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U.S. forests, particularly in the eastern states, provide an important offset to greenhouse gas (GHG) emissions. Some have proposed that forest‐based natural climate solutions can be strengthened via a number of strategies, including increases in the production of forest biomass energy. We used output from a forest dynamics model (SORTIE‐ND) in combination with a GHG accounting tool (ForGATE) to estimate the carbon consequences of current and intensified timber harvest regimes in the Northeastern United States. We considered a range of carbon pools including forest ecosystem pools, forest product pools, and waste pools, along with different scenarios of feedstock production for biomass energy. The business‐as‐usual (BAU) scenario, which represents current harvest practices derived from the analysis of U.S. Forest Service Forest Inventory and Analysis data, sequestered more net CO2 equivalents than any of the intensified harvest and feedstock utilization scenarios over the next decade, the most important time period for combatting climate change. Increasing the intensity of timber harvest increased total emissions and reduced landscape average forest carbon stocks, resulting in reduced net carbon sequestration relative to current harvest regimes. Net carbon sequestration "parity points," where the regional cumulative net carbon sequestration from alternate intensified harvest scenarios converge with and then exceed the BAU baseline, ranged from 12 to 40 years. A "no harvest" scenario provides an estimate of an upper bound on forest carbon sequestration in the region given the expected successional dynamics of the region's forests but ignores leakage. Regional net carbon sequestration is primarily influenced by (1) the harvest regime and amount of forest biomass removal, (2) the degree to which bioenergy displaces fossil fuel use, and (3) the proportion of biomass diverted to energy feedstocks versus wood products. [ABSTRACT FROM AUTHOR]

Forest carbon offset protocols reward measurable carbon stocks to adhere to accepted greenhouse gas (GHG) accounting principles. This focus on measurable stocks threatens permanence and shifts project-level risks from natural disturbances to an offset registry’s buffer pool. This creates bias towards current GHG benefits, where greater but potentially high-risk stocks are incentivized vs. medium-term to long-term benefits of reduced but more stable stocks. We propose a probability-based accounting framework that allows for more complete risk accounting for forest carbon while still adhering to International Organization for Standardization (ISO) GHG accounting principles. We identify structural obstacles to endorsement of probability-based accounting in current carbon offset protocols and demonstrate through a case study how to overcome these obstacles without violating ISO GHG principles. The case study is the use of forest restoration treatments in fire-adapted forests that stabilize forest carbon and potentially avoid future wildfire emissions. Under current carbon offset protocols, these treatments are excluded since carbon stocks are lowered initially. This limitation is not per se required by ISO’s GHG accounting principles. We outline how real, permanent, and verifiable GHG benefits can be accounted for through a probability-based framework that lowers stressors on a registry’s buffer pool. [ABSTRACT FROM AUTHOR]

A mild photocatalytic phenol oxygenation enabled by a continuous‐flow photoreactor using visible light and pressurized air is described herein. Products for wide‐ranging applications, including the synthesis of vitamins, were obtained in high yields by precisely controlling principal process parameters. The reactor design permits low organophotocatalyst loadings to generate singlet oxygen. It is anticipated that the efficient aerobic phenol oxygenation to benzoquinones and p‐quinols contributes to sustainable synthesis. [ABSTRACT FROM AUTHOR]

Accelerated partial breast irradiation (APBI), a radiation technique in which only the tumor bed is treated, has now become an acceptable radiation modality for selected early‐stage breast cancer patients. Compared to conventional whole breast irradiation (WBI), APBI has some benefits with regard to the reduced total irradiated breast volume and the shorter treatment time. The role of APBI, which can be delivered using diverse techniques, has been evaluated in several prospective randomized phase III trials. These clinical trials demonstrate diverging outcomes relating to local recurrence, while establishing comparable effect in terms of survival between APBI with WBI. The aim of this study was to review the current status of APBI with a focus on clinical practice. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common malignancy in women, and most patients will present with early- stage disease. Multiple clinical trials have established the oncologic equivalence of the various treatment options available to these patients; however, each treatment approach is associated with varying degrees of complication rates, costs, and patient satisfaction. Reconciling these factors to formulate the "best" treatment plan for each individual patient can be a challenge. For example, a given intervention may result in high patient satisfaction at the expense of increased cost and complications. Conversely, an intervention with a low cost and low complication rate may result in poor patient satisfaction. Thus, a value-based approach, which aims to offset these often-competing factors, can optimize patient outcomes while reducing overall costs. Ongoing efforts seek to accurately and comprehensively define value for early breast cancer treatment strategies in order to optimize healthcare resource allocation. Population-based studies using registry or private insurance data have shed light on the cost of primary oncologic interventions and secondary costs from managing complications. Patient satisfaction has been assessed with survey data, and continues to be a subject of ongoing investigation. In this article, the authors review some of the salient data that can be used as a starting point for discussing management principles in a way that optimizes value to the benefit of the patient and the larger healthcare system. A path forward that emphasizes leveraging research efforts to define value and engaging patients in value-based treatment decisions is proposed. [ABSTRACT FROM AUTHOR]

Background: Guideline-concordant local therapy options for early breast cancer include lumpectomy plus whole breast irradiation (Lump+WBI), lumpectomy plus brachytherapy, mastectomy alone, mastectomy plus reconstruction, and, in older women, lumpectomy alone. We performed a comparative examination of each treatment's complications and cost to assess their relative values.Methods: Using the MarketScan database of younger women with private insurance and the SEER-Medicare database of older women with public insurance, we identified 105 211 women with early breast cancer diagnosed between 2000 and 2011. We used diagnosis and procedural codes to identify treatment complications within 24 months of diagnosis and compared complications by treatment using two-sided logistic regression. Mean total and complication-related cost, relative to Lump+WBI, were calculated from a payer's perspective and adjusted for differences in covariables using linear regression. All statistical tests were two-sided.Results: Lump+WBI was the most commonly used treatment. Mastectomy plus reconstruction was associated with nearly twice the complication risk of Lump+WBI (Marketscan: 54.3% vs 29.6%, relative risk [RR] = 1.87, 95% confidence interval [CI] = 1.82 to 1.91, P < .001; SEER-Medicare: 66.1% vs 37.6%, RR = 1.75, 95% CI = 1.69 to 1.82, P < .001) and was also associated with higher adjusted total cost (Marketscan: $22 481 greater than Lump+WBI; SEER-Medicare: $1748 greater) and complication-related cost (Marketscan: $9017 greater; SEER-Medicare: $2092 greater). Brachytherapy had modestly higher total cost and complications than WBI. Lumpectomy alone entailed lower cost and complications in the SEER-Medicare cohort only.Conclusions: Mastectomy plus reconstruction results in substantially higher complications and cost than other guideline-concordant treatment options for early breast cancer. These findings are relevant to patients evaluating their local therapy options and to value-based population health management. [ABSTRACT FROM AUTHOR]

Skin sparing mastectomy, a surgical procedure sparing a large portion of the overlying skin of the breast, and nipple-sparing mastectomy, sparing the whole nipple-areolar complex, are increasingly used, although their oncologic efficacy remains unclear. The aim of this study was to assess the radiation oncologists' opinions regarding the indications of radiation therapy ( RT) after skin-sparing mastectomy and nipple-sparing mastectomy. Radiation oncology members of four national and international societies were invited to complete a questionnaire comprising of 22 questions to assess their opinions regarding RT indications in the context of skin-sparing and nipple-sparing mastectomy. A total of 298 radiation oncologists answered the questionnaire. 90.9% of respondents affirmed that breast cancer is one of their specializations. The majority declared that post-mastectomy RT is indicated for early-stage (stages I and II) breast cancer patients who present with risk factors for recurrence after skin-sparing or nipple-sparing mastectomy (87.2% and 80.2%, respectively). All suggested risk factors (tumor size, lymph node involvement, extracapsular extension, lymphovascular space invasion, positive surgical margins, triple negative tumor, multicentric tumor, and age) were considered as major elements (important or very important). There is no consensus regarding the necessity of evaluating residual breast tissue or the definition of residual breast tissue after mastectomy. All classic factors were considered as major elements, potentially influencing the decision to advice or not postoperative RT. Many uncertainties remain about the indications for RT after skin-sparing mastectomy or nipple-sparing mastectomy. [ABSTRACT FROM AUTHOR]

Background: Galectin-3 (Gal3) plays diverse roles in cancer initiation, progression, and drug resistance depending on tumor type characteristics that are also associated with cancer stem cells (CSCs). Recurrence of breast carcinomas may be attributed to the presence of breast CSCs (BCSCs). BCSCs exist in mesenchymal-like or epithelial-like states and the transition between these states endows BCSCs with the capacity for tumor progression. The discovery of a feedback loop with galectins during epithelial-to-mesenchymal transition (EMT) prompted us to investigate its role in breast cancer stemness. Method: To elucidate the role of Gal3 in BCSCs, we performed various in vitro and in vivo studies such as sphere-formation assays, Western blotting, flow cytometric apoptosis assays, and limited dilution xenotransplant models. Histological staining for Gal3 in tissue microarrays of breast cancer patients was performed to analyze the relationship of clinical outcome and Gal3 expression. Results: Here, we show in a cohort of 87 node-positive breast cancer patients treated with doxorubicin-based chemotherapy that low Gal3 was associated with increased lymphovascular invasion and reduced overall survival. Analysis of in vitro BCSC models demonstrated that Gal3 knockdown by small hairpin RNA (shRNA) interference in epithelial-like mammary spheres leads to EMT, increased sphere-formation ability, drug-resistance, and heightened negative aldefluor activity. Furthermore, Gal3negative BCSCs were associated with enhanced tumorigenicity in orthotopic mouse models. Conclusions: Thus, in at least some breast cancers, loss of Gal3 might be associated with EMT and cancer stemness-associated traits, predicts poor response to chemotherapy, and poor prognosis. [ABSTRACT FROM AUTHOR]

Background: The authors compared longitudinal patient-reported outcomes and physician-rated cosmesis with conventionally fractionated whole-breast irradiation (CF-WBI) versus hypofractionated whole-breast irradiation (HF-WBI) within the context of a randomized trial.Methods: From 2011 to 2014, a total of 287 women with American Joint Committee on Cancer stage 0 to stage II breast cancer were randomized to receive CF-WBI (at a dose of 50 grays in 25 fractions plus a tumor bed boost) or HF-WBI (at a dose of 42.56 grays in 16 fractions plus a tumor bed boost) after breast-conserving surgery. Patient-reported outcomes were assessed using the Breast Cancer Treatment Outcome Scale (BCTOS), the Functional Assessment of Cancer Therapy-Breast, and the Body Image Scale and were recorded at baseline and 0.5, 1, 2, and 3 years after radiotherapy. Physician-rated cosmesis was assessed at the same time points. Outcomes by treatment arm were compared at each time point using a 2-sided Student t test. Multivariable mixed effects growth curve models assessed the effects of treatment arm and time on longitudinal outcomes.Results: Of the 287 patients enrolled, 149 were randomized to CF-WBI and 138 were randomized to HF-WBI. At 2 years, the Functional Assessment of Cancer Therapy-Breast Trial Outcome Index score was found to be modestly better in the HF-WBI arm (mean 79.6 vs 75.9 for CF-WBI; P = .02). In multivariable mixed effects models, treatment arm was not found to be associated with longitudinal outcomes after adjusting for time and baseline outcome measures (P≥.14). The linear effect of time was significant for BCTOS measures of functional status (P = .001, improved with time) and breast pain (P = .002, improved with time).Conclusions: In this randomized trial, longitudinal outcomes did not appear to differ by treatment arm. Patient-reported functional and pain outcomes improved over time. These findings are relevant when counseling patients regarding decisions concerning radiotherapy. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2886-2894. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Brain metastasis poses a major treatment challenge and remains an unmet clinical need. Finding novel therapies to prevent and treat brain metastases requires an understanding of the biology and molecular basis of the process, which currently is constrained by a dearth of experimental models and specific therapeutic targets.Methods: Green Fluorescent Protein (GFP)-labeled breast cancer cells were injected via tail vein into SCID/Beige mice (n = 10-15 per group), and metastatic colonization to the brain and lung was evaluated eight weeks later. Knockdown and overexpression of miR-141 were achieved with lentiviral vectors. Serum levels of miR-141 were measured from breast cancer patients (n = 105), and the association with clinical outcome was determined by Kaplan-Meier method. All statistical tests were two-sided.Results: Novel brain metastasis mouse models were developed via tail vein injection of parental triple-negative and human epidermal growth factor receptor 2 (HER2)-overexpressing inflammatory breast cancer lines. Knockdown of miR-141 inhibited metastatic colonization to brain (miR-141 knockdown vs control: SUM149, 0/8 mice vs 6/9 mice,P= .009; MDA-IBC3, 2/14 mice vs 10/15 mice,P= .007). Ectopic expression of miR-141 in nonexpressing MDA-MB-231 enhanced brain metastatic colonization (5/9 mice vs 0/10 mice,P= .02). Furthermore, high miR-141 serum levels were associated with shorter brain metastasis-free survival (P= .04) and were an independent predictor of progression-free survival (hazard ratio [HR] = 4.77, 95% confidence interval [CI] = 2.61 to 8.71,P< .001) and overall survival (HR = 7.22, 95% CI = 3.46 to 15.06,P< .001).Conclusions: Our study suggests miR-141 is a regulator of brain metastasis from breast cancer and should be examined as a biomarker and potential target to prevent and treat brain metastases. [ABSTRACT FROM AUTHOR]

Purpose: Value in healthcare-i.e., patient-centered outcomes achieved per healthcare dollar spent-can define quality and unify performance improvement goals with health outcomes of importance to patients across the entire cycle of care. We describe the process through which value-based measures for breast cancer patients and dynamic capture of these metrics via our new electronic health record (EHR) were developed at our institution. Methods: Contemporary breast cancer literature on treatment options, expected outcomes, and potential complications was extensively reviewed. Patient perspective was obtained via focus groups. Multidisciplinary physician teams met to inform a 3-phase process of (1) concept development, (2) measure specification, and (3) implementation via EHR integration. Results: Outcomes were divided into 3 tiers that reflect the entire cycle of care: (1) health status achieved, (2) process of recovery, and (3) sustainability of health. Within these tiers, 22 patient-centered outcomes were defined with inclusion/exclusion criteria and specifications for reporting. Patient data sources will include the Epic Systems EHR and validated patient-reported outcome questionnaires administered via our institution's patient portal. Conclusions: As healthcare costs continue to rise in the United States and around the world, a value-based approach with explicit, transparently reported patient outcomes will not only create opportunities for performance improvement but will also enable benchmarking across providers, healthcare systems, and even countries. Similar value-based breast cancer care frameworks are also being pursued internationally. [ABSTRACT FROM AUTHOR]

Although forest biomass energy was long assumed to be carbon neutral, many studies show delays between forest biomass carbon emissions and sequestration, with biomass carbon causing climate change damage in the interim. While some models suggest that these primary biomass carbon effects may be mitigated by induced market effects, for example, from landowner decisions to increase afforestation due to higher biomass prices, the delayed carbon sequestration of biomass energy systems still creates considerable scientific debate (i.e., how to assess effects) and policy debate (i.e., how to act given these effects). Forests can be carbon sinks, but their carbon absorption capacity is finite. Filling the sink with fossil fuel carbon thus has a cost, and conversely, harvesting a forest for biomass energy - which depletes the carbon sink - creates potential benefits from carbon sequestration. These values of forest carbon sinks have not generally been considered. Using data from the 2010 Manomet Center for Conservation Sciences 'Biomass sustainability and carbon policy study' and a model of forest biomass carbon system dynamics, we investigate how discounting future carbon flows affects the comparison of biomass energy to fossil fuels in Massachusetts, USA. Drawing from established financial valuation metrics, we calculate internal rates of return ( IRR) as explicit estimates of the temporal values of forest biomass carbon emissions. Comparing these IRR to typical private discount rates, we find forest biomass energy to be preferred to fossil fuel energy in some applications. We discuss possible rationales for zero and near-zero social discount rates with respect to carbon emissions, showing that social discount rates depend in part on expectations about how climate change affects future economic growth. With near-zero discount rates, forest biomass energy is preferred to fossil fuels in all applications studied. Higher IRR biomass energy uses (e.g., thermal applications) are preferred to lower IRR uses (e.g., electricity generation without heat recovery). [ABSTRACT FROM AUTHOR]

Background: It is currently unclear whether the superior normal organ-sparing effect of intensity-modulated radiotherapy (IMRT) compared with 3-dimensional radiotherapy (3D) has a clinical impact on survival and cardiopulmonary mortality in patients with esophageal cancer (EC).Methods: The authors identified 2553 patients aged > 65 years from the Surveillance, Epidemiology, and End Results (SEER)-Medicare and Texas Cancer Registry-Medicare databases who had nonmetastatic EC diagnosed between 2002 and 2009 and were treated with either 3D (2240 patients) or IMRT (313 patients) within 6 months of diagnosis. The outcomes of the 2 cohorts were compared using inverse probability of treatment weighting adjustment.Results: Except for marital status, year of diagnosis, and SEER region, both radiation cohorts were well balanced with regard to various patient, tumor, and treatment characteristics, including the use of IMRT versus 3D in urban/metropolitan or rural areas. IMRT use increased from 2.6% in 2002 to 30% in 2009, whereas the use of 3D decreased from 97.4% in 2002 to 70% in 2009. On propensity score inverse probability of treatment weighting-adjusted multivariate analysis, IMRT was not found to be associated with EC-specific mortality (hazard ratio [HR], 0.93; 95% confidence interval [95% CI], 0.80-1.10) or pulmonary mortality (HR, 1.11; 95% CI, 0.37-3.36), but was significantly associated with lower all-cause mortality (HR, 0.83; 95% CI, 0.72-0.95), cardiac mortality (HR, 0.18; 95% CI, 0.06-0.54), and other-cause mortality (HR, 0.54; 95% CI, 0.35-0.84). Similar associations were noted after adjusting for the type of chemotherapy, physician experience, and sensitivity analysis removing hybrid radiation claims.Conclusions: In this population-based analysis, the use of IMRT was found to be significantly associated with lower all-cause mortality, cardiac mortality, and other-cause mortality in patients with EC. [ABSTRACT FROM AUTHOR]

The potential greenhouse gas benefits of displacing fossil energy with biofuels are driving policy development in the absence of complete information. The potential carbon neutrality of forest biomass is a source of considerable scientific debate because of the complexity of dynamic forest ecosystems, varied feedstock types, and multiple energy production pathways. The lack of scientific consensus leaves decision makers struggling with contradicting technical advice. Analyzing previously published studies, our goal was to identify and prioritize those attributes of bioenergy greenhouse gas (GHG) emissions analysis that are most influential on length of carbon payback period. We investigated outcomes of 59 previously published forest biomass greenhouse gas emissions research studies published between 1991 and 2014. We identified attributes for each study and classified study cases by attributes. Using classification and regression tree analysis, we identified those attributes that are strong predictors of carbon payback period (e.g. the time required by the forest to recover through sequestration the carbon dioxide from biomass combusted for energy). The inclusion of wildfire dynamics proved to be the most influential in determining carbon payback period length compared to other factors such as feedstock type, baseline choice, and the incorporation of leakage calculations. Additionally, we demonstrate that evaluation criteria consistency is required to facilitate equitable comparison between projects. For carbon payback period calculations to provide operational insights to decision makers, future research should focus on creating common accounting principles for the most influential factors including temporal scale, natural disturbances, system boundaries, GHG emission metrics, and baselines. [ABSTRACT FROM AUTHOR]

Background: This study sought to determine outcomes for patients with metastatic breast cancer (MBC) with no evidence of disease (NED) after treatment and to identify factors predictive of outcomes once the status of NED was attained.Methods: This study reviewed 570 patients with MBC who were consecutively treated between January 2003 and December 2005. Ninety patients (16%) attained NED, which was defined as a complete metabolic response on positron emission tomography or sclerotic healing of bone metastases on computed tomography or magnetic resonance imaging. The median follow-up for patients attaining NED was 100 months (range, 14-134 months).Results: The 3- and 5-year overall survival (OS) rates were 44% and 24%, respectively, for the entire group and 96% and 78%, respectively, for those attaining NED. According to a landmark analysis, NED status was significantly associated with survival at 2 (P < .001; hazard ratio [HR], 0.23; 95% confidence interval [CI], 0.16-0.34) and 3 years (P < .001; HR, 0.20; 95% CI, 0.14-0.30). From the time of NED, the median survival was 102 months (range, 14-134 months) with 5-year OS and progression-free survival (PFS) rates of 77% and 40%, respectively. According to a multivariate analysis, human epidermal growth factor receptor 2 positivity was significantly associated with OS in comparison with estrogen receptor positivity (P = .02; HR, 0.44; 95% CI, 0.21-0.90), and trastuzumab use was significantly associated with PFS (P = .007; HR, 0.48; 95% CI, 0.28-0.82). Thirty-one patients (34%) with NED remained in remission at the last follow-up.Conclusions: MBC patients who attain the status of NED have significantly prolonged survival with a durable response to therapy. Ultimately, this study provides essential outcome data for clinicians and patients living with MBC. [ABSTRACT FROM AUTHOR]

The article examines the effectiveness of postmastectomy radiotherapy (PMRT) in patients with locally advanced breast. An overview on the multiple randomized trials concerning the benefits of PMRT, is provided. Also investigated is the meta-analysis on the role of PMRT in the development of early-stage disease.

Inflammatory breast cancer (IBC) is a rare and aggressive disease. Previous studies have shown that among patients with stage III breast cancer, IBC is associated with a worse prognosis than noninflammatory breast cancer (non-IBC). Whether this difference holds true among patients with stage IV breast cancer has not been studied. We tested the hypothesis that overall survival (OS) is worse in patients with IBC than in those with non-IBC among patients with distant metastasis at diagnosis (stage IV disease). We reviewed the records of 1504 consecutive patients with stage IV breast cancer (IBC: 206; non-IBC: 1298) treated at our institution from 1987 through 2012. Survival curves for IBC and non-IBC subcohorts were compared. The Cox proportional hazards model was used to determine predictors of OS. The median follow-up period was 4.7 years. IBC was associated with shorter median OS time than non-IBC (2.27 vs. 3.40 years; P = 0.0128, log-rank test). In a multicovariate Cox model that included 1389 patients, the diagnosis of IBC was a significant independent predictor of worse OS (hazard ratio = 1.431, P = 0.0011). Other significant predictors of worse OS included Black (vs. White) ethnicity, younger age at diagnosis, negative HER2 status, and visceral (vs. nonvisceral) site of metastasis. IBC is associated with shorter OS than non-IBC in patients with distant metastasis at diagnosis. The prognostic impact of IBC should be taken into consideration among patients with stage IV breast cancer. [ABSTRACT FROM AUTHOR]

Neoadjuvant chemotherapy is a standard treatment option for patients with locally advanced operable breast cancer and is increasingly used in early breast cancer. Initial randomized trials of neoadjuvant chemotherapy established equivalency to adjuvant chemotherapy in terms of survival, but they also demonstrated improved rates of breast conservation and the ability to modify the risk of locoregional recurrence after a favorable response to chemotherapy. High-quality nonrandomized data have helped to tailor radiotherapy treatment recommendations after neoadjuvant chemotherapy and breast-conserving surgery or mastectomy. Results from an ongoing phase 3 randomized trial (NSABP B-51/RTOG 1304) will help to clarify the value of locoregional radiotherapy for patients with clinical N1 disease that becomes node negative after neoadjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Introduction: Inflammatory breast cancer (IBC) is an aggressive type of breast cancer, characterized by very rapid progression, enlargement of the breast, skin edema causing an orange peel appearance (peau d'orange), erythema, thickening, and dermal lymphatic invasion. It is characterized by E-cadherin overexpression in the primary and metastatic disease, but to date no robust molecular features that specifically identify IBC have been reported. Further, models that recapitulate all of these clinical findings are limited and as a result no studies have demonstrated modulation of these clinical features as opposed to simply tumor cell growth. Methods: Hypothesizing the clinical presentation of IBC may be mediated in part by the microenvironment, we examined the effect of co-injection of IBC xenografts with mesenchymal stem/stromal cells (MSCs). Results: MSCs co-injection significantly increased the clinical features of skin invasion and metastasis in the SUM149 xenograft model. Primary tumors co-injected with MSCs expressed higher phospho-epidermal growth factor receptor (p-EGFR) and promoted metastasis development after tumor resection, effects that were abrogated by treatment with the epidermal growth factor receptor (EGFR) inhibitor, erlotinib. E-cadherin expression was maintained in primary tumor xenografts with MSCs co-injection compared to control and erlotinib treatment dramatically decreased this expression in control and MSCs co-injected tumors. Tumor samples from patients demonstrate correlation between stromal and tumor p-EGFR staining only in IBC tumors. Conclusions: Our findings demonstrate that the IBC clinical phenotype is promoted by signaling from the microenvironment perhaps in addition to tumor cell drivers. [ABSTRACT FROM AUTHOR]

Interaction between the epidermal growth factor receptor ( EGFR) and the insulin-like growth factor receptor ( IGF-1R) has been well established in many cancer types. We investigated the effects of cetuximab ( EGFR antibody) and IMC-A12 ( IGF-1R antibody) on the response of head and neck squamous cell carcinoma ( HNSCC) to radiation therapy ( RT). The effects of cetuximab and IMC-A12 on cell viability and radiosensitivity were determined by clonogenic cell survival assay. Formation of nuclear γ-H2 AX and 53 BP1 foci was monitored by immunofluorescence. Alterations in target signaling were analyzed by Western blots. In vivo tumor growth delay assay was performed to determine the efficacy of triple therapy with IMC-A12, cetuximab, and RT. In vitro data showed that cetuximab differentially affected the survival and the radiosensitivity of HNSCC cells. Cetuximab suppressed DNA repair that was evident by the prolonged presence of nuclear γ-H2 AX and 53 BP1 foci. IMC-A12 did not have any effect on the cell survival. However, it increased the radiosensitivity of one of the cell lines. EGFR inhibition increased IGF-1R expression levels and also the association between EGFR and IGF-1R. Addition of IMC-A12 to cetuximab did not increase the radiosensitivity of these cells. Tumor xenografts exhibited enhanced response to RT in the presence of either cetuximab or IMC-A12. Concurrent treatment regimen failed to further enhance the tumor response to cetuximab and/or RT. Taken together our data suggest that concomitant inhibition of both EGFR and IGF-1R pathways did not yield additional therapeutic benefit in overcoming resistance to RT. [ABSTRACT FROM AUTHOR]

Objective: We sought to compare hospi utilization for American Indian and Wh Medicare beneficiaries dying of cancer. Methods: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases to analyze claims for 181,316 White and 690 American Indian patients dying of breast, cervix, colorectal, kidney, lung, pancreas, prostate cancer, or stomach cancer from 2003 to 2009. Results: A lower proportion of American Indians enrolled in hospice compared to White patients (54% vs 65%, respectively; P<.0001). While the proportion of White patients who used hospice services in the last 6 months of life increased from 61 % in 2003 to 68% in 2009 (PC.0001), the proportion of American Indian patients using hospice care remained unchanged (P=.57) and remained below that of their White counterparts throughout the years of study. Conclusion: Continued efforts should be made to improve access to culturally relevant hospice care for American Indian patients with terminal cancer. [ABSTRACT FROM AUTHOR]