Traveling to Receive Treatment for Extremity Soft Tissue Sarcomas: Is it worth the drive?

BACKGROUND: Regionalization of sarcoma care may improve outcomes. Concerns exist regarding the burdens of travel and its effects on care. We evaluate the presence of a "distance bias". METHODS: Retrospective cohort study of patients with extremity soft tissue sarcoma (stage I-III) within the NCDB. Travel distance (TD) and hospital volume (VOL) were categorized into quartiles. Alternating statistical models were used for analysis. RESULTS: 1,035 hospitals contributed 11,979 cases. Median and maximum VOL were 5 and 45 cases/year. VOL quartiles were "low-volume" (LV) (892 hospitals, < 3 cases/yr.), "intermediate low-volume" (ILV) (89, 3-5 cases/yr.), "intermediate high-volume" (IHV) (39, 6-12 cases/yr.), and "high-volume" (HV) (15, > 12 cases/yr.). TD quartiles: "short-travel" (ST) (< 8 mi), "intermediate-short travel" (IST) (8-17), "intermediate long-travel" (ILT) (18-49), and "long-travel" (LT) (> 50). VOL but not TD is associated with improved survival [HR 0.65 (CI 0.52-0.83)] and rate of R0 resection [1.87 (CI 1.4-2.5)] but has no effect on amputation rates. Matched analyses demonstrate similar results. CONCLUSIONS: Hospital volume but not distance traveled to treatment facility is associated with improved survival and R0 resections for extremity soft tissue sarcomas. Despite the inconveniences of travel, patients may benefit from treatment at high volume centers.

Upfront resection versus neoadjuvant therapy for T1/T2 pancreatic cancer.

BACKGROUND: The role of neoadjuvant therapy remains controversial for resectable pancreatic neoplasms. We evaluated treatment outcomes for T1/T2 tumors. METHODS: Retrospective study of patients with T1/T2 (Stage I-II) pancreatic cancer within the NCDB. Treatment-sequence variables were used for classification: "surgery + chemotherapy" (S+C), "chemotherapy + surgery" (C+S), "surgery only" (SO), and "chemotherapy only" (CO). RESULTS: 13 412 patients were included; the majority had T2 tumors. 8 490 received upfront surgery; 4 922 preoperative chemotherapy. In the surgery branch, 5 684 received surgery and chemotherapy (S+C); 2 806 did not receive chemotherapy (SO). Of those intended to receive preoperative chemotherapy, 3 804 received only chemotherapy (CO); 1 118 proceeded to surgery (C+S). Median survival for S+C and C+S groups was similar (25.9 vs 26.2) [HR 0.92, p= 0.41]. Compared to the CO group, the SO group had improved median survival (13.5 vs. 10.8) [HR 0.63, p<0.001]. Branched analyses demonstrated improved median and 5-year (20.8% vs 12.7%) survival for patients receiving upfront resection [HR 0.77, p<0.001]. CONCLUSION: Patients with T1/T2 pancreatic cancer have similar survival irrespective of the timing of chemotherapy and surgery, if they receive both. Upfront resection ensures surgery is delivered, increasing the possibility of long-term survival.

Better Defining the Role of Total Neoadjuvant Radiation: Changing Paradigms in Locally Advanced Pancreatic Cancer.

BACKGROUND: This study was designed to better define the role of radiation (Neo-Rad) in addition to neoadjuvant multiagent chemotherapy (NAT) for the treatment of locally advanced pancreatic cancer. METHODS: Retrospective cohort study using the NCDB. Individuals with AJCC clinical T3/T4 pancreatic carcinoma who underwent resection and multiagent chemotherapy were included. Kaplan-Meier, logistic-regression, and Cox proportional-hazard models were used for analysis. RESULTS: A total of 2703 patients were included; 2039 had T3 and 664 had T4 tumors, and 1092 (40.4%) received Neo-Rad. Median follow-up was 22.5 months. During the study period, there was increased use of NAT and a decline in the use of Neo-Rad. Addition of Neo-Rad did not affect 30-day (2.51% vs. 3.24%, p = 0.272) or 90-day mortality (5.23% vs. 6.38%, p = 0.216). Neo-Rad was not associated with improved overall survival on univariable (25.95 vs. 24.7 months, p = 0.202), or multivariable analyses (hazard ratio [HR] 0.94; 95% confidence interval [CI] 0.85-1.05). Time from diagnosis to definitive surgery was increased by Neo-Rad (204 vs. 115 days, p < 0.001). Neo-Rad was associated with increased pathologic downstaging in T3 (32.8% vs. 14.4%) (odds ratio [OR] 2.90; 95% CI 2.30-3.66) and T4 tumors (88.9% vs. 77.8%) (OR 2.29; 95% CI 1.44-3.67); complete pathologic response (5.3% vs. 1.6%) (OR 2.89; 95% CI 1.73-4.83), and increased R0 resection rates (85.7% vs. 76.8%) (OR 1.79; 95% CI 1.44-2.23). CONCLUSIONS: The use of neoadjuvant therapy is increasing for the treatment of locally advanced pancreatic cancer. The addition of radiation to neoadjuvant chemotherapy is associated with improved antineoplastic effectiveness (downstaging, complete pathologic response), surgical resection (R0 rates), but has no effect on overall survival.

A simple matrix to predict treatment success and long-term survival among patients undergoing pancreatectomy.

BACKGROUND: A more accurate measure of long-term survival among patients who have undergone a successful resection for pancreatic adenocarcinoma may be computed by accounting for time already survived during the initial treatment window. METHODS: Patients diagnosed with pancreatic adenocarcinoma, from 2004 through 2013, were identified from the American College of Surgeons National Cancer Database (NCDB). A risk-stratification matrix was constructed including age, histopathologic factors and the use of adjuvant therapy, given successful treatment and survival at 3-month following diagnosis. RESULTS: A total of 25,897 patients (50% male, 53% >65 years of age) presented with stage I-III pancreatic cancer. The majority of patients had tumors >2 cm size (82%), grade I/II (65%), lymphatic invasion (LI) (66%), and negative margins (76%). A survival advantage for adjuvant therapy was observed among all patients, independent of their risk-profile. For example, a patient ≤65 years of age, with early stage cancer (size ≤2 cm, grade I/II, -ve LI, -ve margins) who received adjuvant therapy had a 62% probability of being alive beyond three years (95%CI = 59%-66%). In contrast, the survival probability decreased to 53% (95%CI = 59%-66%) without adjuvant therapy. CONCLUSIONS: These results provide surgeons and patients with more accurate information regarding long-term survival, as well as the benefit of opting for adjuvant therapy after successful pancreatic surgery.

Procedure-based postoperative risk prediction using NSQIP data.

BACKGROUND: The National Surgical Quality Improvement Program (NSQIP) has proposed using procedure-based hierarchical models to predict adverse outcomes, but it is not clear whether this approach was used to develop the NSQIP "Surgical Risk Calculator". We therefore wished to demonstrate how procedure-based hierarchical models can be constructed and to describe their results. METHODS: NSQIP data from 2015 were used to construct statistical models predicting 30-day postoperative mortality and morbidity, using two-level logistic regression with preoperative patient-level variables as fixed effects and procedure-specific codes as a random intercept. Model performance was validated using NSQIP data from 2014. RESULTS: NSQIP for 2015 contained records for 885,502 patients, of whom 8986 died (1.0%) and 104,836 suffered a complication (11.8%). Complete model specifications and results are presented, including odds ratios for patient-level variable effects and random procedure effects. Most comorbidities were associated with increased morbidity and mortality, but overweight and obesity were associated with lower risk. Odds ratios for individual procedures ranged from 0.117 to 10.85 for mortality and from 0.615 to 8.09 for morbidity. Validation C-statistics were 0.940 for the mortality model and 0.833 for the morbidity model; Brier Scores were 0.0086 and 0.085, respectively. Graphs for 20 quantiles showed good conformity of observed and predicted risk. CONCLUSIONS: Procedure-based hierarchical logistic regression models of NSQIP outcomes had satisfactory overall performance statistics. Model specifications and results are provided for criticism and improvement, and several possible refinements are suggested.

Roles of NGAL and MMP-9 in the tumor microenvironment and sensitivity to targeted therapy.

Various, diverse molecules contribute to the tumor microenvironment and influence invasion and metastasis. In this review, the roles of neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9) in the tumor microenvironment and sensitivity to therapy will be discussed. The lipocalin family of proteins has many important functions. For example when NGAL forms a complex with MMP-9 it increases its stability which is important in cancer metastasis. Small hydrophobic molecules are bound by NGAL which can alter their entry into and efflux from cells. Iron transport and storage are also influenced by NGAL activity. Regulation of iron levels is important for survival in the tumor microenvironment as well as metastasis. Innate immunity is also regulated by NGAL as it can have bacteriostatic properties. NGAL and MMP-9 expression may also affect the sensitivity of cancer cells to chemotherapy as well as targeted therapy. Thus NGAL and MMP-9 play important roles in key processes involved in metastasis as well as response to therapy. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza.

Effects of mutations in Wnt/ß-catenin, hedgehog, Notch and PI3K pathways on GSK-3 activity-Diverse effects on cell growth, metabolism and cancer.

Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase that participates in an array of critical cellular processes. GSK-3 was first characterized as an enzyme that phosphorylated and inactivated glycogen synthase. However, subsequent studies have revealed that this moon-lighting protein is involved in numerous signaling pathways that regulate not only metabolism but also have roles in: apoptosis, cell cycle progression, cell renewal, differentiation, embryogenesis, migration, regulation of gene transcription, stem cell biology and survival. In this review, we will discuss the roles that GSK-3 plays in various diseases as well as how this pivotal kinase interacts with multiple signaling pathways such as: PI3K/PTEN/Akt/mTOR, Ras/Raf/MEK/ERK, Wnt/beta-catenin, hedgehog, Notch and TP53. Mutations that occur in these and other pathways can alter the effects that natural GSK-3 activity has on regulating these signaling circuits that can lead to cancer as well as other diseases. The novel roles that microRNAs play in regulation of the effects of GSK-3 will also be evaluated. Targeting GSK-3 and these other pathways may improve therapy and overcome therapeutic resistance.

Perioperative chemotherapy versus postoperative chemoradiotherapy in patients with resectable gastric/gastroesophageal junction adenocarcinomas: A survival analysis of 5058 patients.

BACKGROUND: Both perioperative chemotherapy (PECT) and postoperative chemoradiotherapy (POCRT) have a significant survival advantage over surgery alone for the treatment of patients with gastric cancer. However, to the best of our knowledge, these regimens have not been compared in a randomized clinical trial. The purpose of the current observational study was to compare overall survival among patients receiving PECT versus POCRT for the treatment of gastric/gastroesophageal junction (GEJ) adenocarcinomas. METHODS: Patients with resected clinical American Joint Committee on Cancer TNM stage II or III adenocarcinomas of the stomach or GEJ from 2004 through 2013 were identified utilizing the National Cancer Data Base. Hazard ratios (HRs), 95% confidence intervals, and P values were computed using a Cox proportional hazards procedure. Multivariable models were adjusted for treatment regimen, age, race, ethnicity, tumor size, TNM stage, Charlson comorbidity index, and tumor grade. RESULTS: Patients receiving PECT had a 72% survival advantage compared with those treated with POCRT (5058 patients; HR, 0.58 [adjusted P<.0001]). The 5-year actuarial survival rate for PECT was 44% compared with 38% for POCRT. A statistically significant survival advantage for PECT also was observed when the analysis was stratified by clinical stage of disease (stage II [3192 patients]: adjusted HR, 0.79 [P = .041]; and stage III [1866 patients]: adjusted HR, 0.49 [P<.0001]). This benefit was greatest among patients with lymph node-positive disease who converted to lymph node-negative status with PECT. CONCLUSIONS: In this large series of patients with stage II/III resected gastric/GEJ adenocarcinomas from >1500 American College of Surgeons Commission on Cancer-accredited facilities, patients receiving PECT were shown to survive longer than those receiving POCRT. Cancer 2017;123:2909-17. © 2017 American Cancer Society.

The defence-associated transcriptome of hexaploid wheat displays homoeolog expression and induction bias.

Bread wheat (Triticum aestivum L.) is an allopolyploid species containing three ancestral genomes. Therefore, three homoeologous copies exist for the majority of genes in the wheat genome. Whether different homoeologs are differentially expressed (homoeolog expression bias) in response to biotic and abiotic stresses is poorly understood. In this study, we applied a RNA-seq approach to analyse homoeolog-specific global gene expression patterns in wheat during infection by the fungal pathogen Fusarium pseudograminearum, which causes crown rot disease in cereals. To ensure specific detection of homoeologs, we first optimized read alignment methods and validated the results experimentally on genes with known patterns of subgenome-specific expression. Our global analysis identified widespread patterns of differential expression among homoeologs, indicating homoeolog expression bias underpins a large proportion of the wheat transcriptome. In particular, genes differentially expressed in response to Fusarium infection were found to be disproportionately contributed from B and D subgenomes. In addition, we found differences in the degree of responsiveness to pathogen infection among homoeologous genes with B and D homoeologs exhibiting stronger responses to pathogen infection than A genome copies. We call this latter phenomenon as 'homoeolog induction bias'. Understanding how homoeolog expression and induction biases operate may assist the improvement of biotic stress tolerance in wheat and other polyploid crop species.

Population-Based Analysis of Completion Lymphadenectomy in Intermediate-Thickness Melanoma.

BACKGROUND: Multicenter selective lymphadenectomy trial 1 (MSLT-I) defined the prognostic and potential therapeutic values of sentinel lymph node biopsy (SLNB) for intermediate-thickness melanoma. The role of completion lymphadenectomy (CLND) is, however, unclear and the subject of the ongoing MSLT-II trial. METHODS: From 2003 to 2012, patients with tumors 1-4 mm thick with positive SLNB were identified in the Surveillance Epidemiology and End Results Program registry. The patients were divided into two groups: group 1 (CLND) and group 2 (observation). RESULTS: The study enrolled 2172 patients, the majority of whom were white and male with extremity primaries, no ulceration, Clark level 4 invasion, and nodes 2.01-4.0 mm deep. In the univariate analysis, CLND was associated with lower mean age, male gender, primary site, number of positive nodes, and geographic region (p < 0.05). In the multivariate analysis, male gender [odds ratio (OR), 1.27] and geographic area (Michigan OR, 2.31; Iowa OR, 1.69) were associated with CLND (p < 0.05). In the survival analysis, male gender, primary site, ulceration, Clark level, and depth and number of positive nodes were associated with survival (p < 0.05), but CLND was not (p = 0.83). In the Cox regression analysis, the relationship between male gender [hazard ratio (HR), 1.14], primary site trunk versus extremity (HR, 1.3), ulceration (HR, 1.79), Clark level (2 vs. 4 HR, 3.51; 2 vs. 5 HR, 6.48), depth (HR, 1.43) and number of nodes (1 vs. 2: HR, 1.23; 1 vs. ≥3: HR, 2.52) persisted (p < 0.05). However, when CLND was included in this model, it was not associated with improved survival. CONCLUSIONS: Age, gender, and geographic area predict the likelihood of CLND. In this retrospective study, CLND did not add survival benefit.

The Fusarium crown rot pathogen Fusarium pseudograminearum triggers a suite of transcriptional and metabolic changes in bread wheat (Triticum aestivum L.).

Background and Aims: Fusarium crown rot caused by the fungal pathogen Fusarium pseudograminearum is a disease of wheat and barley, bearing significant economic cost. Efforts to develop effective resistance to this disease have been hampered by the quantitative nature of resistance and a lack of understanding of the factors associated with resistance and susceptibility. Here, we aimed to dissect transcriptional responses triggered in wheat by F. pseudograminearum infection. Methods: We used an RNA-seq approach to analyse host responses during a compatible interaction and identified >2700 wheat genes differentially regulated after inoculation with F. pseudograminearum . The production of a few key metabolites and plant hormones in the host during the interaction was also analysed. Key Results: Analysis of gene ontology enrichment showed that a disproportionate number of genes involved in primary and secondary metabolism, signalling and transport were differentially expressed in infected seedlings. A number of genes encoding pathogen-responsive uridine-diphosphate glycosyltransferases (UGTs) potentially involved in detoxification of the Fusarium mycotoxin deoxynivalenol (DON) were differentially expressed. Using a F. pseudograminearum DON-non-producing mutant, DON was shown to play an important role in virulence during Fusarium crown rot. An over-representation of genes involved in the phenylalanine, tryptophan and tyrosine biosynthesis pathways was observed. This was confirmed through metabolite analyses that demonstrated tryptamine and serotonin levels are induced after F. pseudograminearum inoculation. Conclusions: Overall, the observed host response in bread wheat to F. pseudograminearum during early infection exhibited enrichment of processes related to pathogen perception, defence signalling, transport and metabolism and deployment of chemical and enzymatic defences. Additional functional analyses of candidate genes should reveal their roles in disease resistance or susceptibility. Better understanding of host responses contributing to resistance and/or susceptibility will aid the development of future disease improvement strategies against this important plant pathogen.

Novel nomogram combining depth of invasion and size can accurately predict the risk for regional nodal metastases for appendiceal neuroendocrine tumors (A-NET).

INTRODUCTION: The need for regional lymphadenectomy for treating appendiceal neuroendocrine tumors (A-NET) is determined by the risk of nodal metastasis. Current guidelines for A-NET are solely based on tumor size. Methods Patients with A-NET from 1988 to 2012 were identified from the SEER registry. The depth of invasion was defined as limited to the lamina propria (LP), invading the muscularis propria (MP), and through the serosa (TS). RESULTS: A total of 418 patients were included; the majority were female, white, and node-negative. On univariate and multivariable, the risk of nodal metastasis was associated with age, size, depth of invasion, and extent of surgery. The model predicted the likelihood of nodal metastasis, with an area under the curve of 0.89. On survival analysis, age and tumor size predicted the survival in A-NET. In a Cox regression model, they continued to predict survival. These data were utilized to create a nomogram to predict the risk of nodal metastases. CONCLUSION: This nomogram, accurately predicts the risk of regional nodal metastases in A-NET. In addition to providing valuable information on risk for regional nodal metastases, the depth of invasion is also predictive of survival for A-NET.

Impact of malnutrition on gastrointestinal surgical patients.

BACKGROUND: The accurate diagnosis of malnutrition is imperative if we are to impact outcomes in the malnourished. The American Society of Parenteral and Enteral Nutrition (ASPEN) and Academy of Nutrition and Dietetics (AND), in an attempt to address this issue, have provided evidence-based criteria to diagnose malnutrition. The purpose of this study was to validate the ASPEN/AND criteria in a cohort of patients from a single high-volume surgical oncology unit. METHODS: Patients undergoing major abdominal surgery from June 2013 to March 2015 were classified by their nutritional status using the ASPEN/AND criteria. RESULTS: A total of 490 patients were included. Median age was 64 y, a majority were female (50.6%), white (60.2%), underwent elective procedures (77.6%), had a Charlson comorbidity score (CCS) of 3-5 (40.0%), and a Clavien-Dindo complication (CDC) grade of 0-II (81.2%). A total of 93 (19.0%) patients were classified as moderately/severely malnourished. On univariate analysis, malnourished patients were more likely to be older, undergo emergent procedures, and have a CCS >5 (P < 0.05). Malnutrition was also associated with a longer postoperative length of stay (LOS), higher cost, higher in-hospital mortality, more severe complications, and higher readmission rates (P < 0.05). Multivariate analysis reaffirmed the association between malnutrition, LOS (odds ratio [OR] = 1.67), and cost (OR = 2.49), P < 0.05. Complications (OR = 1.35), mortality rates (OR = 3.05), and readmission rates (OR = 1.34) P > 0.05 failed to reach significance. CONCLUSIONS: Malnutrition worsens LOS and cost. Utilization of standardized criteria consistently identifies patients at risk of negative outcomes who may benefit from perioperative nutritional support.

Patterns of node mapping differ for axial and extremity primary cutaneous melanoma: A case for a more selective use of pre-operative imaging.

PURPOSE: Preoperative lymphoscintigraphy for sentinel lymph node mapping in melanoma improves the ability to locate nodes. However, it still remains unclear whether this step is required for all patients. METHODS: Patients diagnosed with cutaneous melanoma from 1996 to 2012 were identified. Exclusion criteria were in situ disease, metastatic disease, or no SLN biopsy. RESULTS: 214 patients were evaluated. Median age was 57 years, the majority were male (59.8%), white (97.2%), and stage I (60.7%). SLN revealed metastatic disease in 14.5% of patients. The most common primary site was the trunk (43.4%) followed by head and neck (21%), upper extremity (19.2%), and lower extremity (16.4%). Multiple lymphatic basins were most common for head and neck lesions (66.7%) followed by those on the trunk (28.8%), with fewer identified when lower (11.4%), and upper extremities were involved (4.2%). When comparison was restricted to extremity vs. axial, a single basin was noted in 94.5% vs. 59.9% of patients, p < 0.0001. For all extremity lesions the SLN was located in the primary basin. Additional sites included in-transit (popliteal) and second tier basins. The only melanomas with bilateral or contralateral SLN were axial melanomas. CONCLUSIONS: Patients with axial melanomas benefit most from lymphoscintigraphy. This step may not be required for extremity melanoma.

Notch-1 promotes stemness and epithelial to mesenchymal transition in colorectal cancer.

Colorectal cancer (CRC) is the third leading cause of cancer death in the United States, resulting in an average of 50,000 deaths per year. Surgery and combination chemotherapy comprise current treatment strategies. However, curative options are limited if surgery and chemotherapy are unsuccessful. Several studies have indicated that CRC aggressiveness and potential for metastatic spread are associated with the acquisition of stem cell like properties. The Notch-1 receptor and its cognate signaling pathway is well known for controlling cell fate decisions and stem-cell phenotypes. Alterations in Notch receptors and Notch signaling has been reported for some colon cancers. Herein, we examine a potential role for Notch-1 signaling in CRC. In CRC patient samples, Notch-1 expression was increased in colon tumor tissue as compared with normal colon tissue. Retroviral transduction of constitutively active Notch-1 (ICN1) into the colon tumor cell line HCT-116 resulted in increased expression of the EMT/stemness associated proteins CD44, Slug, Smad-3, and induction of Jagged-1 expression. These changes in ICN1 expressing cells were accompanied by increased migration and increased anchorage independent growth by 2.5-fold and 23%, respectively. Experiments with the pan-Notch inhibitor DAPT, and soluble Jagged-1-Fc protein provided evidence that Notch-1 signaling activates CD44, Slug, and Smad-3 via a cascade of other Notch-receptors through induction of Jagged-1 expression. These data indicate a key role for Notch signaling in the phenotype of CRC and suggest that targeting of Notch signaling may be of therapeutic value in colon cancers.

Gene loss in the fungal canola pathogen Leptosphaeria maculans.

Recent comparisons of the increasing number of genome sequences have revealed that variation in gene content is considerably more prevalent than previously thought. This variation is likely to have a pronounced effect on phenotypic diversity and represents a crucial target for the assessment of genomic diversity. Leptosphaeria maculans, a causative agent of phoma stem canker, is the most devastating fungal pathogen of Brassica napus (oilseed rape/canola). A number of L. maculans genes are known to be present in some isolates but lost in the others. We analyse gene content variation within three L. maculans isolates using a hybrid mapping and genome assembly approach and identify genes which are present in one of the isolates but missing in the others. In total, 57 genes are shown to be missing in at least one isolate. The genes encode proteins involved in a range of processes including oxidative processes, DNA maintenance, cell signalling and sexual reproduction. The results demonstrate the effectiveness of the method and provide new insight into genomic diversity in L. maculans.

Identification and characterization of more than 4 million intervarietal SNPs across the group 7 chromosomes of bread wheat.

Despite being a major international crop, our understanding of the wheat genome is relatively poor due to its large size and complexity. To gain a greater understanding of wheat genome diversity, we have identified single nucleotide polymorphisms between 16 Australian bread wheat varieties. Whole-genome shotgun Illumina paired read sequence data were mapped to the draft assemblies of chromosomes 7A, 7B and 7D to identify more than 4 million intervarietal SNPs. SNP density varied between the three genomes, with much greater density observed on the A and B genomes than the D genome. This variation may be a result of substantial gene flow from the tetraploid Triticum turgidum, which possesses A and B genomes, during early co-cultivation of tetraploid and hexaploid wheat. In addition, we examined SNP density variation along the chromosome syntenic builds and identified genes in low-density regions which may have been selected during domestication and breeding. This study highlights the impact of evolution and breeding on the bread wheat genome and provides a substantial resource for trait association and crop improvement. All SNP data are publically available on a generic genome browser GBrowse at www.wheatgenome.info.

Brachypodium as an emerging model for cereal-pathogen interactions.

BACKGROUND: Cereal diseases cause tens of billions of dollars of losses annually and have devastating humanitarian consequences in the developing world. Increased understanding of the molecular basis of cereal host-pathogen interactions should facilitate development of novel resistance strategies. However, achieving this in most cereals can be challenging due to large and complex genomes, long generation times and large plant size, as well as quarantine and intellectual property issues that may constrain the development and use of community resources. Brachypodium distachyon (brachypodium) with its small, diploid and sequenced genome, short generation time, high transformability and rapidly expanding community resources is emerging as a tractable cereal model. SCOPE: Recent research reviewed here has demonstrated that brachypodium is either susceptible or partially susceptible to many of the major cereal pathogens. Thus, the study of brachypodium-pathogen interactions appears to hold great potential to improve understanding of cereal disease resistance, and to guide approaches to enhance this resistance. This paper reviews brachypodium experimental pathosystems for the study of fungal, bacterial and viral cereal pathogens; the current status of the use of brachypodium for functional analysis of cereal disease resistance; and comparative genomic approaches undertaken using brachypodium to assist characterization of cereal resistance genes. Additionally, it explores future prospects for brachypodium as a model to study cereal-pathogen interactions. CONCLUSIONS: The study of brachypodium-pathogen interactions appears to be a productive strategy for understanding mechanisms of disease resistance in cereal species. Knowledge obtained from this model interaction has strong potential to be exploited for crop improvement.

Radiotherapy associated with improved survival for high-grade sarcoma of the extremity.

BACKGROUND: The impact of radiotherapy on local control in limb-preserving surgery for high-risk sarcoma has been well studied. However, the impact of the use and timing of radiation therapy on survival is unclear. METHODS: From 1988 to 2010, patients with Stage III extremity sarcoma were identified within the SEER registry and cohorts were created using propensity score matching between irradiated and non-irradiated groups. RESULTS: A total of 2,606 patients were identified, with a median age of 59 years a majority were white (81%), male (54%), received radiotherapy (78%), and had lower extremity (80%) sarcomas. The most common subtype was fibrohistiocytic (29.8%). Patients treated with radiotherapy were younger (57.2 vs. 60.3 years) and differed in subtype compared to those untreated. The matched cohorts were better balanced for all factors. Radiation therapy was associated with a 5% 5-year survival advantage on univariate analysis for both the unmatched (P = 0.002) and matched cohorts (P = 0.01). On multivariate analysis radiotherapy was associated with a 20% and 30% survival advantage for the matched and unmatched cohorts, respectively (P ≤ 0.02). The timing of radiotherapy did not affect survival. CONCLUSIONS: Radiotherapy, regardless of the timing, is associated with improved survival in high-risk sarcoma.