National Recommendations against Prostate Specific Antigen Screening versus Statewide Medicaid Expansion Initiatives: A Battle of the Titans.

PURPOSE: Medicaid expansion under the Patient Protection and Affordable Care Act occurred almost concurrently with 2012 U.S. Preventive Services Task Force recommendations against prostate specific antigen screening. Here the relative influence on prostate specific antigen screening rates by 2 concurrent and opposing system-level policy initiatives is investigated: improved access to care and change in clinical practice guidelines. MATERIALS AND METHODS: Behavioral Risk Factor Surveillance System data from years 2012 to 2018 were analyzed for trends in self-reported prostate specific antigen screening and insurance coverage. Subanalyses included state Medicaid expansion status and respondent federal poverty level. Multivariable logistic regression was performed to evaluate factors associated with prostate specific antigen screening. RESULTS: From 2012 to 2018 prostate specific antigen screening predominantly declined with a notable exception of an increase of 7.3% for men at <138% federal poverty level between 2011 and 2013 in early expansion states. Initial increases did not continue, and screening trends mirrored those of nonexpansion states by 2018. Notably, 2014 planned expansions states did not follow this trend with minimal change between 2015 and 2017 compared to declines in early expansion states and nonexpansion states (-0.4% vs -6.7% and -8.6%, respectively). CONCLUSIONS: Medicaid expansion was associated with increased rates of insured men at <138% federal poverty level from 2012 to 2018 in early expansion states. In this group, initial increases in prostate specific antigen screening were not durable and followed the trend of reduced screening seen across the United States. In planned expansions states the global drop in prostate specific antigen screening from 2016 to 2018 was offset in men at <138% federal poverty level by expanding access to care. Nonexpansion states showed a steady decline in prostate specific antigen screening rates. This suggests that policy such as U.S. Preventive Services Task Force recommendations against screening competes with and often outmatches access to care.

Disability-Adjusted Life-Years Due to Stroke in Kenya.

BACKGROUND: There is little information on stroke morbidity in Kenya to inform health care planning. The disability-adjusted life-years (DALYs) are a time-based measure of health status that incorporates both disability and mortality. METHODS: This was a multicenter prospective study in Kenya's public tertiary hospitals conducted in 2015-2017. Data on sex, age, and global disability outcome were collected and used to calculate the sum of years of life lost prematurely due to stroke (YLL), the years of healthy life lost due to disability (YLD), and the DALYs. RESULTS: Up to 719 adult stroke patients participated in the study. The peak age group for stroke was 60-64 years, with ischemic stroke accounting for 56.1% of the stroke cases. After 1-year follow-up, the YLD were 2,402.50, YLL were 5,335.99, and the DALYs were 7,738.49. YLD contributed 31% of the total DALYs. The DALYs varied by sex (male: 2,835.79; female: 4,902.70 years) and by stroke type (ischemic stroke: 4,652.98; hemorrhagic stroke: 3,085.51). The young age group (< 45 years) bore a greater burden accounting for 35.6% of the total DALYs. CONCLUSION: The YLD, YLL, and DALYs observed reinforce the need for targeted prevention of risk factors and comprehensive stroke care initiatives in Kenya.

Prostate cancer navigation: initial experience and association with time to care.

OBJECTIVE: To evaluate factors associated with use of patient navigation in a prostate cancer population and identify whether navigation is associated with prolonged time to care. Cancer patient navigation has been shown to improve access to cancer screening, diagnosis, and treatment, but little is known about patient navigation in prostate cancer care. METHODS: All men diagnosed with localized prostate cancer between 2009 and 2015 were abstracted from the MaineHealth multi-specialty tumor registry. Regression analyses controlling for patient-, disease-, and system-level factors evaluated characteristics associated with navigation utilization. The association between navigation utilization, barriers to care, and longer time to treatment was assessed with Cox proportional hazards regression. RESULTS: Of the patient population (n = 1587), 85% of men were navigated. Navigation use was associated with earlier year of diagnosis, treatment by a high-volume urologist, and lower risk disease (p < 0.05). Treatment delay was associated with low-risk disease (vs: intermediate OR 0.62, 95% CI 0.46-0.85 and high OR 0.16, 95% CI 0.1-0.25) and receipt of navigation services (OR 1.65, 95% CI 1.12-2.45) but not distance to care, insurance, or treatment choice. CONCLUSIONS: We observed that patients with low-risk prostate cancer were more likely to utilize navigation, but traditional barriers to care were not associated with utilization. Navigation was associated with longer time to treatment, which likely reflects clinically appropriate delays associated with greater shared decision making. Time to treatment may not be the ideal metric for evaluating navigation in prostate cancer; shared decision making, patient satisfaction, and psychosocial outcomes may be more appropriate.

Factors influencing survival among Kenyan children diagnosed with endemic Burkitt lymphoma between 2003 and 2011: A historical cohort study.

Discovering how to improve survival and establishing clinical reference points for children diagnosed with endemic Burkitt lymphoma (eBL) in resource-constrained settings has recaptured international attention. Using multivariate analyses, we evaluated 428 children with eBL in Kenya for age, gender, tumor stage, nutritional status, hemoglobin, lactate dehydrogenase (LDH), Epstein-Barr virus (EBV) and Plasmodium falciparum prior to induction of chemotherapy (cyclophosphamide, vincristine, methotrexate and doxorubicin) to identify predictive and prognostic biomarkers of survival. During this 10 year prospective study period, 22% died in-hospital and 78% completed six-courses of chemotherapy. Of those, 16% relapsed or died later; 31% achieved event-free-survival; and 31% were lost to follow-up; the overall one-year survival was 45%. After adjusting for covariates, low hemoglobin (<8 g/dL) and high LDH (>400 mU/ml) were associated with increased risk of death (adjusted Hazard Ratio (aHR) = 1.57 [0.97-2.41]) and aHR = 1.84, [0.91-3.69], respectively). Anemic children with malaria were 3.55 times more likely to die [1.10-11.44] compared to patients without anemia or malarial infection. EBV load did not differ by tumor stage nor was it associated with survival. System-level factors can also contribute to poor outcomes. Children were more likely to die when inadvertently overdosed by more than 115% of the correct dose of cyclophosphamide (a HR = 1.43 [0.84-2.43]) or doxorubicin (a HR = 1.25, [0.66-2.35]), compared with those receiving accurate doses of the respective agent in this setting. This study codifies risk factors associated with poor outcomes for eBL patients in Africa and provides a benchmark by which to assess improvements in survival for new chemotherapeutic approaches.

Treatment factors affecting outcomes in HIV-associated non-Hodgkin lymphomas: a pooled analysis of 1546 patients.

Limited comparative data exist for the treatment of HIV-associated non-Hodgkin lymphoma. We analyzed pooled individual patient data for 1546 patients from 19 prospective clinical trials to assess treatment-specific factors (type of chemotherapy, rituximab, and concurrent combination antiretroviral [cART] use) and their influence on the outcomes complete response (CR), progression free survival (PFS), and overall survival (OS). In our analysis, rituximab was associated with a higher CR rate (odds ratio [OR] 2.89; P < .001), improved PFS (hazard ratio [HR] 0.50; P < .001), and OS (HR 0.51; P < .0001). Compared with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), initial therapy with more dose-intense regimens resulted in better CR rates (ACVBP [doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisolone]: OR 1.70; P < .04), PFS (ACVBP: HR 0.72; P = .049; "intensive regimens": HR 0.35; P < .001) and OS ("intensive regimens": HR 0.54; P < .001). Infusional etoposide, prednisone, infusional vincristine, infusional doxorubicin, and cyclophosphamide (EPOCH) was associated with significantly better OS in diffuse large B-cell lymphoma (HR 0.33; P = .03). Concurrent use of cART was associated with improved CR rates (OR 1.89; P = .005) and trended toward improved OS (HR 0.78; P = .07). These findings provide supporting evidence for current patterns of care where definitive evidence is unavailable.

Icrucumab, a fully human monoclonal antibody against the vascular endothelial growth factor receptor-1, in the treatment of patients with advanced solid malignancies: a Phase 1 study.

BACKGROUND: IMC-18F1 (icrucumab), a human monoclonal antibody against vascular endothelial growth factor receptor-1 (VEGFR-1), potently inhibits ligand-dependent phosphorylation of VEGFR-1 and downstream signaling, making icrucumab an attractive candidate for antitumor activity. OBJECTIVES: The primary objective was to determine the safety profile and maximum tolerated dose of icrucumab in patients with advanced solid tumors that were previously unresponsive to standard therapy or for which no standard therapy was available. METHODS: In this open-label, dose-escalation, Phase 1 study, patients received icrucumab intravenously weekly at 2, 3, 6, and 12 mg/kg (Cohorts 1-4), every other week (q2w) at 15 mg/kg (Cohort 5), or every third week at 20 mg/kg (Cohort 6). Patients received icrucumab until evidence of progressive disease or other withdrawal criteria were met. RESULTS: Twenty-six patients received icrucumab. The most common adverse events were fatigue, nausea, peripheral edema, anemia, dyspnea, and vomiting. No dose-limiting toxicities (DLTs) were observed in Cohorts 1-5. Two DLTs were observed in Cohort 6 (anemia and hyponatremia), and enrollment was stopped. No patient demonstrated an immunogenic response. Overall, icrucumab exhibited nonlinear pharmacokinetics at doses >6 mg/kg. Six patients (23.1 %) achieved stable disease with median duration of 11.1 weeks (range = 10.3-18.7 weeks); tumor types were thyroid, melanoma, colorectal (3 patients), and small-cell lung cancers. CONCLUSIONS: Icrucumab was safely administered weekly at doses of 2-12 mg/kg and q2w at a dose of 15 mg/kg with no DLTs. Based on achievement of stable disease, icrucumab has potential for antitumor activity against advanced solid tumors.

"Don't know" and accuracy of breast cancer risk perceptions among Appalachian women attending a mobile mammography program: implications for educational interventions and patient empowerment.

Risk perceptions are motivating factors for engaging in preventive health behaviors. Yet, almost one third of women attending a mobile mammography program targeted to rural and medically underserved Appalachian women respond "don't know" to their perceived 5-year risk of breast cancer. This study used cross-sectional data from women aged >40 years participating in Bonnie's Bus Mammography Screening and Preventive Care Survey from 2009 to 2011 to identify factors associated with "don't know" responses and accuracy of perceived risk according to constructs of the health belief model and sociodemographic characteristics. Women who responded "don't know" were more likely to be less educated, of lower income, insured by Medicaid, and less knowledgeable about breast cancer. Conversely, women who accurately perceived their risk were more likely to be of higher education, more knowledgeable about breast cancer, and have a family history of breast cancer. However, women with a high objective 5-year risk of breast cancer and older age at childbirth or were nulliparous were less likely to accurately perceive their risk. These findings suggest that women who indicate "don't know" responses and hold inaccurate risk perceptions are a population vulnerable to health disparities and may benefit from educational interventions focused on improving breast cancer knowledge and perceptions to empower them to take an active role in their preventive health and make informed decisions based on their individual level of risk.

Seeking American Society of Clinical Oncology-Quality Oncology Practice Initiative (ASCO-QOPI) certification in a northern New England rural health system and cancer care network.

In 2006 following several years of preliminary study, the American Society of Clinical Oncology (ASCO) launched the Quality Oncology Practice Initiative (QOPI). This cancer-focused quality initiative evolved considerably over the next decade-and-a-half and is expanding globally. QOPI is undoubtedly the leading standard-bearer for quality cancer care and contemporary medical oncology practice. The program garners attention and respect among federal programs, private insurers, and medical oncology practices across the nation. The MaineHealth Cancer Care Network (MHCCN) has undergone expansive growth since 2017. The network provides cancer care to more than 70% of the cases in Maine in a largely rural health system in Northern New England. In fall 2020, the MHCCN QOPI project leadership, following collaborative discussions with the ASCO-QOPI team, elected to proceed with a health system-cancer network-wide QOPI certification. Key themes emerged over the course of our two-year journey including: (1) Developing a highly interprofessional team committed to the project; (2) Capitalizing on a single electronic medical record for data transmission to CancerLinQ; (3) Prior experience, especially policy development, in other cancer-focused accreditation programs across the network; and (4) Building consensus through quarterly stakeholder meetings and awarding Continuing Medical Education (CME) and American Board of Medical Specialists (ABMS) Maintenance of Certification (MOC) credits to oncologists. All participants demonstrated a genuine spirit to work together to achieve certification. We report our successful journey seeking ASCO-QOPI certification across our network, which to our knowledge is the first-of-its-kind endeavor.

Do Appalachian women attending a mobile mammography program differ from those visiting a stationary mammography facility?

To compare the characteristics (demographic, access to care, health-related behavioral, self and family medical history, psychosocial) of women aged 40 years and above who utilize a mobile mammography unit with those women aged 40 years and above who obtain mammography screening at a stationary facility. A cross-sectional study design was used with participant cohorts comprised of women age 40 years and above throughout West Virginia (WV) who utilized mobile mammography unit to get mammogram and those who had mammography screening at the stationary facility and completed the Mammography Screening and Preventive Care Survey. A total of 1,161 women who utilized the mobile mammography unit and 1,104 women who utilized stationary facility were included in the analysis. In logistic regression after adjusting for all the variables, women who utilized mobile mammography unit were more likely to be in age group 40-49, with lower income, with no health insurance coverage, not visit doctor or obstetrician/gynecologist (OB/GYN) in the past year, not adherent to clinical breast exam and mammography screening guidelines, with lower perceived five-year risk of developing breast cancer and with high knowledge about mammography screening. Women who utilize mobile unit are not adherent to mammography screening guidelines thereby suggesting that the mobile mammography unit is indeed reaching a rural vulnerable population who may not routinely access preventive health services. Financial and insurance constraints, as well as access to medical care, restricted WV women from receiving mammography screening from the stationary screening facilities.

Are obese women more likely to participate in a mobile mammography program?

Mobile mammography services are typically offered as a means to increase access and adherence to mammography screenings. As mobile mammography becomes a viable strategy to increase screening, a 3 year study of such a state-wide program in WV found surprisingly high rates of obesity within the study population. Thus, the objectives were to: (1) describe the demographic characteristics and comorbidities of women who utilized the WV program, and (2) determine the association between body mass index (BMI) and personal health and screening history, preventive care and wellness behaviors, nutrition and exercise behaviors, and demographics. Data collected from 1,099 women, age 40 and above, were analyzed using descriptive statistics, bivariate analyses, and a multivariate regression model. The majority (60.4 %) were married, had an income <$25,000 (59.2 %), and had health insurance (53.5 %). Major comorbidities were hypertension (49 %) and high cholesterol (43.9 %). Based on BMI scores, 884 participants were either overweight (26.6 %), mildly obese (27.7 %), moderately obese (15.1 %), or severely obese (11.1 %). Bivariate analyses indicated that increasing BMI was significantly associated with factors such as having hypertension or diabetes, limited daily activities, perceived health, and not smoking or drinking. The regression model was significant (p < 0.001; R2 = 0.425) indicating that women who engaged in preventive care behaviors were less likely to be obese than those who did not. The WV mobile mammography program appeared to attract women who were disproportionately obese and had multiple comorbidities, thus providing a great opportunity for targeted interventions related to improving preventive care and screening behaviors.

Targeting the secreted RGDKGE collagen fragment reduces PD­L1 by a proteasome­dependent mechanism and inhibits tumor growth.

Structural alterations of collagen impact signaling that helps control tumor progression and the responses to therapeutic intervention. Integrins represent a class of receptors that include members that mediate collagen signaling. However, a strategy of directly targeting integrins to control tumor growth has demonstrated limited activity in the clinical setting. New molecular understanding of integrins have revealed that these receptors can regulate both pro­ and anti­tumorigenic functions in a cell type­dependent manner. Therefore, designing strategies that block pro­tumorigenic signaling, without impeding anti­tumorigenic functions, may lead to development of more effective therapies. In the present study, evidence was provided for a novel signaling cascade in which ß3­integrin­mediated binding to a secreted RGDKGE­containing collagen fragment stimulates an autocrine­like signaling pathway that differentially governs the activity of both YAP and (protein kinase­A) PKA, ultimately leading to alterations in the levels of immune checkpoint molecule PD­L1 by a proteasome dependent mechanism. Selectively targeting this collagen fragment, reduced nuclear YAP levels, and enhanced PKA and proteasome activity, while also exhibiting significant antitumor activity in vivo. The present findings not only provided new mechanistic insight into a previously unknown autocrine­like signaling pathway that may provide tumor cells with the ability to regulate PD­L1, but our findings may also help in the development of more effective strategies to control pro­tumorigenic ß3­integrin signaling without disrupting its tumor suppressive functions in other cellular compartments.

Management of cardiac toxicity in patients receiving vascular endothelial growth factor signaling pathway inhibitors.

BACKGROUND: Interfering with angiogenesis is an effective, widely used approach to cancer therapy, but antiangiogenic therapies have been associated with important systemic cardiovascular toxicities such as hypertension, left ventricular dysfunction, heart failure, and myocardial ischemia and infarction. As the use of vascular endothelial growth factor signaling pathway (VSP) inhibitors broadens to include older patients and those with existing cardiovascular disease, the adverse effects are likely to be more frequent, and cardiologists will increasingly be enlisted to help oncologists manage patients who develop adverse cardiovascular effects. METHODS: The Cardiovascular Toxicities Panel of the National Cancer Institute reviewed the published literature and abstracts from major meetings, shared experience gained during clinical development of VSP inhibitors, and contributed extensive clinical experience in evaluating and treating patients with cancer with cardiovascular disease. This report was edited and approved by the National Cancer Institute Investigational Drug Steering Committee. It presents the panel's expert opinion on the current clinical use and future investigation for safer, more expansive use of these drugs. RESULTS AND CONCLUSIONS: The panel recommends that physicians (1) conduct and document a formal risk assessment for existing cardiovascular disease and potential cardiovascular complications before VSP inhibitor treatment recognizing that preexisting hypertension and cardiovascular disease are common in patients with cancer, (2) actively monitor for blood pressure elevations and cardiac toxicity with more frequent assessments during the first treatment cycle, and (3) aggressively manage blood pressure elevations and early symptoms and signs of cardiac toxicity to prevent clinically limiting complications of VSP inhibitor therapy.

Rituximab plus concurrent infusional EPOCH chemotherapy is highly effective in HIV-associated B-cell non-Hodgkin lymphoma.

Rituximab plus intravenous bolus chemotherapy is a standard treatment for immunocompetent patients with B-cell non-Hodgkin lymphoma (NHL). Some studies have suggested that rituximab is associated with excessive toxicity in HIV-associated NHL, and that infusional chemotherapy may be more effective. We performed a randomized phase 2 trial of rituximab (375 mg/m(2)) given either concurrently before each infusional etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone (EPOCH) chemotherapy cycle or sequentially (weekly for 6 weeks) after completion of all chemotherapy in HIV-associated NHL. EPOCH consisted of a 96-hour intravenous infusion of etoposide, doxorubicin, and vincristine plus oral prednisone followed by intravenous bolus cyclophosphamide given every 21 days for 4 to 6 cycles. In the concurrent arm, 35 of 48 evaluable patients (73%; 95% confidence interval, 58%-85%) had a complete response. In the sequential arm, 29 of 53 evaluable patients (55%; 95% confidence interval, 41%-68%) had a complete response. The primary efficacy endpoint was met for the concurrent arm only. Toxicity was comparable in the 2 arms, although patients with a baseline CD4 count less than 50/microL had a high infectious death rate in the concurrent arm. We conclude that concurrent rituximab plus infusional EPOCH is an effective regimen for HIV-associated lymphoma.

Factors influencing adherence to mammography screening guidelines in Appalachian women participating in a mobile mammography program.

The objectives of this study were to evaluate the characteristics (demographic, access to care, health-related behavioral, self and family medical history, psychosocial) of women age 40 years and above who participated in a mobile mammography screening program conducted throughout West Virginia (WV) to determine the factors influencing their self-reported adherence to mammography screening guidelines. Data were analyzed using the Andersen Behavioral Model of Healthcare Utilization framework to determine the factors associated with adherence to mammography screening guidelines in these women. Of the 686 women included in the analysis, 46.2% reported having had a mammogram in the past 2 years. Bivariate analyses showed predisposing factors such as older age and unemployed status, visit to a obstetrician/gynecologist (OB/GYN) in the past year (an enabling factor) and need-related factors such as having a family history of breast cancer (BC), having had breast problems in the past, having had breast biopsy in the past, having had a Pap test in past 2 years, and having had all the screenings for cholesterol, blood glucose, bone mineral density and high blood pressure in past 2 years to be significant predictors of self-reported adherence to mammography guidelines. In the final model, being above 50 years (OR=2.132), being morbidly obese (OR=2.358), having BC-related events and low knowledge about mammography were significant predictors of self-reported adherence. Breast cancer related events seem to be associated with mammography screening adherence in this rural Appalachian population. Increasing adherence to mammography screening may require targeted, community-based educational interventions that precede and complement visits by the mobile mammography unit.

A phase I study of rebeccamycin analog in combination with oxaliplatin in patients with refractory solid tumors.

Rebeccamycin analog (RA) is an antitumor antibiotic with both topoisomerase I and II inhibiting activity. Topoisomerase inhibitors have demonstrated synergy with platinum agents. We performed a phase I trial of combination RA with oxaliplatin in patients with refractory solid tumors. RA was administered as a 1-hour infusion daily on days 1-5 with oxaliplatin administered on day 5. Cycles were repeated every 21 days. A total of 17 patients were enrolled. The MTD for RA was 80 mg/m(2)/d for five days along with oxaliplatin 130 mg/m(2) on day 5. Myelosuppression was a common occurrence but was mild except in one instance. Dose limiting toxicities included atrial fibrillation and hypophosphatemia. There was evidence of antitumor activity including 3 partial responses in patients with esophageal, gallbladder and hepato-cellular carcinoma; 5 additional patients had stable disease. Thus, the combination of RA and oxaliplatin is both tolerable and has evidence of clinical activity, but given the lack of significant activity for single agent RA across a variety of disease sites, it is unlikely to proceed to phase II development.

Higher busulfan dose intensity does not improve outcomes of patients undergoing allogeneic haematopoietic cell transplantation following fludarabine, busulfan-based reduced toxicity conditioning.

We evaluated the impact of busulfan dose intensity in patients undergoing reduced toxicity/intensity conditioning allogeneic transplantation in a multicenter retrospective study of 112 consecutive patients. Seventy-five patients were conditioned with busulfan (0.8 mg/kg/dose IV × 8 doses), fludarabine (30 mg/m(2) /day, days -7 to -3), and 6 mg/kg of ATG [reduced intensity conditioning (RIC) group], while 37 patients received a more-intense conditioning with busulfan (130 mg/m(2) /day IV, days -6 to -3), fludarabine (40 mg/m(2) /day, days -6 to -3) and 6 mg/kg of ATG [reduced toxicity conditioning (RTC) group]. At baseline both groups were matched for median age, unrelated donor allografts, and human leukocyte antigen-mismatched allografts. More patients in RIC group had high-risk disease, and higher median comorbidity index. There were no graft rejections. Median time to neutrophil (17 days vs. 15 days; p = 0.003) and platelet engraftment (16 days vs. 11 days; p < 0.001) was significantly longer in the RIC group. RTC group had significantly more bacterial (62.2% vs. 32%; p = 0.004) and fungal infections (13.5% vs. 1.3% p = 0.01). For RIC and RTC groups rates of grades II-IV acute GVHD (34% vs. 40%; p-value = 0.54), and chronic GVHD (45% vs. 57%; p-value = 0.30) were not significantly different. In similar order at 1 year the cumulative-incidence of non-relapse mortality (NRM; 12% vs. 21%; p-value = 0.21) and relapse rates (38% vs. 39%; p = 0.96) were not significantly different. Patients in RIC and RTC groups had similar 1-year overall survival (61% vs. 50%, p = 0.11) and progression-free survival (50% vs. 36%, p-value = 0.39). Our data suggest that the merits of higher busulfan dose intensity in the context of fludarabine/busulfan-based RTC may be offset by higher early morbidity.

The importance of clinical grading of heart failure and other cardiac toxicities during chemotherapy: updating the common terminology criteria for clinical trial reporting.

Although the use of chemotherapy and targeted therapy has improved the clinical benefit, progression-free survival, and overall survival of various cancers in recent years, old and new toxicities have limited their use. To balance the risk with the benefit of treatment, Common Toxicity Criteria and now Common Terminology Criteria for Adverse Events (CTCAE) have been used by the oncology community for more than 20 years to assess toxicity from cancer treatment. This article details the description and grading of cardiac toxicities reported in association with cancer treatment and the use of CTCAE to assess them.

Ocular surface squamous neoplasia in patients with HIV infection in sub-Saharan Africa.

PURPOSE OF REVIEW: Ocular surface squamous neoplasia (OSSN) in sub-Saharan countries is an aggressive tumor that affects younger patients and appears to be increasing in incidence. There are data to suggest the association of this disease with solar radiation exposure, HIV, and human papilloma virus (HPV). This trend possibly reflects the association of the high incidence of HIV, concomitant high incidence of exposure to HPV, and the solar radiation exposure that people in this region of the world receive. We undertook a PubMed search with the terms 'ocular surface squamous neoplasia', 'conjunctival carcinoma', 'HIV' and 'HPV', and 'sub-Saharan/Africa' to ascertain the scope of the problem and to review the available data, with an emphasis on publications of 2009 and the first quarter of 2010. RECENT FINDINGS: There is increasing evidence of a significant association between HIV seropositivity and OSSN. The role of HPV as contributing to the cause of OSSN is being investigated. SUMMARY: Patients with conjunctival cancer in sub-Saharan Africa are typically younger and more than 50% have underlying HIV infection. Initial presentation can be asymptomatic; however, many of these patients have advanced disease before they seek medical help and OSSN appears to have a more aggressive clinical course in sub-Saharan Africa. Treatment in Africa is primarily surgical. Chemotherapy and antiviral agents have been used. A diagnosis of OSSN in younger patients in sub-Saharan Africa should prompt HIV serotesting.

A vasculature-targeting regimen of preoperative docetaxel with or without bevacizumab for locally advanced breast cancer: impact on angiogenic biomarkers.

PURPOSE: Taxanes have effects on angiogenesis causing difficulties in separating biological effects of chemotherapy from those due to angiogenesis inhibitors. This randomized phase II trial was designed to evaluate the additional biomarker effect on angiogenesis when bevacizumab is added to docetaxel. EXPERIMENTAL DESIGN: Patients with inoperable breast cancer were randomized to either 2 cycles of preoperative docetaxel (D) 35 mg/m(2) i.v. weekly for 6 weeks, followed by a 2-week break; or docetaxel with bevacizumab 10 mg/kg i.v. every other week for a total of 16 weeks (DB). Plasma and serum markers of endothelial damage, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and tumor microvessel density were assessed before treatment and at the end of each preoperative cycle. RESULTS: Forty-nine patients were randomized (DB, 24; D, 25). There was no difference in overall clinical response, progression-free survival, or overall survival. Vascular endothelial growth factor increased during treatment; more so with DB (P < 0.0001). Vascular cell adhesion molecule-1 (VCAM-1) also increased (P < 0.0001); more so with DB (P = 0.069). Intercellular adhesion molecule increased (P = 0.018) and E-selectin decreased (P = 0.006) overall. Baseline levels of VCAM-1 and E-selectin correlated with clinical response by univariate analysis. DCE-MRI showed a greater decrease in tumor perfusion calculated by initial area under the curve for the first 90 seconds in DB (P = 0.024). DCE-MRI also showed an overall decrease in tumor volume (P = 0.012). CONCLUSION: Bevacizumab plus docetaxel caused a greater increase in vascular endothelial growth factor and VCAM-1, and a greater reduction in tumor perfusion by DCE-MRI compared with docetaxel. Clinical outcomes of inoperable breast cancer were predicted by changes in VCAM-1 and E-selectin.