Contralateral regional recurrence after elective unilateral neck irradiation in oropharyngeal carcinoma: A literature-based critical review

Publication date: Available online 21 July 2017
Source:Cancer Treatment Reviews
Author(s): Abrahim Al-Mamgani, Erik van Werkhoven, Arash Navran, Baris Karakullukcu, Olga Hamming-Vrieze, Melanie Machiels, Lilly-Ann van der Velden, Wouter V. Vogel, W. Martin Klop
Background: The head and neck region has rich regional lymphatic network, with a theoretical risk on contralateral metastasis from oropharyngeal cancer (OPC). There is a long-standing convention to irradiate the great majority of these tumors electively to both sides of the neck to reduce the risk of contralateral regional failure (cRF), but this can induce significant toxicity. We aimed to identify patient groups where elective contralateral irradiation may safely be omitted.Methods: PubMed and EMBASE were searched for original full-text articles in English with a combination of search terms related to the end points: cRF in OPC primarily treated by radiotherapy only to the ipsilateral neck and identifying predictive factors for increased incidence of cRF. The data from the identified studies were pooled, the incidence of cRF was calculated and the correlation with different predictive factors was investigated.Results: Eleven full-text articles met the inclusion criteria. In these studies, 1116 patients were treated to the ipsilateral neck alone. The mean incidence of cRF was 2.42% (range 0-5.9%, 95% CI 1.6-3.5%). The incidence of cRF correlated only with T-stage (p=0.008), and involvement of midline (p=0.001). However, the significant correlation with T-stage can be explained by the very low incidence of cRF among T1 (0.77%), and disappeared when the incidence of cRF was compared between T2, T3,and T4 (p=0.344).Conclusion: The incidence of cRF in patients with OPC is very low, with involvement of midline providing the most significant prognosticator. These results call for trials on unilateral elective irradiation in selected groups.



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Dual MET and ERBB inhibition overcomes intra-tumor plasticity in osimertinib resistant advanced non-small cell lung cancer (NSCLC)

Abstract

BackgroundThird-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as osimertinib are the last line of targeted treatment for metastatic non-small cell lung cancer (NSCLC) EGFR-mutant harboring T790M. Different mechanisms of acquired resistance to third-generation EGFR-TKIs have been proposed. It is therefore crucial to identify new and effective strategies to overcome successive acquired mechanisms of resistance.MethodsFor Amplicon-seq analysis, samples from the index patient (primary and metastasis lesions at different timepoints) as well as the patient derived orthotopic xenograft (PDOX) tumors corresponding to the different treatment arms were used. All samples were formalin-fixed paraffin-embedded (FFPE), selected and evaluated by a pathologist. For ddPCR, twenty patients diagnosed with NSCLC at baseline or progression to different lines of TKI therapies were selected. FFPE blocks corresponding to either primary tumor or metastasis specimens were used for analysis. For single cell analysis orthotopically grown metastases were dissected from the brain of an athymic nu/nu mouse and cryopreserved at -80 °C.ResultsIn a brain metastasis lesion from a NSCLC patient presenting an EGFR T790M mutation we detected MET gene amplification after prolonged treatment with osimertinib. Importantly, the combination of capmatinib (c-MET inhibitor) and afatinib (ErbB-1/2/4 inhibitor) completely suppressed tumor growth in mice orthotopically injected with cells derived from this brain metastasis. In those mice treated with capmatinib or afatinib as monotherapy we observed the emergence of KRAS G12C clones. Single cell gene expression analyses also revealed intratumor heterogeneity, indicating the presence of a KRAS-driven subclone. We also detected low frequent KRAS G12C alleles in patients treated with various EGFR-TKIs.ConclusionAcquired resistance to subsequent EGFR TKI treatment lines in EGFR-mutant lung cancer patients may induce genetic plasticity. We assess the biological insights of tumor heterogeneity in an osimertinib-resistant tumor with acquired MET-amplification and propose new treatment strategies in this situation.

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Open access to journal articles in oncology: Current situation and citation impact

Abstract

Background:Recent years have seen numerous efforts and resources devoted to the development of open access (OA), but the current OA situation of the oncology literature remains unknown. We conducted this cross-sectional study to determine the current share and provision methods of OA in the field of oncology, identify predictors of OA status (OA vs. non-OA), and study the association between OA and citation counts.Materials and Methods:PubMed was searched for oncology-related, peer-reviewed journal articles published in December 2014. Google, Google Scholar, PubMed, ResearchGate, OpenDOAR and OAIster were manually checked to assess the OA status of each included article. Citation data were extracted from Web of Science, Scopus and Google Scholar. Descriptive statistics were used to summarise the OA proportion (primary outcome) and OA provision methods. Multivariable logistic regression and multilevel generalised linear model analyses were performed to study predictors of OA status and the association between OA and citation counts, respectively.Results:In a random sample of 1000 articles, 912 were deemed eligible and therefore included. Of these, the full-texts of 530 articles (58.1%; 95% CI: 54.9 to 61.3) were freely available online: 314 (34.4%) were available from publishers ("Gold road" to OA), 424 (46.5%) were available via self-archiving ("Green road" to OA). According to multivariable regression analyses, impact factor, publisher type, language, research type, number of authors, continent of origin, and country income were significant predictors of articles' OA status; OA articles received a citation rate 1.24 times the incidence rate for non-OA articles (95% CI: 1.05 to 1.47; P=0.012).Conclusions:Based on our sample, in the field of oncology, 42% of recent journal articles are behind the pay-wall (non-OA) one year after publication; the "Green road" of providing OA is more common than the "Gold road"; OA is associated with higher citation counts.

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BET inhibitors: A Novel Epigenetic Approach

Abstract

Epigenetics has been defined as "the structural adaptation of chromosomal regions so as to register, signal or perpetuate altered activity states." Currently, several classes of anticancer drugs function at the epigenetic level, including inhibitors of DNA methyltransferase, histone deacetylase (HDAC), lysine-specific demethylase 1 (LSD1), zeste homolog 2 (EZH2), and bromodomain and extra-terminal motif (BET) proteins.BET proteins have multiple functions, including the initiation and elongation of transcription and cell cycle regulation. In recent years, inhibitors of BET proteins have been developed as anticancer agents. These inhibitors exhibit selectivity for tumor cells by preferentially binding to superenhancers, noncoding regions of DNA critical for the transcription of genes which determine a cell's identity. Preclinical research on BET inhibitors has identified them as a potential means of targeting MYC.Early clinical trials with BET inhibitors have had mixed results, with few responses in both hematologic and solid tumors that tend to be short-lived. Toxicities have included severe, thrombocytopenia, fatigue, nausea, vomiting, and diarrhea; GI side effects, fatigue, and low grade dysgeusia have limited compliance. However, preclinical data suggests that BET inhibitors may have a promising future in combination with other agents. They appear to be able to overcome resistance to targeted agents and have strong synergy with immune checkpoint inhibitors as well as with multiple epigenetic agents, particularly HDAC inhibitors. In many instances, BET and HDAC inhibitors were synergistic at reduced doses, suggesting a potential means of avoiding the overlapping toxicities of the two drug classes.BET inhibitors provide a novel approach to epigenetic anticancer therapy. However, to date they appear to have limited efficacy as single agents. A focus on BET inhibitors in combination with other drugs such as targeted and/or as other epigenetic agents is warranted, due to limited monotherapy activity, including pharmacodynamic correlatives differential activity amongst select drug combinations.

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Feasibility of olanzapine, multi acting receptor targeted antipsychotic agent, for the prevention of emesis caused by continuous cisplatin- or ifosfamide-based chemotherapy

Summary

Background To determine the feasibility and efficacy of olanzapine, which is approved by the Pharmaceuticals and Medical Devices Agency as multi acting receptor targeted antipsychotic agent of the thienobenzodiazepine class, for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients undergoing continuous five-day chemotherapy. Patients and methods This study was a prospective dose escalation study at a single center (UMIN ID: UMIN000015386). Patients received a combination of adriamycin and ifosfamide (AI) or a combination of bleomycin, etoposide, and cisplatin (BEP). On days 1–5, all patients received intravenous granisetron (1 mg) and intravenous dexamethasone sodium phosphate (24 mg). Olanzapine was administrated on day-1 to day5 at bedtime. The dose of olanzapine followed a dose-escalation scheme, with monitoring of safety and tolerability at each dose. A 3 + 3 cohort design was used, with three to six patients per cohort. Results Nine patients were enrolled (three for each cohort). No patients experienced dose-limiting toxicity (DLT). The most frequent adverse events were dry mouth and constipation. In each cohort, the maximum severity of nausea was Grade 2, and no patients experienced a vomiting episode. Conclusion A 2.5 mg/day dosage of olanzapine is sufficient to prevent from CINV in Japanese patients receiving continuous five-day chemotherapy. A dose of 10 mg/day, which is recommended by international CINV guidelines, is also tolerated. If CINV is not controlled by an initial dose of 2.5 mg/day of olanzapine, dosage escalation is encouraged. Future studies should compare olanzapine with aprepitant.

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Copper (II) complexes of bidentate ligands exhibit potent anti-cancer activity regardless of platinum sensitivity status

Summary

Insensitivity to platinum, either through inherent or acquired resistance, is a major clinical problem in the treatment of many solid tumors. Here, we explored the therapeutic potential of diethyldithiocarbamate (DDC), pyrithione (Pyr), plumbagin (Plum), 8-hydroxyquinoline (8-HQ), clioquinol (CQ) copper complexes in a panel of cancer cell lines that differ in their sensitivity to platins (cisplatin/carboplatin) using a high-content imaging system. Our data suggest that the copper complexes were effective against both platinum sensitive (IC₅₀ ~ 1 μM platinum) and insensitive (IC₅₀ > 5 μM platinum) cell lines. Furthermore, copper complexes of DDC, Pyr and 8-HQ had greater therapeutic activity compared to the copper-free ligands in all cell lines; whereas the copper-dependent activities of Plum and CQ were cell-line specific. Four of the copper complexes (Cu(DDC)₂, Cu(Pyr)₂, Cu(Plum)₂ and Cu(8-HQ)₂) showed IC₅₀ values less than that of cisplatin in all tested cell lines. The complex copper DDC (Cu(DDC)₂) was selected for in vivo evaluation due to its low nano-molar range activity in vitro and the availability of an injectable liposomal formulation. Liposomal (Cu(DDC)₂) was tested in a fast-growing platinum-resistant A2780-CP ovarian xenograft model and was found to achieve a statistically significant reduction (50%; p < 0.05) in tumour size. This work supports the potential use of copper-based therapeutics to treat cancers that are insensitive to platinum drugs.

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Interview with Thomas Powles: The use of durvalumab in urothelial cancer - the latest strides in immuno-oncology

Future Oncology, Ahead of Print.


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Necrotizing eosinophilic granulomatous lymphadenitis with ring- and C-shaped granulomas—an underrecognized specific manifestation of nodal Churg-Strauss syndrome

Abstract

Nodal involvement as the main or prominent clinical manifestation of Churg-Strauss Syndrome (CSS) is uncommon but is being recognized with increasing frequency. Lymph node biopsies are only obtained in CSS cases in which the classic clinical and serologic manifestations of the disease are not clear, and thus the nodal biopsy becomes crucial for recognizing a disorder associated with severe morbidity and mortality. Unfortunately, lymph node pathologists are rarely confronted with this disease, and detailed descriptions of pathologic findings in nodal CSS are scant, with only one previous detailed report. We confirmed the specificity of the findings described in the previous report, and expanded the morphologic and immunophenotypic features of nodal CSS, including a possible pathogenetic role of IgG4. The diagnosis allowed successful treatment of symptoms that had plagued the patient for over 2 years and allowed the rapid recognition of a potentially fatal acute alveolar hemorrhage that occurred after the patient underwent an aortic valve replacement for bacterial endocarditis. Treatment with anti-interleukin-5 humanized monoclonal antibody mepolizumab allowed decreasing the risk of infection and poor healing associated with high-dose steroids and cyclophosphamide.

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Insurance Clearance for Early-Phase Oncology Clinical Trials Following the Affordable Care Act

Purpose: The Affordable Care Act (ACA) required that private insurance plans allow clinical trial participation and cover standard-of-care costs, but the impact of this provision has not been well-characterized. We assessed rates of insurance clearance for trial participation within our large early-phase clinical trials program, before and after implementation of the requirement.

Experimental Design: We analyzed the departmental database for the Clinical Center for Targeted Therapy (CCTT) at MD Anderson Cancer Center (Houston, TX). Among patients referred for sponsored trials, we described rates of insurance clearance and prolonged time to clearance (at least 14 days) from July 2012 to June 2013 (baseline), July 2013–December 2013 (following CCTT staffing changes in July 2103), and January 2014–June 2015 (following implementation of the ACA). We used multivariable logistic regression models to compare rates across these time periods.

Results: We identified 2,404 referrals for insurance clearance. Among privately insured patients, insurance clearance rates were higher for those referred from January 2014 to June 2015 than for those referred from July 2012 to June 2013 (OR, 4.72; 95% CI, 2.96–7.51). There was no association between referral period and clearance rates for Medicare/Medicaid patients (P = 0.25). Referral from January 2014 to June 2015 was associated with lower rates of prolonged clearance among both privately insured (OR 0.57; 95% CI, 0.38–0.86) and Medicare/Medicaid patients (OR 0.39; 95% CI, 0.19–0.83).

Conclusion: Within our large early-phase clinical trials program, insurance clearance rates among privately insured patients improved following implementation of the ACA's requirement for coverage of standard-of-care costs. Clin Cancer Res; 23(15); 1–8. ©2017 AACR.

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JAK1/STAT3 activation through a proinflammatory cytokine pathway leads to resistance to molecularly targeted therapy in non-small cell lung cancer

Molecularly targeted drugs have yielded significant therapeutic advances in oncogene-driven non-small cell lung cancer (NSCLC), but a majority of patients eventually develop acquired resistance. Recently, the relation between proinflammatory cytokine interleukin-6 (IL6) and resistance to targeted drugs has been reported. We investigated the functional contribution of IL6 and the other members of IL6 family proinflammatory cytokine pathway to resistance to targeted drugs in NSCLC cells. In addition, we examined the production of these cytokines by cancer cells and cancer-associated fibroblasts (CAFs). We also analyzed the prognostic significance of these molecule expressions in clinical NSCLC samples. In NSCLC cells with acquired resistance to targeted drugs, we observed activation of the IL6-cytokine pathway and STAT3 along with epithelial-to-mesenchymal transition (EMT) features. In particular, IL6 family cytokine oncostatin-M (OSM) induced a switch to the EMT phenotype and protected cells from targeted drug-induced apoptosis in OSM receptors (OSMRs)/JAK1/STAT3-dependent manner. The cross-talk between NSCLC cells and CAFs also preferentially activated the OSM/STAT3 pathway via a paracrine mechanism and decreased sensitivity to targeted drugs. The selective JAK1 inhibitor filgotinib effectively suppressed STAT3 activation and OSMR expression, and co-targeting inhibition of the oncogenic pathway and JAK1 reversed resistance to targeted drugs. In the analysis of clinical samples, OSMR gene expression appeared to be associated with worse prognosis in patients with surgically resected lung adenocarcinoma. Our data suggest that the OSMRs/JAK1/STAT3 axis contributes to resistance to targeted drugs in oncogene-driven NSCLC cells, implying that this pathway could be a therapeutic target.

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Vessel-Targeted Chemophototherapy with Cationic Porphyrin-Phospholipid Liposomes

Cationic liposomes have been used for targeted drug delivery to tumor blood vessels, via mechanisms that are not fully elucidated. Doxorubicin (Dox)-loaded liposomes were prepared that incorporate a cationic lipid; 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), along with a small amount of porphyrin-phospholipid (PoP). Near infrared (NIR) light induced release of entrapped Dox via PoP-mediated DOTAP photo-oxidation. The formulation was optimized to enable extremely rapid NIR light-triggered Dox release (i.e. in 15 seconds), while retaining reasonable serum stability. In vitro, cationic PoP liposomes readily bound both to MIA PaCa-2 human pancreatic cancer cells and human vascular endothelial cells. When administered intravenously, cationic PoP liposomes were cleared from circulation within minutes, with most accumulation in the liver and spleen. Fluorescence imaging revealed that some cationic PoP liposomes also localized at the tumor blood vessels. Compared to analogous neutral liposomes, strong tumor photo-ablation was induced with a single treatment of cationic PoP liposomes and laser irradiation (5 mg/kg Dox and 100 J/cm² NIR light). Unexpectedly, empty cationic PoP liposomes (lacking Dox) induced equally potent anti-tumor phototherapeutic effects as the drug loaded ones. A more balanced chemo- and photo- therapeutic response was subsequently achieved when anti-tumor studies were repeated using higher drug dosing (7 mg/kg Dox) and an ultralow fluence phototreatment (20 J/cm² NIR light). These results demonstrate the feasibility of vessel-targeted chemophototherapy using cationic PoP liposomes and also illustrate synergistic considerations.

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WILMS TUMOR NCAM-EXPRESSING CANCER STEM CELLS AS POTENTIAL THERAPEUTIC TARGET FOR POLYMERIC NANOMEDICINE

Cancer stem cells (CSC) form a specific population within the tumor that has been shown to have self-renewal and differentiation properties, increased ability to migrate and form metastases, and increased resistance to chemotherapy. Consequently, even a small number of cells remaining after therapy can repopulate the tumor and cause recurrence of the disease. CSCs in Wilms tumor, a pediatric renal cancer, were previously shown to be characterized by neural cell adhesion molecule (NCAM) expression. Therefore, NCAM provides a specific biomarker through which the CSC population in this tumor can be targeted. We have recently developed an NCAM-targeted nano-sized conjugate of paclitaxel bound to a biodegradable polyglutamic acid polymer. In this work, we examined the ability of the conjugate to inhibit Wilms tumor by targeting the NCAM-expressing CSCs. Results show that the conjugate selectively depleted the CSC population of the tumors and effectively inhibited tumor growth without causing toxicity. We propose that the NCAM-targeted conjugate could be an effective therapeutic for Wilms tumor.

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Autophagy inhibition improves sunitinib efficacy in pancreatic neuroendocrine tumors via a lysosome-dependent mechanism

Increasing the efficacy of approved systemic treatments in metastasized pancreatic neuroendocrine tumors (PanNETs) is an unmet medical need. The anti-angiogenic tyrosine kinase inhibitor sunitinib is approved for PanNET treatment. Additionally, sunitinib is a lysosomotropic drug and such drugs can induce lysosomal membrane permeabilization as well as autophagy. We investigated sunitinib-induced autophagy as a possible mechanism of PanNET therapy resistance. Sunitinib accumulated in lysosomes and induced autophagy in PanNET cell lines. Adding the autophagy inhibitor chloroquine reduced cell viability in cell lines and in primary cells isolated from PanNET patients. The same treatment combination reduced tumor burden in the Rip1Tag2 transgenic PanNET mouse model. The combination of sunitinib and chloroquine reduced recovery and induced apoptosis in vitro, whereas single treatments did not. Knockdown of key autophagy proteins in combination with sunitinib showed similar effect as chloroquine. Sunitinib also induced lysosomal membrane permeabilization, which further increased in the presence of chloroquine or knockdown of lysosome-associated membrane protein (LAMP2). Both combinations led to cell death. Our data indicate that chloroquine increases sunitinib efficacy in PanNET treatment via autophagy inhibition and lysosomal membrane permeabilization. We suggest that adding chloroquine to sunitinib treatment will increase efficacy of PanNET treatment and that such patients should be included in respective ongoing clinical trials.

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Decitabine Priming Enhances Mucin 1 Inhibition Mediated Disruption of Redox Homeostasis in Cutaneous T-cell Lymphoma

Cutaneous T-cell lymphoma (CTCL) is a heterogeneous neoplasm and patients with relapsed/refractory disease exhibit resistance to standard therapies. We have previously demonstrated that the MUC1-C oncoprotein plays a critical role in protection from oxidative stress in CTCL cells. Targeting of MUC1-C with a pharmacologic inhibitor, GO-203, was associated with apoptosis in CTCL. However, disease responses were incomplete underscoring the need for combinatorial strategies that could exploit the vulnerability of CTCL cells to oxidative signals. Cell lines, primary samples and xenograft models of CTCL were used to assess synergy of GO-203 with decitabine, a hypomethylating agent. Present studies demonstrate that exposure of CTCL cells to decitabine in combination with GO-203, increased the generation of reactive oxygen species (ROS) levels and decreased levels of scavenger molecules, NADP, NADPH, glutathione (GSH), and TIGAR, critical to intracellular redox homeostasis. Dual exposure to GO-203 and decitabine resulted in marked down-regulation of DNA methyl transferases demonstrating significant synergy of these agents in inducing global and gene specific hypomethylation. Accordingly, treatment with decitabine and GO-203 upregulated the ROS generating enzymes, NADPH oxidase 4 (Nox4) and Dual oxidase 2 (Duox2) potentially due to their effect on epigenomic regulation of these proteins. In concert with these findings, exposure to decitabine and GO-203 resulted in heightened apoptotic death in CTCL cell lines, patient derived primary samples and in a murine xenograft model. These findings indicate that decitabine intensifies MUC1-C inhibition induced redox imbalance and provides a novel combination of targeted and epigenetic agents for patients with CTCL.

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Quercetin targets hnRNPA1 to overcome enzalutamide resistance in prostate cancer cells

Prostate cancer remains dependent on androgen receptor signaling even after castration. Aberrant androgen receptor signaling in castration resistant prostate cancer is mediated by mechanisms such as alterations in the androgen receptor and activation of interacting signaling pathways. Clinical evidence confirms that resistance to the next generation anti-androgen, enzalutamide, may be mediated to a large extent by alternative splicing of the androgen receptor to generate constitutively active splice variants such as AR-V7. The splice variants AR-V7 and Arv567es have been implicated in the resistance to not only enzalutamide, but also to abiraterone and other conventional therapeutics such as taxanes. Numerous studies including ours suggest that splicing factors such as hnRNPA1 promote the generation of AR-V7, thus contributing to enzalutamide resistance in prostate cancer cells. In the present study, we discovered that quercetin, a naturally occurring polyphenolic compound, reduces the expression of hnRNPA1, and consequently, that of AR-V7. The suppression of AR-V7 by quercetin resensitizes enzalutamide-resistant prostate cancer cells to treatment with enzalutamide. Our results indicate that quercetin downregulates hnRNPA1 expression, downregulates the expression of AR-V7, antagonizes androgen receptor signaling, and resensitizes enzalutamide-resistant prostate cancer cells to enzalutamide treatment in vivo in mouse xenografts. These findings demonstrate that suppressing the alternative splicing of the androgen receptor may have important implications in overcoming the resistance to next-generation anti-androgen therapy.

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The IGF1R/INSR inhibitor BI 885578 selectively inhibits growth of IGF2-overexpressing colorectal cancer tumors and potentiates the efficacy of anti-VEGF therapy

Clinical studies of pharmacological agents targeting the insulin like growth factor (IGF) pathway in unselected cancer patients have so far demonstrated modest efficacy outcomes, with objective responses being rare. As such, the identification of selection biomarkers for enrichment of potential responders represents a high priority for future trials of these agents. Several reports have described high IGF2 expression in a subset of colorectal cancers (CRC), with focal IGF2 amplification being responsible for some of these cases. We defined a novel cutoff for IGF2 overexpression based on differential expression between colorectal tumors and normal tissue samples. Analysis of two independent CRC data sets revealed IGF2 to be overexpressed at a frequency of 13-22%. An in vitro screen of 34 CRC cell lines revealed IGF2 expression to significantly correlate with sensitivity to the IGF1R/INSR inhibitor BI 885578. Furthermore, autocrine IGF2 constitutively activated IGF1R and Akt phosphorylation, which was inhibited by BI 885578 treatment. BI 885578 significantly delayed the growth of IGF2-high CRC xenograft tumors in mice, whilst combination with a vascular endothelial growth factor-A (VEGF-A) antibody increased efficacy and induced tumor regression. Besides CRC, IGF2 overexpression was detected in more than 10% of bladder carcinoma, hepatocellular carcinoma and non-small cell lung cancer patient samples. Meanwhile, IGF2-high non-CRC cancer cells lines displayed constitutive IGF1R phosphorylation and were sensitive to BI 885578. Our findings suggest that IGF2 may represent an attractive patient selection biomarker for IGF pathway inhibitors and that combination with VEGF-targeting agents may further improve clinical outcomes.

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MYC-regulated Mevalonate Metabolism Maintains Brain Tumor Initiating Cells

Metabolic dysregulation drives tumor initiation in a subset of glioblastomas harboring isocitrate dehydrogenase (IDH) mutations, but metabolic alterations in glioblastomas with wildtype IDH are poorly understood. MYC promotes metabolic reprogramming in cancer, but targeting MYC has proven notoriously challenging. Here, we link metabolic dysregulation in patient-derived brain tumor initiating cells (BTICs) to a nexus between MYC and mevalonate signaling, which can be inhibited by statin or 6-fluoromevalonate treatment. BTICs preferentially express mevalonate pathway enzymes, which we find regulated by novel MYC binding sites, validating an additional transcriptional activation role of MYC in cancer metabolism. Targeting mevalonate activity attenuated RAS-ERK-dependent BTIC growth and self-renewal. In turn, mevalonate created a positive feed-forward loop to activate MYC signaling via induction of miR-33b. Collectively, our results argue that MYC mediates its oncogenic effects in part by altering mevalonate metabolism in gloma cells, suggesting a therapeutic strategy in this setting.

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Mathematical modeling of tumor-tumor distant interactions supports a systemic control of tumor growth

Interactions between different tumors within the same organism have major clinical implications, especially in the context of surgery and metastatic disease. Three main explanatory theories (competition, angiogenesis inhibition and proliferation inhibition) have been proposed but precise determinants of the phenomenon remain poorly understood. Here we formalized these theories into mathematical models and performed biological experiments to test them with empirical data. In syngeneic mice bearing two simultaneously implanted tumors, growth of only one of the tumors was significantly suppressed (61% size reduction at day 15, pMajor findings In mice bearing two tumors implanted simultaneously, tumor growth was suppressed in one of the two tumors. Three theories of this phenomenon were advanced and assessed against the data. As formalized, a model of competition for nutrients was not able to explain the growth behavior as well as indirect, angiogenesis-regulated inhibition or a third model based on direct systemic inhibition. This last model offers a depiction of concomitant resistance that provides an improved theoretical basis for tumor growth control and may also find utility in therapeutic planning to avoid post-surgery metastatic acceleration.

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Methods of Academic Course Planning for Cancer Biology Ph.D. Students to Enhance Knowledge of Clinical Oncology

Little is known about how clinical oncology concepts are taught to Ph.D. students or the most effective methods of doing so. In this study, electronic surveys were sent to faculty and students at Ph.D. training programs, assessing their institution's methods of clinical oncology education and their perspective on optimal approaches to clinical oncology education. Only 40.0% of students reported any clinical oncology component to their institution's training, and only 26.5% had a clinician on their graduate advisory committee. Forty-three percent of students believed that they had a good understanding for translating basic science research into clinical practice, and 77.2% of all participants believed dual degree M.D./Ph.D. students were superior to Ph.D. students in this regard. Lectures on clinical oncology research topics were the most valuable type of experience for all participants, and was also the most common type of experience utilized. Working with a clinician to develop a clinical trial with correlative endpoints was also highly valued, but was only utilized by approximately 10% of programs. Faculty rated the value of nearly all types of clinical oncology exposure significantly lower than did students. Inclusion of the approaches identified in this study is likely to enhance Ph.D. training in oncology-related disciplines.

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CIB2 negatively regulates oncogenic signaling in ovarian cancer via sphingosine kinase 1

Sphingosine kinase 1 (SK1) is a key regulator of the cellular balance between pro-apoptotic and pro-survival sphingolipids. Oncogenic signaling by SK1 relies on its localization to the plasma membrane, which is mediated by the calcium and integrin binding protein CIB1 via its Ca2+-myristoyl switch function. Here we show that another member of the CIB family, CIB2, plays a surprisingly opposite role to CIB1 in the regulation of SK1 signalling. CIB2 bound SK1 on the same site as CIB1, yet it lacks the Ca2+-myristoyl switch function. As a result, CIB2 blocked translocation of SK1 to the plasma membrane and inhibited its subsequent signaling, which included sensitization to TNFα-induced apoptosis and inhibition of Ras-induced neoplastic transformation. CIB2 was significantly down-regulated in ovarian cancer and low CIB2 expression was associated with poor prognosis in ovarian cancer patients. Notably, reintroduction of CIB2 in ovarian cancer cells blocked plasma membrane localization of endogenous SK1, reduces in vitro neoplastic growth and tumour growth in mice, and supressed cell motility and invasiveness both in vitro and in vivo. Consistent with the in vitro synergistic effects between the SK1 specific inhibitor SK1-I and standard chemotherapeutics, expression of CIB2 also sensitized ovarian cancer cells to carboplatin. Together, these findings identify CIB2 as a novel endogenous suppressor of SK1 signaling and potential prognostic marker and demonstrate the therapeutic potential of SK1 in this gynaecological malignancy.

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An essential role for the tumor suppressor Merlin in regulating fatty acid synthesis

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterized by the development of multiple tumors in the central nervous system, most notably schwannomas and meningiomas. Mutational inactivation of the NF2 gene encoding the protein Merlin is found in most sporadic and inherited schwannomas, but the molecular mechanisms underlying neoplastic changes in schwannoma cells remain unclear. We report here that NF2-deficient cells display elevated expression levels of key enzymes involved in lipogenesis and that this upregulation is caused by increased activity of Torc1. Inhibition or knockdown of fatty acid synthase (FASN), the enzyme that catalyzes the formation of palmitic acid from malonyl-CoA, drove NF2-deficient cells into apoptosis. Treatment of NF2-mutant cells with agents that inhibit the production of malonyl-CoA reduced their sensitivity to FASN inhibitors. Collectively, these results suggest that the altered lipid metabolism found in NF2-mutant cells renders them sensitive to elevated levels of malonyl-CoA, as occurs following blockade of fatty acid synthase, suggesting new targeted strategies in the treatment of NF2-deficient tumors.

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Breast cancer suppression by progesterone receptors is mediated by their modulation of estrogen receptors and RNA polymerase III

Greater than 50% of estrogen receptor (ER)-positive breast cancers co-express the progesterone receptor (PR), which can directly and globally modify ER action to attenuate tumor growth. However, whether this attenuation is mediated only through PR-ER interaction remains unknown. To address this question, we assessed tumor growth in ER/PR-positive PDX models of breast cancer where both natural and synthetic progestins were found to antagonize the mitogenic effects of estrogens. Probing the genome-wide mechanisms by which this occurs, we documented that chronic progestin treatment blunted ER-mediated gene expression up to 2-fold at the level of mRNA transcripts. Unexpectedly, <25% of all ER DNA binding events were affected by the same treatment. The PR cistrome displayed a bimodal distribution. In one group, >50% of PR binding sites were co-occupied by ER, with a propensity for both receptors to coordinately gain or lose binding in the presence of progesterone. In the second group, PR but not ER was associated with a large fraction of RNA polymerase III (Pol III)-transcribed tRNA genes, independent of hormone treatment. Notably, we discovered that PR physically associated with the Pol III holoenzyme. Select pre-tRNA and mature tRNA that colocalized with PR and POLR3A at their promoters were relatively decreased in estrogen+progestin treated tumors. Our results illuminate how PR may indirectly impede ER action by reducing the bioavailability of translational molecules needed for tumor growth.

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Utilizing circulating tumour DNA in radiation oncology

Emerging technologies for detection of circulating tumour DNA (ctDNA) are expanding the possibilities for clinical impact to patients with localized, potentially curable cancer. For such patients, ctDNA analysis could aid in prognostication, prediction of treatment response, longitudinal monitoring for adaptive treatment, and evaluation of minimal residual disease. Radiation oncologists currently have few tools at their disposal for predicting or rapidly assessing treatment efficacy. By reflecting the genetic and epigenetic makeup of tumours as well as dynamic changes with treatment, ctDNA as a biomarker for radiation response could enable new personalized treatment approaches.

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Men's Information-Seeking Behaviour Regarding Cancer Risk and Screening: A Meta-Narrative Systematic Review

Abstract

Objective

Preventive strategies are known to reduce cancer risk and incidence and improve prognosis. Men seldom seek medical information about cancer prevention and risk reduction. The aim of this meta-narrative systematic review was to critically appraise evidence from qualitative, quantitative, and mixed-methods studies that explored men's information-seeking behaviours in relation to cancer prevention and risk reduction.

Methods

MEDLINE, CINAHL Plus with Full Text, PsycINFO, PsycARTICLES, Psychology and Behavioral Sciences Collection, Education Full Text, and ERIC were systematically searched for studies published in English between January 1^st 2006 and May 30^th 2016. A total of 4,117 titles were identified; of which, 31 studies were included (21 qualitative studies, nine quantitative studies, and one mixed-methods study). The methodological quality of the studies was appraised using different tools.

Results

Most studies focused on screening for prostate (n=18) and colorectal cancer (n=7). The majority of men were passive information-gatherers rather than active information-seekers. Key sources of information included the internet for active information-seekers and healthcare professionals for passive information-gatherers. Barriers to information-seeking included information overload, embarrassment, and fear. Low literacy and health literacy levels were addressed in three studies and were identified as impediments to active information-seeking. Facilitators to information-seeking included family support, media, celebrity endorsements, and targeted information.

Conclusions

Men's information-seeking behaviour regarding cancer risk reduction, prevention, and screening is influenced by several factors. This necessitates targeted interventions aimed at raising awareness of cancer prevention and screening, whilst accounting for men's informational needs, preferred learning strategies, and literacy levels.

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Serum Bupivacaine Concentration After Periarticular Injection With a Mixture of Liposomal Bupivacaine and Bupivacaine HCl During Total Knee Arthroplasty.

Background and Objectives: A relatively new technique to reduce postoperative pain for total knee arthroplasty is to inject a mixture of 266 mg of liposomal bupivacaine and 125 mg of 0.25% bupivacaine HCl with epinephrine 1:300,000 around the knee joint at the time of surgery. Currently, no publications report serum bupivacaine concentrations over time after periarticular injection of liposomal mixed with free bupivacaine. This information is important to ensure safe serum bupivacaine concentrations are maintained especially when considering supplemental or rescue peripheral nerve blocks. Methods: A total of 40 subjects scheduled for primary unilateral total knee arthroplasty with intraoperative periarticular injection of the liposomal bupivacaine and bupivacaine HCl mixture were included. Total serum bupivacaine concentrations were measured after the last injection at selected time points and calculated by gas chromatography. Quantile regression techniques were used to analyze the data over time. This study is registered with ClinicalTrials.gov (ID NCT02626559). Results: Peak serum concentration ranged from 0.17 to 1.2 [mu]g/mL and occurred from 10 minutes to 48 hours. Across all time points, the 48-hour interval had the highest mean concentration of total serum bupivacaine at 0.55 [mu]g/mL (SD, 0.27). Quantile regression showed total serum bupivacaine concentrations increased over the 48 hours measured. None of the participants demonstrated signs or symptoms of local anesthetic toxicity. Conclusions: Total serum concentrations of bupivacaine after periarticular administration of liposomal bupivacaine mixed with bupivacaine HCl remained below the described toxicity threshold (2.5 [mu]g/mL) within the first 48 hours, and no patients demonstrated signs or symptoms of toxicity. However, peak serum concentration time was not achieved within the 48-hour interval. Additional studies are needed to describe the course of serum bupivacaine levels after 48 hours and to ascertain the risk of toxicity when combining this method of periarticular injection with peripheral nerve blocks. Copyright (C) 2017 by American Society of Regional Anesthesia and Pain Medicine.

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Thoracic Epidural Catheter Placement in a Preoperative Block Area Improves Operating Room Efficiency and Decreases Epidural Failure Rate.

Background and Objectives: The primary aim of this study was to review the impact of inserting thoracic epidural catheters in a preoperative block room setting on operating room efficiency. Methods: We conducted a retrospective preintervention/postintervention review of thoracic epidurals inserted over a 12-month period. The review included 6 months of data prior to implementation of the regional anesthesia block room and 6 months of data following implementation. The primary outcome measure was anesthesia-controlled operating room time, defined as time from patient arrival to the operating room to time of surgical site sterile preparation. Secondary measures included operating room waiting time for the patient arrival, thoracic epidural failure rate, and number of epidural insertion attempts. Results: Data from thoracic epidurals for 112 patients of preblock room and 142 patients of postblock room implementation were collected. Anesthesia-controlled operating room time was reduced by an average of 22.9 minutes per patient (95% confidence interval, 19.3-26.3 minutes; P

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Clinical and prognosis value of the CIMP status combined with MLH1 or p16 INK4a methylation in colorectal cancer

Abstract

Aberrant DNA methylation of CpG islands occurred frequently in CRC and associated with transcriptional silencing of key genes. In this study, the CIMP combined with MLH1 or p16 ^INK4a methylation status was determined in CRC patients and correlated with clinicopathological parameters and overall survival. Our data showed that CIMP+ CRCs were identified in 32.9% of cases and that CACNAG1 is the most frequently methylated promoter. When we combined the CIMP with the MLH1 or the p16 ^INK4a methylation status, we found that CIMP−/MLH1-U (37.8%) and CIMP−/p16 ^INK4a -U (35.4%) tumors were the most frequent among the four subtypes. Statistical analysis showed that tumor location, lymphovascular invasion, TNM stage, and MSI differed among the group of patients. Kaplan–Meier analyses revealed differences in overall survival according to the CIMP combined with MLH1 or p16 ^INK4a methylation status. In a multivariate analysis, CIMP/MLH1 and CIMP/p16 ^INK4a methylation statuses were predictive of prognosis, and the OS was longer for patients with tumors CIMP−/MLH1-M, as well as CIMP−/p16 ^INK4a -M. Furthermore, DNMT1 is significantly overexpressed in tumors than in normal tissues as well as in CIMP+ than CIMP− tumors. Our results suggest that tumor classification based on the CIMP status combined with MLH1 or p16 ^INK4a methylation is useful to predict prognosis in CRC patients.

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Clinical predictors of survival in patients with castration-resistant prostate cancer receiving sipuleucel-T cellular immunotherapy

Abstract

Background

We evaluated the patterns of progression and determined clinical predictors of survival in patients with castration-resistant prostate cancer (CRPCa) who received sipuleucel-T.

Methods

We retrospectively analyzed 56 consecutive patients with asymptomatic or minimally symptomatic CRPCa treated with sipuleucel-T. Age, number of bone metastases, history of prior systemic treatment, and alkaline phosphatase level (ALP) were tested as predictors of survival in a multivariate Cox proportional hazards regression model. The Kaplan–Meier method was used to estimate event-free probabilities.

Results

The 56 patients were a median age of 67 years (range 51–84 years). After sipuleucel-T treatment, 25 patients developed bone progression after a median of 22 months of follow-up (54% of patients were event free at 2 years) and 10% (6/56 patients) developed rapid progression. Eleven deaths were observed after a median of 28 months of follow-up. Forty-eight patients were included in the multivariate analysis for overall survival. The analysis showed that age >70 years (p = 0.012), number of bone metastases >20 (p = 0.018), prior systemic treatment (p = 0.018), and ALP level >90 IU/L (p = 0.010) significantly predicted worse overall survival. Two-year overall survival was 36% among the 16 patients with two or more of these factors and was 93% among the 32 patients with one or none of these factors (p = 0.0004).

Conclusions

CRPCa patients with age (>70 years), increased tumor burden in bone (>20 metastases and/or elevated ALP level), and/or prior systemic treatment are more likely to experience rapid deterioration after sipuleucel-T. These results need to be prospectively validated.

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Treatment outcome of patients with recurrent glioblastoma multiforme: a retrospective multicenter analysis

Abstract

Glioblastoma multiforme (GBM) universally recurs with dismal prognosis. We evaluated the efficacy of standard treatment strategies for patients with recurrent GBM (rGBM). From two centers in the Netherlands, 299 patients with rGBM after first-line treatment, diagnosed between 2005 and 2014, were retrospectively evaluated. Four different treatment strategies were defined: systemic treatment (SYST), re-irradiation (RT), re-resection followed by adjuvant treatment (SURG) and best supportive care (BSC). Median OS for all patients was 6.5 months, and median PFS (excluding patients receiving BSC) was 5.5 months. Older age, multifocal lesions and steroid use were significantly associated with a shorter survival. After correction for confounders, patients receiving SYST (34.8%) and SURG (18.7%) had a significantly longer survival than patients receiving BSC (39.5%), 7.3 and 11.0 versus 3.1 months, respectively [HR 0.46 (p < 0.001) and 0.36 (p < 0.001)]. Median survival for patients receiving RT (7.0%) was 9.2 months, but this was not significantly different from patients receiving BSC (p = 0.068). Patients receiving SURG compared to SYST had a longer PFS (9.0 vs. 4.3 months, respectively; p < 0.001), but no difference in OS was observed. After adjustments for confounders, patients with rGBM selected for treatment with SURG or SYST do survive significantly longer than patients who are selected for BSC based on clinical parameters. The value of reoperation versus systemic treatment strategies needs further investigation.

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Enhanced anticancer efficacy of histone deacetyl inhibitor, suberoylanilide hydroxamic acid, in combination with a phosphodiesterase inhibitor, pentoxifylline, in human cancer cell lines and in-vivo tumor xenografts.

Vorinostat [suberoylanilide hydroxamic acid (SAHA)], a histone deacetylase inhibitor, shows limited clinical activity against solid tumors when used alone. The methyl xanthine drug, pentoxifylline (PENT), has been described to have antitumor properties. The aim of this study was to look for the enhanced anticancer activities of both agents when used in combination at doses lower than their respective efficacy dose when used alone. We investigated the antitumor potential of this novel combination in vitro and in vivo. The combination index was assessed for these two drugs to look for synergistic antiproliferative activity against a broad spectrum of human cancer cell lines. Consistent additive to synergistic interactions were observed in HCT116 cells when PENT was combined with SAHA at all drug tested concentrations. The combination of SAHA and PENT induces chromatin condensation and apoptosis downstream of the pan histone deacetylase inhibition and phosphodiesterase regulation, leading to subsequent cell cycle arrest at their lower tested concentrations. Further, the ability of this combination to inhibit angiogenesis, both in vitro and in vivo, was examined and a significant inhibition in tube formation in HUVEC cells and neovascularization of Matrigel plug was observed. A significant inhibition in tumor growth was observed in severe combined immunodeficient mice bearing HCT116 (colon) and PC3 (prostate) human xenografts treated with SAHA (30 mg/kg, intraperitoneal) in combination with PENT (60 mg/kg, intraperitoneal), with no loss in body weight and 100% survival. In conclusion, these findings indicate the enhanced anticancer activity of SAHA in combination with PENT both in vitro and in vivo. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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miR-181a-2 downregulates the E3 ubiquitin ligase CUL4A transcript and promotes cell proliferation

Abstract

MiR-181a-2 plays a major role in cell proliferation both positively and negatively depending on tissue type by targeting several regulators 3′UTR regions. We have predicted several targets for miR-181a-2 through computational approaches and characterized one its interesting target, CUL4A, an E3 ubiquitin ligase. CUL4A regulates diverse functions in the cells including DNA repair, DNA replication, cell cycle, genomic stability through polyubiquitination of target proteins. Deregulation of both miR-181a-2 and CUL4A are reported in many cancerous cells, but the functional link between them is unknown. We show that miR-181a-5p binds to 3′UTR of CUL4A and regulates its transcripts levels in HEK293 cells through overexpression studies. In addition, by using MTT and Neutral red assays, we showed that miR-181a-2 overexpression increased the proliferation in HEK293 cells. Moreover, cell cycle analysis using flow cytometer revealed that an increase in S-phase cells upon the overexpression of miR-181a-2. Though several miRNAs are known to downregulate the CUL4A levels, here we show that miR-181a-2 also participates in the downregulation of CUL4A. Taken together, our data demonstrated that miR-181a-2 increases the cell proliferation in HEK293 cells possibly through the downregulation of CUL4A.

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Three-dimensional printing for patient counseling

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Carbon-ion radiotherapy for isolated para-aortic lymph node recurrence from colorectal cancer

Background

The safety and effectiveness of carbon-ion radiotherapy (CIRT) for isolated para-aortic lymph node (PALN) metastasis was evaluated retrospectively.

Methods

CIRT for isolated PALN metastasis from CRC was performed in 34 cases from June 2006 to August 2015 in our institute. A median dose of 52.8 Gy(RBE) (range, 48-52.8 Gy(RBE)) was delivered with a median daily dose of 4.4 Gy(RBE) (range, 4.0-4.4 Gy(RBE)).

Results

The median follow-up duration for all patients was 24.4 months (range, 7-82.8 months). There were 13 cases (38.2%) who achieved complete response after treatment. The local control rates at 2 and 3 years were 70.1% and 70.1%, respectively. The overall survival rates at 2 and 3 years were 83.3% and 63.0%, respectively. The 3-year survival rates for Stage I-III were 68.7%, while those for Stage IV was 0%. The overall survival of cases with rectal cancer or with high CA19-9 values pre-CIRT tended to be worse. The median survival period was 41.7 months. Twelve of the 34 patients survived for more than 3 years. There were no adverse effects of Grade 3 or higher.

Conclusions

CIRT for isolated PALN recurrence after curative resection for CRC appears effective and safe, and it is considered a promising therapy.

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Issue Information - TOC

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Issue Information - Ed Board

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Issue Information - Ed Board

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Three-dimensional printing for patient counseling

http://ift.tt/2uN12rc

Carbon-ion radiotherapy for isolated para-aortic lymph node recurrence from colorectal cancer

Background

The safety and effectiveness of carbon-ion radiotherapy (CIRT) for isolated para-aortic lymph node (PALN) metastasis was evaluated retrospectively.

Methods

CIRT for isolated PALN metastasis from CRC was performed in 34 cases from June 2006 to August 2015 in our institute. A median dose of 52.8 Gy(RBE) (range, 48-52.8 Gy(RBE)) was delivered with a median daily dose of 4.4 Gy(RBE) (range, 4.0-4.4 Gy(RBE)).

Results

The median follow-up duration for all patients was 24.4 months (range, 7-82.8 months). There were 13 cases (38.2%) who achieved complete response after treatment. The local control rates at 2 and 3 years were 70.1% and 70.1%, respectively. The overall survival rates at 2 and 3 years were 83.3% and 63.0%, respectively. The 3-year survival rates for Stage I-III were 68.7%, while those for Stage IV was 0%. The overall survival of cases with rectal cancer or with high CA19-9 values pre-CIRT tended to be worse. The median survival period was 41.7 months. Twelve of the 34 patients survived for more than 3 years. There were no adverse effects of Grade 3 or higher.

Conclusions

CIRT for isolated PALN recurrence after curative resection for CRC appears effective and safe, and it is considered a promising therapy.

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Issue Information - TOC

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The course of fear of cancer recurrence: Different patterns by age in breast cancer survivors.

Abstract

Objective

To examine the time course and predictors of fear of cancer recurrence (FCR) in breast cancer survivors over a period of 18 months after initial surgery.

Methods

Breast cancer patients (n = 267) were followed until 18 months after primary breast surgery. Shortly after surgery, participants completed the Life Orientation Test-Revised (LOT-R) to measure optimism and the Concerns about Recurrence Scale (CARS) to measure FCR. Mixed regression analysis was performed with age, optimism, marital status, education, type of surgery, with or without lymphectomy, chemotherapy, hormonal therapy, or radiotherapy, time since surgery and all interactions with time as predictors of FCR.

Results

The final model included a significant interaction between age and time since surgery and a main effect for optimism.

Conclusion

These results suggest that the course of FCR depends on the age of breast cancer survivors. Younger survivors showed an increase of fear during the first 1.5 years after breast surgery, whereas older survivors showed stable levels during the first 6 months after which it declined. Also, less optimistic survivors reported higher levels of FCR. Health care providers should pay (extra) attention to FCR in younger and less optimistic patients and offer psychological help when needed.

http://ift.tt/2ue0lUk

End-of-life experiences of family caregivers of deceased patients with cancer: A nation-wide survey

Abstract

Objectives

The purpose of this study was (1) to describe the end-of-life experience of family caregivers of cancer patients, (2) to describe talking about death and dying of the patient to minor children, and (3) to examine the association of family caregivers' experiences by their characteristics and talking about death and dying of the patient.

Methods

A cross-sectional nationwide survey of bereaved family caregivers was conducted. In total, 968 questionnaires were sent to bereaved family caregivers, and 711 were completed and returned. Fifty-three responses indicating patients had minor children were analyzed. Univariate analysis and principal component analysis (PCA) were performed.

Results

Family caregivers' experiences were divided into three domains by PCA: protect children from the patient's imminent death, little regard for the children, and worry and concern about the children's emotional reaction. Family caregivers' common experiences were as follows: "I wanted to know how the children felt," "I wanted to avoid making the children confused," and "I did not have much time to talk with and/or play with the children." About 30% of family caregivers reported that they "did not talk" about death and dying of patients to minor children. Spouses of patients and family caregivers who did not talk about death tended to experience distress and worry.

Conclusions

Most family caregivers experienced worry and fear regarding minor children's emotional reaction, therefore, clinicians need to explain children's emotional and psychological reaction to family caregivers when a patient is at the end-of-life.

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Efficacy and safety of taxane monotherapy in advanced gastric cancer refractory to triplet chemotherapy with docetaxel, cisplatin, and S-1: a multicenter retrospective study

Abstract

Purpose

Taxane monotherapy is widely used for advanced gastric cancer (AGC) after failure of standard first-line chemotherapy with fluoropyrimidine and cisplatin. Triplet chemotherapy with docetaxel, cisplatin, and S-1 (DCS) is a promising regimen for first-line chemotherapy of AGC. The aim of this study was to evaluate the efficacy of taxane monotherapy in patients refractory to DCS.

Methods

We retrospectively evaluated the efficacy and safety of taxane monotherapy in patients with AGC refractory to first-line therapy with DCS between January 2010 and April 2015. Selection criteria were as follows: ECOG PS of 0–2, treatment with taxane monotherapy in second-line or third-line therapy after failure of second-line irinotecan, absence of massive ascites, and adequate organ function.

Results

A total of 30 patients were included in this study. Of these, 15 patients received paclitaxel while another 15 received nanoparticle albumin-bound paclitaxel in either second- or third-line treatment. Median age for the second/third-line group was 64.0/62.0 (range 27–75/42–75); 14/13 (93.3/86.7%) had ECOG PS of 0 or 1. No patients achieved complete or partial response and stable disease was observed in 37.5/35.7% of the patients in the second/third line. Median progression-free survival and overall survival were 3.4 and 5.8 months in the second-line group, and 2.0 and 4.5 months in the third-line group, respectively. The incidences of any grade ≥3 adverse events in the second-line group and the third-line group were 60.0 and 33.3%, respectively. There was no treatment-related death.

Conclusions

Taxane monotherapy after DCS failure had acceptable toxicities but was ineffective in AGC patients.

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Transarterial chemoembolization combined with recombinant human adenovirus type 5 H101 prolongs overall survival of patients with intermediate to advanced hepatocellular carcinoma: a prognostic nomogram study

Patients with intermediate to advanced hepatocellular carcinoma (HCC) are most commonly treated with transarterial chemoembolization (TACE). Previous studies showed that TACE combined with recombinant human ad...

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Identification of a novel leukemic-specific splice variant of DNMT3B and its stability

Abstract

DNA methyltransferases make use of alternative splicing mechanism to generate various splice variants, but their role(s) in modulating DNA methylation patterns in the cells is unclear. Notably, DNMT3B alone contains nearly 40 different splice variants. In this study, we have identified a novel splice variant of DNMT3B, which lacks exon 7 and 10 from leukemic cell lines which we termed as DNMT3B9. The exon 7 codes for the major part of PWWP domain, and exon 10 inclusion serves as a pluripotent marker. By quantitative RT-PCR using exon–exon junction-specific primers, we showed higher level of DNMT3B9 transcripts in several leukemic cell lines. However, DNMT3B9 expression was less in other tested cancer cell lines indicating that DNMT3B9 might serve as a leukemic-specific biomarker. Surprisingly, endogenous protein for DNMT3B9 was not detected in leukemic cells suggesting the unidentified RNA-related function(s) for DNMT3B9. In addition, we showed that DNMT3B9 protein lacks PWWP domain is less stable compared to other DNMT3B variants which contain PWWP domain through computational predictions and by cycloheximide half-life experiment. Taken together, we demonstrated the existence of novel leukemic-specific splice variant of DNMT3B and provide the evidence for the role of PWWP domain in the stability of DNMT3B. The findings reported here have relevance in epigenetic therapy, which is aimed to target the DNMT3B in cancer cells.

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A mixed methods study to explore the supportive care needs of breast cancer survivors

Abstract

Background

Needs assessment is the essence of quality cancer survivorship care. The aim of this study was to explore the supportive care needs of breast cancer survivors (BCS) in the first five years post-treatment.

Methods

A mixed methods approach was employed. A quantitative study included a Supportive Care Needs Survey, which was completed by 250 BCS to identify the level of their needs for help. The quantitative data informed semi-structured qualitative interviews undertaken with 60 BCS to explore in details their post-treatment needs and experiences.

Results

32.4% and 16.8% reported 1 – 5 and ≥6 needs for help, respectively. The regression analyses revealed that women within two years post-treatment and with higher educational level had higher levels of Psychological and Health Care System/Information needs. The qualitative data revealed that "continuity of care" and "life style advice and self-management" as prominent survivorship concerns. It was shown that determination to continue normal life, social support, and feeling overwhelmed by information were all experienced as important influences on survivors' need for help.

Conclusions

Post-treatment needs vary with BCS characteristics and to the domains concerned. The approach to post-treatment care needs to be personalized and viable.

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Next-generation sequencing of cytologic preparations: An analysis of quality metrics

BACKGROUND

Next-generation sequencing (NGS) fails for many small biopsies (BXs) because of a low overall DNA concentration or tumor percentage. Cytology smears and liquid-based preparations (LBPs), or smears/LBPs, often contain abundant tumor cells and may provide adequate material for molecular testing when other materials are insufficient. This study examined the performance of smears/LBPs on a clinical NGS assay.

METHODS

This study retrospectively reviewed quality metrics from consecutive smear/LBP, core BX, and cell block (CB) cases run on a hybrid-capture NGS assay interrogating 309 cancer-related genes. The following quality metrics were compared: adequacy rate, initial DNA concentration, postshearing fragment size, post–library preparation fragment size, fragment size difference, insert size, total reads, passing-filter reads aligned, percent passing-filter unique reads aligned, mean target coverage, percentage of loci with >100× coverage, percent duplication rate, percent selected bases, and percent usable bases on bait.

RESULTS

Twenty-three of 26 smears/LBPs (88%) were successfully sequenced, whereas 77 of 87 core BXs (89%) and 29 of 30 CBs (97%) were. The mean target coverage, median insert size, and percent usable bases were significantly higher in the smear/LBP category. The postshearing fragment size and the percent duplication were significantly lower for smears/LBPs.

CONCLUSIONS

The adequacy rate of cytology smears/LBPs for NGS is comparable to that of core BXs or CBs. Increased values for the mean insert size, mean target coverage, and percent usable bases, along with a lower duplication rate, suggest that smears/LBPs provide higher quality DNA than formalin-fixed material. Cytology smears/LBPs can serve as a valuable source of material for molecular testing. Cancer (Cancer Cytopathol) 2017. © 2017 American Cancer Society.

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The pathogenesis, diagnosis, and management of metastatic tumors to the ovary: a comprehensive review

Abstract

Secondary tumors of the ovary account for 10–25% of all ovarian malignancies. The most common tumors that give rise to ovarian metastases include breast, colorectal, endometrial, stomach, and appendix cancer. The correct diagnosis of secondary ovarian tumors may be challenging as they are not infrequently misdiagnosed as primary ovarian cancer, particularly in the case of mucinous adenocarcinomas. The distinction from the latter is essential, as it requires different treatment. Immunohistochemistry plays an important role in distinguishing primary ovarian tumors from extra-ovarian metastases and, furthermore, may suggest the primary tumor site. Despite extensive study, some cases remain equivocal even after assessing a broad spectrum of antigens. Therefore, gene expression profiling represents an approach able to further discriminate equivocal findings, and one that has been proven effective in determining the origin of cancer of unknown primary site. The available data concerning secondary ovarian tumors is rather limited owing to the relative heterogeneity of this group and the practical absence of any prospective trials. However, several intriguing questions are encountered in daily practice, including rational diagnostic workup, the role of cytoreductive surgery, and consequent adjuvant chemotherapy. This review seeks to address these issues comprehensively and summarize current knowledge on the epidemiology, pathogenesis, and management of secondary ovarian tumors, including further discussion on the different pathways of metastatisation, metastatic organotropism, and their possible molecular mechanisms.

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Editorial: Childhood Cancer in sub-Saharan Africa

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National evaluation of multidisciplinary quality metrics for head and neck cancer

BACKGROUND

The National Quality Forum has endorsed quality-improvement measures for multiple cancer types that are being developed into actionable tools to improve cancer care. No nationally endorsed quality metrics currently exist for head and neck cancer.

METHODS

The authors identified patients with surgically treated, invasive, head and neck squamous cell carcinoma in the National Cancer Data Base from 2004 to 2014 and compared the rate of adherence to 5 different quality metrics and whether compliance with these quality metrics impacted overall survival. The metrics examined included negative surgical margins, neck dissection lymph node (LN) yield ≥ 18, appropriate adjuvant radiation, appropriate adjuvant chemoradiation, adjuvant therapy within 6 weeks, as well as overall quality.

RESULTS

In total, 76,853 eligible patients were identified. There was substantial variability in patient-level adherence, which was 80% for negative surgical margins, 73.1% for neck dissection LN yield, 69% for adjuvant radiation, 42.6% for adjuvant chemoradiation, and 44.5% for adjuvant therapy within 6 weeks. Risk-adjusted Cox proportional-hazard models indicated that all metrics were associated with a reduced risk of death: negative margins (hazard ratio [HR] 0.73; 95% confidence interval [CI], 0.71-0.76), LN yield ≥ 18 (HR, 0.93; 95% CI, 0.89-0.96), adjuvant radiation (HR, 0.67; 95% CI, 0.64-0.70), adjuvant chemoradiation (HR, 0.84; 95% CI, 0.79-0.88), and adjuvant therapy ≤6 weeks (HR, 0.92; 95% CI, 0.89-0.96). Patients who received high-quality care had a 19% reduced adjusted hazard of mortality (HR, 0.81; 95% CI, 0.79-0.83).

CONCLUSIONS

Five head and neck cancer quality metrics were identified that have substantial variability in adherence and meaningfully impact overall survival. These metrics are appropriate candidates for national adoption. Cancer 2017. © 2017 American Cancer Society.

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A multidimensional view of racial differences in access to prostate cancer care

BACKGROUND

Racial disparities in prostate cancer treatment and outcomes are widespread and poorly understood. In the current study, the authors sought to determine whether access to care, measured across multiple dimensions, contributed to racial differences in prostate cancer.

METHODS

The Philadelphia Area Prostate Cancer Access Study (P² Access) included 2374 men diagnosed with localized prostate cancer between 2012 and 2014. Men were surveyed to assess their experiences accessing care (response rate of 51.1%). The authors determined appointment availability at 151 urology practices using simulated patient telephone calls and calculated travel distances using geospatial techniques. Multivariable logistic regression models were used to determine the association between 5 different domains of access (availability, accessibility, accommodation, affordability, and acceptability) and receipt of treatment, perceived quality of care, and physician-patient communication.

RESULTS

There were 1907 non-Hispanic white and 394 black men in the study cohort. Overall, approximately 85% of the men received definitive treatment with no differences noted by race. Black men were less likely to report a high quality of care (69% vs 81%; P<.001) and good physician-patient communication (60% vs 71%; P<.001) compared with white men. In adjusted models, none of the 5 domains of access were found to be associated with definitive treatment overall or with radical prostatectomy. All access domains were associated with perceived quality of care and communication, although these domains did not mediate racial disparities.

CONCLUSIONS

To the authors' knowledge, the current study presents the first comprehensive assessment of prostate cancer care access, treatment, and patient experience, demonstrating that although access was related to overall perceived quality of care and better physician-patient communication, it did not appear to explain observed racial differences. Cancer 2017. © 2017 American Cancer Society.

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The role of medical/nursing skills training in caregiver confidence and burden: A CanCORS study

BACKGROUND

Informal cancer caregivers provide essential support to cancer patients, including performing direct medical/nursing tasks, assisting with activities of daily living, and offering social support. This study examined associations between the receipt of medical/nursing skills training and the caregiver burden as well as the mediation of caregiving confidence on this relationship in a sample of caregivers of lung and colorectal cancer patients.

METHODS

Caregivers who had been identified by cancer patients in the Cancer Care Outcomes Research and Surveillance consortium completed a questionnaire assessing the care provided, the type of medical/nursing skills training received, the burden (measured with the modified short-form Zarit Burden Interview), and the confidence in caring for their patient's physical needs. Regression models that had been adjusted for sociodemographic, caregiver, and care recipient characteristics assessed the relationship between training received and burden, and a mediation analysis assessed the role of confidence in this relationship.

RESULTS

Six hundred forty-one caregivers performed some type of medical/nursing task, with 59% (n = 377) reporting that they did not receive training for all the care provided. Caregivers reported moderate levels of burden (mean summary score, 32.07; standard deviation, 12.66; possible range, 14-70), and a lack of receipt of training was associated with greater levels of burden (b = 2.60; standard error, 0.98; P = .01). Confidence partially mediated the relation between training and burden (Sobel's t = 1.90; P = 0.03).

CONCLUSIONS

As the number of cancer patients and caregivers increases, understanding how best to reduce the caregiver burden is necessary. Skills training is a potential area for interventions, but research on how best to provide training for caregivers (ie, the content, mode of delivery, and timing) is needed. Cancer 2017. © 2017 American Cancer Society.

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Intraoperative ventilation and postoperative respiratory assistance

1A013C01

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Survival outcome of weak estrogen /progesterone receptor expression in Her2 negative breast cancer is similar to triple negative breast cancer

Publication date: Available online 19 July 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Guo-Shiou Liao, Ming-Shen Dai, Huan-Ming Hsu, Chi-Hong Chu, Zhi-Jie Hong, Chun-Yu Fu, Yu-Ching Chou, Tzu-Chuan Huang, Jyh-Cherng Yu
BackgroundRecent publications have suggested that human epidermal growth factor receptor 2 (HER2)-negative breast cancers with "weak" estrogen receptor (ER)/progesterone receptor (PR) expression levels by immunohistochemical (IHC) analysis were considered as the triple-negative (TN) subtype. This study aimed to evaluate the overall survival (OS), disease-free survival rates (DFS), and disease-specific survival (DSS) based on ER and PR expression levels into one of three groups, ER and PR <1%, ER and PR 1%-20%, and ER or PR >20% by hormone therapy.MethodsMedical records of 3353 breast cancer patients treated from 2006 to 2013 were retrospectively reviewed. Tumor characteristics, type of treatment, OS, DFS and DSS were evaluated among the three patient groups.ResultsRegarding OS, there were significant differences according to the received hormone therapy in the different groups: ER and PR <1% (P = 0.972), ER and PR 1%-20% (P = 0.264), and ER or PR >20% (P = 0.014). Regarding DFS and DSS, there were also significant differences in the different groups: ER and PR <1% (P = 0.611, 0.766), ER and PR 1%-20% (P = 0.847, 0.629), and ER or PR >20% (P = 0.031, 0.002).ConclusionsIn HER2 negative breast cancer patient with hormone therapy, ER and PR expression level of 1%-20% has similar survival outcome to the ER and PR expression level of <1% by IHC analysis.



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Post-treatment surveillance of thyroid cancer

Publication date: Available online 19 July 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Laura Y. Wang, Ian Ganly
An increased incidence of differentiated thyroid cancer (DTC) has resulted in an increased population of thyroid cancer survivors requiring ongoing disease surveillance. Our institution's risk-adapted surveillance strategy is based on a contemporary understanding of disease biology, guided by analysis of prognostic factors and balanced application of available surveillance modalities. The goal of this strategy is to detect recurrent disease early, identify patients who would benefit from further treatment and reduce over investigation of low risk patients. This article describes our center's risk-stratified approach to the postoperative surveillance of patients with differentiated thyroid cancer with reference to the recent 2015 American Thyroid Association management guidelines.



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Epithelioid sarcomas: how important is loco-regional control?

Publication date: Available online 19 July 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): A. Pradhan, R.J. Grimer, A. Abudu, R.M. Tillman, S.R. Carter, L. Jeys, P.C. Ferguson, A.M. Griffin, J.S. Wunder
AimsTo investigate the impact of the method of treatment on the oncological outcomes in patients with epithelioid sarcomas managed at two international specialty sarcoma centres.MethodsThe databases of two centres were used to identify patients treated for epithelioid sarcomas between 1985 to 2012. Patient, tumor, treatment and outcome data was collected.ResultsThere were 36 males and 18 females with a mean age of 38.3 years (range 9 to 79). Of 49 patients who were treated surgically, limb salvage surgery was carried out in 38 patients (78%) and limb amputation in 11 (22%). Of 49 total patients who underwent surgery for ES, 48 (98%) with ES had negative margin resection and 24 (49%) received (neo) adjuvant radiotherapy. Regional lymph node metastases developed in 5 (13%) patients. The five-year risk of local recurrence was 14%. The overall survival rate at five and ten years was 70% and 66% respectively. In multivariate analysis of patients with localized disease and negative margins, survival and risk of metastases was worse in those treated by amputation.ConclusionThis series has shown that although the rate of local recurrence is not influenced by the type of surgery, the risk of metastases is higher following amputation. This finding is likely due to patients with larger, deeper and more locally advanced tumors requiring amputation. However, we could not prove that immediate amputation was likely to affect overall survival.



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Risk of hospitalization among survivors of childhood and adolescent acute lymphoblastic leukemia compared to siblings and a general population sample

Publication date: August 2017
Source:Cancer Epidemiology, Volume 49
Author(s): Judy Y. Ou, Rochelle R. Smits-Seemann, Sapna Kaul, Mark N. Fluchel, Carol Sweeney, Anne C. Kirchhoff
BackgroundAcute Lymphoblastic Leukemia (ALL) has a high survival rate, but cancer-related late effects in the early post-treatment years need documentation. Hospitalizations are an indicator of the burden of late effects. We identify rates and risk factors for hospitalization from five to ten years after diagnosis for childhood and adolescent ALL survivors compared to siblings and a matched population sample.Methods176 ALL survivors were diagnosed at ≤22 years between 1998 and 2008 and treated at an Intermountain Healthcare facility. The Utah Population Database identified siblings, an age- and sex-matched sample of the Utah population, and statewide inpatient hospital discharges. Sex- and birth year-adjusted Poisson models with Generalized Estimating Equations and robust standard errors calculated rates and rate ratios. Cox proportional hazards models identified demographic and clinical risk factors for hospitalizations among survivors.ResultsHospitalization rates for survivors (Rate:3.76, 95% CI=2.22–6.36) were higher than siblings (Rate:2.69, 95% CI=1.01–7.18) and the population sample (Rate:1.87, 95% CI=1.13–3.09). Compared to siblings and population comparisons, rate ratios (RR) were significantly higher for survivors diagnosed between age 6 and 22 years (RR:2.87, 95% CI=1.03–7.97 vs siblings; RR:2.66, 95% CI=1.17–6.04 vs population comparisons). Rate ratios for diagnosis between 2004 and 2008 were significantly higher compared to the population sample (RR:4.29, 95% CI=1.49, 12.32), but not siblings (RR:2.73, 95% CI=0.54, 13.68). Survivors originally diagnosed with high-risk ALL did not have a significantly higher risk than siblings or population comparators. However, high-risk ALL survivors (Hazard ratio [HR]:3.36, 95% CI=1.33–8.45) and survivors diagnosed from 2004 to 2008 (HR:9.48, 95% CI=1.93–46.59) had the highest risk compared to their survivor counterparts.ConclusionsFive to ten years after diagnosis is a sensitive time period for hospitalizations in the ALL population. Survivors of childhood ALL require better long-term surveillance.



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Safety of Differential Radiation Dosing in Lymph Node Positive Necks treated with IMRT

Publication date: Available online 19 July 2017
Source:Practical Radiation Oncology
Author(s): Stephen Sozio, Zorimar Rivera-Núñez, Omar Mahmoud, Sung Kim
PurposeWhen treating Head and Neck Squamous Cell Carcinoma (HNSCC) with intensity modulated radiation therapy (IMRT), it is common to use several dose levels for a lymph node positive neck: full dose (66–70Gy) to gross cancer, intermediate dose (59–63Gy) to higher risk neck regions, and standard dose (50–54Gy) to lower risk neck regions. However, there is no consensus regarding how much of the neck should receive intermediate versus standard dose.Materials and MethodsHNSCC patients that were treated with IMRT were identified from two academic medical centers between 2004–2016. Intermediate dose was restricted to a region of the neck 2 cm margin above and below the most superior and inferior involved lymph nodes, and standard dose was delivered to more distal neck regions. Descriptive statistics were calculated for demographics and clinical characteristics as well as proportions for failures two years after treatment. Failure outside the intermediate dose region was determined by calculating confidence intervals from a modification of the Poisson distribution.ResultsOf the 57 necks included in this study, 17.5% experienced disease recurrence in the neck within 2years of completing treatment. All failures were within the 2 cm margin above or below the most superior and inferior involved nodes; there were no failures outside this 2cm margin (95%CI: 0%–7.7%).ConclusionsThe results of this study support the feasibility of treating only the neck adjacent to gross neck disease to an intermediate dose, and treating the remainder of the neck to a lower, standard dose. Though these results are encouraging, additional study of this treatment paradigm is warranted.



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Sexual Quality of Life Following Prostate Intensity Modulated Radiotherapy (IMRT) with a Rectal/Prostate Spacer: Secondary Analysis of a Phase III Trial

Publication date: Available online 19 July 2017
Source:Practical Radiation Oncology
Author(s): Daniel A Hamstra, Neil Mariados, John Sylvester, Dhiren Shah, Eric Gross, Richard Hudes, David Beyer, Steven Kurtzman, Jeffrey Bogart, R. Alex Hsi, Michael Kos, Rodney Ellis, Mark Logsdon, Shawn Zimberg, Kevin Forsythe, Hong Zhang, Edward Soffen, Patrick Francke, Constantine Mantz, Peter Rossi, Theodore DeWeese, Stephanie Daignault-Newton, Benjamin W Fischer-Valuck, Anupama Chundury, Hiram A. Gay, Walter Bosch, Jeff Michalski
A phase 3 trial was performed using an absorbable hydrogel (SpaceOAR System®) to provide space between the prostate and rectum for men receiving image-guided prostate IMRT. Based upon a secondary analysis the spacer reduced penile bulb dose, penile bulb doses was correlated with erectile dysfunction, and in those with adequate sexual QOL at baseline the use of Spacer was associated with clinically meaningful better sexual QOL and decreased erectile dysfunction.



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Dosimetric Predictors for Acute Esophagitis During Radiation Therapy for Lung Cancer - Results of a Large Statewide Observational Study

Publication date: Available online 19 July 2017
Source:Practical Radiation Oncology
Author(s): Peter Paximadis, Matthew Schipper, Martha Matuszak, Mary Feng, Shruti Jolly, Thomas Boike, Inga Grills, Larry Kestin, Benjamin Movsas, Kent Griffith, Gregory Gustafson, Jean Moran, Teamour Nurushev, Jeffrey Radawski, Lori Pierce, James Hayman
PurposeThe purpose of this study is to identify dosimetric variables that best predict for acute esophagitis in patients treated for locally advanced non-small cell lung cancer in a prospectively accrued state-wide consortium.Methods and MaterialsPatients receiving definitive radiation therapy for stage II-III NSCLC within the Michigan Radiation Oncology Quality Consortium (MROQC) were included in the analysis. DVH data were analyzed to determine dose metrics (V10, V20, V30, V40, V50, and V60), as well as maximum dose to 2cc (D2cc), mean dose (MD), and generalized equivalent uniform dose (gEUD). Logistic regression models were used to characterize the risk of toxicity as a function of dose and other covariates. The ability of each variable to predict esophagitis, individually or in a multivariate model, was quantified by ROC analysis.ResultsThere were 533 patients who met study criteria and were included; 437 (81.9%) developed any grade of esophagitis. Significant variables on univariate analysis for grade? 2 esophagitis were concurrent chemotherapy, V20, V30, V40, V50, V60, MD, D2cc, and gEUD. For grade? 3 esophagitis, the predictive variables were: V30, V40, V50, V60, MD, D2cc, and gEUD. In multivariable modeling, gEUD was the most significant predictor of both grade? 2 and grade? 3 esophagitis. When gEUD was excluded from the model, D2cc was selected as the most predictive variable for grade? 3 esophagitis. For an estimated risk of grade? 3 esophagitis of 5%, the threshold values for gEUD and D2cc were 59.3Gy and 68Gy, respectively.ConclusionsIn this study, we report the novel finding that generalized equivalent uniform dose and D2cc, rather than mean dose, were the most predictive dose metrics for severe esophagitis. To limit the estimated risk of grade? 3 esophagitis to <5%, thresholds of 59.3Gy and 68Gy were identified for gEUD and D2cc, respectively.



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Journal de Pharmacie Clinique

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

JOURNAL DE PHARMACIE CLINIQUE Volume 36, numéro 2, 2017 Retour sur la journée annuelle des internes en pharmacie Cette 2è journée scientifique placée sous le thème de l'Économie de la santé : « Le prix du médicament en France : enjeux thérapeutiques contre enjeux économiques ? ».   › Retrouvez l'article paru dans le Journal de Pharmacie CliniqueN°2-2017.

SOMMAIRE : ÉDITORIAL >  L'importance du réseautage !  Aude Desnoyer, Aurélie Guérin, André Rieutord SYNTHÈSES >  Formation et opportunités de carrières en pharmacie hospitalière : le point de vue de futurs et de jeunes diplômés du DES de pharmacie  Chloé Duran, Laura di Trapani, Christel Hosselet, Marie Lenski, Evariste Delande, Delphine Heurté, Alexandre Drezet, Jérémie Zerbit, Emmanuel Cirot, Clément Delage >  Comment le pharmacien peut-il prendre l'initiative pour coopérer avec les services cliniques ?  Marc Frachette, Véronique Zardet >  Votre temps-réponse est-il assez rapide ? Mise en œuvre d'un projet lean en pharmacie hospitalière afin de réduire le temps de préparation des ordonnances  Lise Vaillancourt, Mimi Truong >  Évaluation des technologies de santé en milieu hospitalier : organisations possibles et exemples appliqués aux dispositifs médicaux  Nicolas Martelli >  Accompagnement pharmaceutique du patient obèse à l'officine : état des lieux territorial  Audrey Decottignies, Sophie Renet, Sophie Cavalier, Guillaume Pourcher, André Rieutord CONGRÈS 2e Journée scientifique des internes en pharmacie d'Île-de-France  Aurélie Chaigneau, Rémi Pieragostini, Marie Cabagnols, Clément Delage

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Current Concepts on Hematopoietic Stem Cell Transplantation Outcome Registries; Emphases on Resource Requirements for New Registries

Publication date: Available online 19 July 2017
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Fazal Hussain, Naeem Chaudhri, Feras Alfraih, Mahmoud Aljurf
There is tremendous variability in size, scope, and resource requirements for registries depending on the number of patients and participating sites. The outcome registries are organized systems to collect uniform data using an observational study methodology. Patient registries are used to determine specified outcomes for a population for predetermined scientific, clinical, or policy purposes. Historically, outcome registries established in the development of hematopoietic stem cell transplantation (HSCT) have now evolved into myriads of locoregional and international transplant activity and outcome resources. Over time, these registries have contributed immensely in determining trends, patterns, and treatment outcomes in HSCT. There is wider variation in the goals, mission, objectives, and outcomes of the ongoing registries depending on the organizational structure. There is a growing trend toward overarching relationship of these registries to serve as complementary and interoperable resources for high potential collaborative research. In addition to capacity building, standardized, accredited, and optimally operational registries can provide unmatched and unparalleled research data that cannot be obtained otherwise. Moving forward, HSCT data collection, collation, and interpretation should be an integral part of the treatment rather than an option. Quality assurance and continuous quality improvement of the data are pivotal for credibility, measurable/quantifiable outcomes, clinically significant impact, and setting new benchmarks.



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