not impact any outcome. The factors associated with loco-regional failure were close/positive margins (p<0.001) and stage ypIII (p=0.002). Conclusions: Tumors close to the anal verge and female sex were associated with increased G3+ toxicity, which was predictive of DTI. The resultant partial/complete omission of the planned boost, however, dose did not increase the chance of LR. Further studies to clarify the benefit and optimal timing to deliver the boost are warranted, especially for positive margins.

A review of research on the intersection between breast cancer and cardiovascular research in the Women's Health Initiative (WHI).

Both obesity and metabolic syndrome are linked to increased incidence of type 2 diabetes, cardiovascular disease (CVD), and cancers of the breast (post-menopausal), and other obesity-related cancers. Over the past 50 years, the worldwide prevalence of obesity and metabolic syndrome has increased, with a concomitant higher incidence of associated co-morbidities and mortality. The precise mechanism linking metabolic syndrome to increased cancer incidence is incompletely understood, however, individual components of metabolic syndrome have been linked to increased breast cancer incidence and worse survival. There is a bidirectional relationship between the risk of CVD and cancer due to a high burden of shared risk factors and higher rates of CVD among cancer survivors, which may be impacted by the pro-inflammatory microenvironment associated with metabolic syndrome and cancer-directed therapies. The Women's Health Initiative (WHI) is an excellent resource to study a dual relationship between cancer and CVD (cardio-oncology) with extensive information on risk factors and long-term outcomes. The purpose of this review is to provide an overview of research on cardio-oncology conducted utilizing WHI data with focus on studies evaluating both breast cancer and CVD including shared risk factors and outcomes after cancer. The review also includes results on other obesity related cancers which were included in the analyses of breast cancer, articles looking at cancer after heart disease (reverse cardio-oncology) and the role of Clonal Hematopoiesis of Indeterminate Potential (CHIP) as a shared risk factor between CVD and cancer. A summary of pertinent WHI literature helps to delineate the direction of future research evaluating the relationship between CVD and other cancer sites, and provides information on the opportunity for other novel analyses within the WHI.

A Review of Research on Disparities in the Care of Black and White Patients With Cancer in Detroit.

Racial disparities in cancer incidence and outcomes are well-documented in the US, with Black people having higher incidence rates and worse outcomes than White people. In this review, we present a summary of almost 30 years of research conducted by investigators at the Karmanos Cancer Institute's (KCI's) Population Studies and Disparities Research (PSDR) Program focusing on Black-White disparities in cancer incidence, care, and outcomes. The studies in the review focus on individuals diagnosed with cancer from the Detroit Metropolitan area, but also includes individuals included in national databases. Using an organizational framework of three generations of studies on racial disparities, this review describes racial disparities by primary cancer site, disparities associated with the presence or absence of comorbid medical conditions, disparities in treatment, and disparities in physician-patient communication, all of which contribute to poorer outcomes for Black cancer patients. While socio-demographic and clinical differences account for some of the noted disparities, further work is needed to unravel the influence of systemic effects of racism against Black people, which is argued to be the major contributor to disparate outcomes between Black and White patients with cancer. This review highlights evidence-based strategies that have the potential to help mitigate disparities, improve care for vulnerable populations, and build an equitable healthcare system. Lessons learned can also inform a more equitable response to other health conditions and crises.

Heritable Susceptibility to Breast Cancer among African-American Women in the Detroit Research on Cancer Survivors Study.

BACKGROUND: African-American women have high rates of breast cancer associated with hereditary features. However, no studies have reported the prevalence of inherited variation across all genes known to be breast cancer risk factors among African-American patients with breast cancer not selected for high-risk characteristics. METHODS: We evaluated 182 African-American women diagnosed with invasive breast cancer in metropolitan Detroit via targeted capture and multiplex sequencing of 13 well-established breast cancer risk genes and five suggested breast cancer risk genes. RESULTS: We identified 24 pathogenic variants in 23 women [12.6%; 95% confidence interval (CI), 8.2%-18.4%] and five genes (BRCA2, BRCA1, ATM, RAD50, CDH1). BRCA1 and BRCA2 accounted for 58.3% of all pathogenic variants. An additional six pathogenic variants were found in suggested breast cancer risk genes (MSH6, MUTYH, NF1, BRIP1). CONCLUSIONS: The prevalence of germline pathogenic variants is relatively high among African-American patients with breast cancer unselected for high-risk characteristics across a broad spectrum of genes. IMPACT: This study helps to define the genomic landscape of breast cancer susceptibility in African-American women who could benefit from enhanced surveillance and screening.

Pomalidomide-Based Regimens for Treatment of Relapsed and Relapsed/Refractory Multiple Myeloma: Systematic Review and Meta-analysis of Phase 2 and 3 Clinical Trials.

INTRODUCTION: Pomalidomide (Pom) has demonstrated synergistic antiproliferative activity in combination regimens as a result of its distinct anticancer, antiangiogenic, and immunomodulatory effects. This review aimed to compare outcome measures of different Pom regimens for relapsed/refractory multiple myeloma. METHODS: A comprehensive literature search identified a total of 1374 studies. Thirty-five studies assessing 4623 subjects met the inclusion criteria: phase 2/3 trial, ≥ 2 prior lines of therapy, and clearly documented efficacy outcomes like overall response rate (ORR), overall survival, and progression-free survival. Statistical analyses for meta-analysis was performed by CMA version 3 and Cochrane Q statistics (P < .05 considered significant, I2 index for heterogeneity). A random effects model was used if there was significant heterogeneity (P ≥ .05 over I2 ≥ 50%). RESULTS: Pooled analysis showed ORR 47.1% across all Pom-based (2- and 3-drug) regimens. Stratified analysis for efficacy outcomes (pooled ORR [%] and mean progression-free survival [months]) are reported. With doublet regimen, Pom with low-dose dexamethasone (LoDex) was the most common regimen (35.7%, 6.1 months), and overall survival was 14.37 months. With triplet regimens, pooled ORR was 61.9% (I2 = 87.3%). These included bortezomib + Pom + LoDex (83.5%, 15.7 months), carfilzomib-Pom + LoDex (77.1%, 15.3 months), Pom + LoDex-bendamustine (74.2%), Pom-dexamethasone-daratumumab (64.5%), Pom + LoDex-cyclophosphamide (59.4%, 9.5 months), and Pom + LoDex-doxorubicin (32%). Leading adverse events were myelosuppression, with mean incidences of grade 3 or higher neutropenia, anemia, and thrombocytopenia of 47.6%, 26.5%, and 20.8%, respectively. Mean incidence of grade 3 or higher nonhematologic adverse events were infections 29.1%, pneumonia 13.8%, and fatigue 10%. CONCLUSION: Three-drug Pom regimens yielded double the response rates compared to Pom + LoDex (pooled ORR, 61.9% vs. 35.7%), with bortezomib + Pom + LoDex and carfilzomib-Pom + LoDex demonstrating better outcomes than other regimens.

Dual-Positive CD4/CD8 Primary Cutaneous Peripheral T-Cell Lymphoma Previously Classified as Mycosis Fungoides a Tumor D'Emblée.

Cutaneous peripheral T-cell lymphoma, not otherwise specified represents a "waste basket" of all cases that cannot be put into another of the categories of mature cutaneous T-cell lymphoma. Previously, the sudden multifocal development of cutaneous CD4 tumors without preceding a patch or plaque stage was classified as d'emblée form of mycosis fungoides (MF). Currently, the term "MF" reserved only for the classic Alibert-Bazin type characterized by the evolution of patches, plaques, and tumors or for variants showing a similar clinical course. The authors describe a 75-year-old white woman who presented with a solitary skin tumor in the right supraclavicular region, with no lymph node or systemic involvement. Local external beam radiation treatment resulted in a complete response. The patient relapsed after 5 months with new tumors in the left neck and left upper chest. Biopsy of the lesions showed a dermal infiltrate of atypical small- to medium-sized T-lymphocytes, and immunohistochemical staining showed coexpression of CD4/CD8 in a subset of these cells, which was confirmed with flow cytometry of the tumor. Although the patient had no preceding patch or plaque stage, the authors herein report this extremely rare case of CD4/CD8 dual-positive peripheral T-cell lymphoma, not otherwise specified presented as MF d'emblée and discuss the seldom similar cases published previously.

Evaluation of immunogenicity and protective efficacy of combination heat-killed immunogens from three entero-invasive bacteria in rabbit model.

Diarrhea is a very common health problem in both developing and developed countries. Among the major entero-invasive bacteria, Shigella, Salmonella and Campylobacter cause serious problems in different geographic regions. Recently we have shown immunogenicity and protective efficacy of heat killed multi-serotype Shigella immunogen in different animal models. In our present study, we have advanced our research by preparing a combination heat-killed immunogen of three different entero-invasive bacteria, Shigella, Salmonella and Campylobacter. After three doses on 0th, 14th and 28th day of oral immunization with tri-valent heat-killed (TVHK) immunogen in rabbit model, the immunogenicity was determined by differential count of white blood cells and immunoglobulin assay at various time points. During oral immunization differential count of lymphocytes increased where as polymorphonuclear leucocytes (PMN) count decreased. Serum IgG and IgA showed significant elevation during oral immunization and remained at a detectable value upto 120 days. Protection study was performed in both, in vitro and in vivo conditions, using bacteriocidal assay and rabbit ligated ileal loop model, respectively, which conferred protection against homologous bacteria. Moreover, immunoblot assay against whole cell lysate and lipopolysaccharide exhibited significant amount of antigen-specific immunoglobulins raised against three different bacteria which proved that proteins along with lipopolysaccharides played a pivotal role in immunogenicity and protective efficacy. This trivalent heat-killed immunogen could be a low-cost, simple, oral, non-living vaccine candidate for future use against invasive diarrhea.

Current status of knowledge, attitude and practice (KAP) and screening for cervical cancer in countries at different levels of development.

Cancer of the uterine cervix is a worldwide menace taking innumerable womens' lives. The literature is vast and a large number of studies have been conducted in this field. Analyses have shown significant differences exist in terms of screening and HPV testing facilities among high income and low to middle income countries. In addition, acute lack of awareness and knowledge among the concerned population is particularly noted in rural areas of the low income countries. A detailed review of Indian case studies revealed that early age of marriage and childbirth, multiparity, poor personal hygiene and low socio-economic status among others are the principal risk factors for this disease. This review concludes that a two pronged strategy involving strong government and NGO action is necessary to minimize the occurrence of cervical cancer especially in low and medium income countries.

Socio-demographic and behavioural risk factors for cervical cancer and knowledge, attitude and practice in rural and urban areas of North Bengal, India.

BACKGROUND: Cervical cancer is common among women worldwide. A multitude of risk factors aggravate the disease. This study was conducted to: (1) determine the prevalence and (2) make a comparative analysis of the socio-demographic and behavioural risk factors of cervical cancer and knowledge, attitude and practice between rural and urban women of North Bengal, India. STUDY DESIGN: Community-based cross-sectional study. METHODS: A survey (first in North Bengal) was conducted among 133 women in a rural area (Kawakhali) and 88 women in an urban slum (Shaktigarh) using predesigned semi-structured questionnaires. The respondents were informed of the causes (including HPV), signs and symptoms, prevention of cervical cancer and treatment, and the procedure of the PAP test and HPV vaccination. RESULTS: The prevalence of risk factors like multiparity, early age of marriage, use of cloth during menstruation, use of condom and OCP, early age of first intercourse was 37.2%, 82%, 83.3%, 5.4%, 15.8% and 65.6% respectively. Awareness about the cause, signs and symptoms, prevention of cervical cancer, PAP test and HPV vaccination was 3.6%, 6.3%, 3.6%, 9.5% and 14.5% respectively. Chi-square testing revealed that in the study population, significant differential at 5% exists between rural and urban residents with respect to number of children, use of cloth/sanitary napkins, family history of cancer and awareness regarding causes of cervical cancer. Regarding KAP, again using chi-square tests, surprisingly, level of education is found to be significant for each element of KAP in urban areas in contrast to complete absence of association between education and elements of KAP in rural areas. CONCLUSIONS: A large number of risk factors were present in both areas, the prevalence being higher in the rural areas. The level of awareness and role of education appears to be insignificant determinants in rural compared to urban areas. This pilot study needs to be followed up by large scale programmes to re-orient awareness campaigns, especially in rural areas.