Association of pre-chemotherapy peripheral blood pro-inflammatory and coagulation factors with reduced relative dose intensity in women with breast cancer.

BACKGROUND: Chemotherapy decreases the risk of relapse and mortality in early-stage breast cancer (BC), but it comes with the risk of toxicity. Chemotherapy efficacy depends on relative dose intensity (RDI), and an RDI < 85% is associated with worse overall survival. The pro-inflammatory (interleukin (IL)-6, C-reactive protein (CRP)) and coagulation factors (D-dimer) serve as biomarkers of aging. The purpose of this study is to determine if these biomarkers are associated with reduced RDI in women with stage I-III BC. METHODS: This study enrolled women with stage I-III BC. Prior to adjuvant or neoadjuvant chemotherapy, peripheral blood was collected for biomarker measurement. Dose reductions and delays were captured and utilized to calculate the RDI delivered. Univariate and multivariate analyses were performed to describe the association between pre-chemotherapy IL-6, CRP, and D-dimer levels and an RDI < 85%, controlling for relevant tumor and patient factors (age, stage, receptor status, chemotherapy regimen, and pre-chemotherapy physical function and comorbidity). RESULTS: A total of 159 patients (mean age 58 years, range 30-81, SD 11.3) with stage I-III BC were enrolled. An RDI < 85% occurred in 22.6% (N = 36) of patients and was associated with higher pre-chemotherapy IL-6 (OR 1.14, 95% CI 1.04-1.25; p = 0.006) and D-dimer (OR 2.32, 95% CI 1.27-4.24; p = 0.006) levels, increased age (p = 0.001), increased number of comorbidities (p = 0.01), and decreased physical function by the Medical Outcomes Survey Activities of Daily Living (ADL) Scale (p = 0.009) in univariate analysis. A multivariate model, including two biomarkers (IL-6 and D-dimer), age, ADL, BC stage, and chemotherapy regimen, demonstrated a significant association between the increased biomarkers and reduced RDI < 85% (OR 2.54; p = 0.04). CONCLUSIONS: Increased pre-chemotherapy biomarkers of aging (IL-6 and D-dimer) are associated with reduced RDI (<85%). Future studies are underway to validate these findings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01030250 . Registered on 3 November 2016.

Association of Pre-Chemotherapy Peripheral Blood Pro-Inflammatory and Coagulation Factors with Physical Function in Women with Breast Cancer.

BACKGROUND: Pro-inflammatory and coagulation factors serve as biomarkers of aging and functional reserve. The purpose of this study was to determine if pro-inflammatory (interleukin-6 [IL-6], C-reactive protein [CRP]), and coagulation (D-dimer) factors were associated with pre-chemotherapy functional status in women with stage I-III breast cancer. PATIENTS AND METHODS: Prior to chemotherapy initiation in patients with stage I-III breast cancer, the following was captured: IL-6, CRP, D-dimer blood levels, and physical function measures including activities of daily living (ADL, subscale of Medical Outcomes Study Physical Health); instrumental activities of daily living (IADL, subscale of the Older Americans Resources and Services Program); Timed Up and Go (TUG); physician-rated Karnofsky Performance Status (KPS); and self-rated KPS. The association of these biomarkers with physical function measures was evaluated. RESULTS: One hundred sixty patients (mean age 58.3 years, range 30-81 years) with stage I-III breast cancer (stages I [n = 34; 21.5%], II [n = 88; 55.7%], III [n = 36; 22.8%]) were enrolled. The group with poorest physical function (defined by ADL <70, IADL <14, and TUG ≥10 seconds) had higher levels of IL-6 (p = .05), D-dimer (p = .0004), and CRP (p = .05). There was no significant association between these biomarkers and KPS. Patients with at least two biomarkers in the highest quartile were more likely to have poorer physical function (odds ration [OR] 18.75, p < .001). In multivariate analysis adjusting for age, stage, number of comorbidities, and body mass index, the association remained (OR 14.6, p = .002). CONCLUSION: Pre-chemotherapy biomarkers of aging are associated with poorer physical function among patients with breast cancer across the aging spectrum. The Oncologist 2017;22:1189-1196 IMPLICATIONS FOR PRACTICE: Commonly used physical function assessment tools may not reflect the diverse nature of physical function and risk for chemotherapy toxicity, particularly in older adults. No laboratory test reflects functional reserve. Pro-inflammatory and coagulation factors, such as IL-6, CRP, and D-dimer, can serve as biomarkers of aging and physical function; however, few studies have evaluated their utility in patients with cancer. This study was designed to understand the association between pre-chemotherapy biomarkers and physical function in women with early stage breast cancer undergoing adjuvant chemotherapy. Results indicate that elevated pre-chemotherapy levels in two of the three peripheral biomarkers are associated with the poorest physical function among patients with breast cancer across the aging spectrum.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, a mimicker of malignancy: a case report and review of the literature.

BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids is a clinically and radiographically distinct inflammatory syndrome affecting multiple structures of the brain, including the cerebellum, brainstem, and spinal cord. The clinical presentation can be variable, including ataxia, nystagmus, dysarthria, dysphagia, and other subacute brainstem, cranial nerve, or cerebellar symptoms. These symptoms can be subacute to chronic, episodic, and progressive, making the diagnosis challenging. The hallmark radiographic magnetic resonance imaging findings are gadolinium-enhancing punctate lesions predominantly "peppering" the pons in a perivascular pattern. CASE PRESENTATION: Here, we describe a case and literature review of a 74-year-old Caucasian male who presented with subacute symptoms of ataxia, diplopia, and generalized fatigue. Physical examination was notable for horizontal nystagmus and wide-based gait. Magnetic resonance imaging revealed angiocentric enhancement predominantly in the brainstem and cerebellum, with involvement of the basal ganglia, thalami, and supratentorial white matter. Meanwhile, a screening computed tomography scan demonstrated a right upper lobe mass with biopsy proving primary lung cancer. Biopsy of one of the brain lesions showed perivascular infiltrate primarily composed of CD3+ T cells, scattered CD20+ B cells, and no signs of malignancy. The patient was started on high-dose glucocorticoids followed by a maintenance regimen with rapid improvement clinically and radiographically. Given extensive work-up was negative, these clinical and radiographic findings were consistent with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. CONCLUSIONS: This case illustrates the difficulty of diagnosing chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, given its variable presentation, lack of specific laboratory findings, and poorly understood pathogenesis. We demonstrate a case that responded well to oral corticosteroid burst followed by a taper to the lowest corticosteroid dose clinically possible. Failure to recognize this syndrome could result in permanent central nervous system morbidity. Therefore, earlier recognition is crucial for this treatable condition.

Non-small cell lung cancer in the elderly: defining treatment options.

Lung cancer is the leading cause of cancer deaths in the Western countries. Recent advancements in the treatment of non-small cell lung cancer (NSCLC) have led to an improvement in outcomes, although 5-year survival rates remain about 15%. Moreover, the number of patients diagnosed and treated with lung cancer over the age of 65 years is growing. Despite this fact, elderly patients are infrequently included into clinical trials, which results in a limited amount of evidence-based options regarding therapy for the elderly. The limited data correlate directly with the lack of established treatment guidelines for elderly patients with NSCLC. In this article, we review both retrospective and prospective studies that help to define treatment of the elderly with early-stage, locally advanced, and metastatic NSCLC. Ultimately, increasing participation of the elderly within clinical trials is essential to firmly establish treatment regimens to increase survival while minimizing toxicity.

Helical tomotherapy for radiotherapy in esophageal cancer: a preferred plan with better conformal target coverage and more homogeneous dose distribution.

We compare different radiotherapy techniques-helical tomotherapy (tomotherapy), step-and-shoot IMRT (IMRT), and 3-dimensional conformal radiotherapy (3DCRT)-for patients with mid-distal esophageal carcinoma on the basis of dosimetric analysis. Six patients with locally advanced mid-distal esophageal carcinoma were treated with neoadjuvant chemoradiation followed by surgery. Radiotherapy included 50 Gy to gross planning target volume (PTV) and 45 Gy to elective PTV in 25 fractions. Tomotherapy, IMRT, and 3DCRT plans were generated. Dose-volume histograms (DVHs), homogeneity index (HI), volumes of lung receiving more than 10, 15, or 20 Gy (V(10), V(15), V(20)), and volumes of heart receiving more than 30 or 45 Gy (V(30), V(45)) were determined. Statistical analysis was performed by paired t-tests. By isodose distributions and DVHs, tomotherapy plans showed sharper dose gradients, more conformal coverage, and better HI for both gross and elective PTVs compared with IMRT or 3DCRT plans. Mean V(20) of lung was significantly reduced in tomotherapy plans. However, tomotherapy and IMRT plans resulted in larger V(10) of lung compared to 3DCRT plans. The heart was significantly spared in tomotherapy and IMRT plans compared to 3DCRT plans in terms of V(30) and V(45). We conclude that tomotherapy plans are superior in terms of target conformity, dose homogeneity, and V(20) of lung.