Breast cancer subtype and survival by parity and time since last birth

Abstract

Background

Pregnancy affects breast cancer risk but how it affects the subtype and prognosis remain controversial. We studied the effect of parity and time since last birth on breast cancer subtype and outcome.

Patients and methods

We conducted a retrospective multivariate cohort study including all premenopausal women with early breast cancer aged ≤ 50 years (N = 1306) at diagnosis at the University Hospitals Leuven (Jan. 2000–Dec. 2009). Primary study endpoints were the breast cancer subtype, disease-free survival, and distant disease-free survival by parity and time since last birth. Statistical methods used were baseline-category logits models and Cox proportional hazard models. Multivariable models were used to correct for possible confounders.

Results

Breast cancer subtypes did not differ between nulliparous (N = 266) and parous women (N = 1040) but subtypes differed significantly in parous women by time since last birth (p < 0.001). Tumors within 5 years of last birth were proportionally more likely triple negative and HER-2 like, even when corrected for age at diagnosis. After a mean follow-up period of 10 years, parous women had a better disease-free survival compared to nulliparous women (HR 0.733; CI 0.560–0.961; p = 0.025, HR 0.738; CI 0.559–0.974; p = 0.032 before and after correction for known prognostic factors, respectively). In parous women, a longer time since last birth was correlated with a longer disease-free survival compared to patients with a recent pregnancy (HR 0.976; CI 0.957–0.996; p = 0.018). However, after correction, this association completely disappeared (HR 1.010; CI 0.982–1.040; p = 0.480).

Conclusion

We observed a better disease-free survival for parous than nulliparous women. The influence of recent birth on disease-free survival is probably due to tumor and patient characteristics, as recent birth is associated with more aggressive subtypes.

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Measuring Development of Adolescent and Young Adult Cancer Patients: An Integrative Review of Available Instruments

Journal of Adolescent and Young Adult Oncology , Vol. 0, No. 0.


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Measuring Development of Adolescent and Young Adult Cancer Patients: An Integrative Review of Available Instruments

Journal of Adolescent and Young Adult Oncology , Vol. 0, No. 0.


http://ift.tt/2H3mP0x

The challenges of fertility preservation in cancer patients: an interview with Michael Grynberg

Future Oncology, Ahead of Print.


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FORWARD I: a Phase III study of mirvetuximab soravtansine versus chemotherapy in platinum-resistant ovarian cancer

Future Oncology, Ahead of Print.


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Hydration requirements with emetogenic chemotherapy: granisetron extended-release subcutaneous versus palonosetron

Future Oncology, Ahead of Print.


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A multiparametric analysis combining DCE-MRI- and IVIM -derived parameters to improve differentiation of parotid tumors: a pilot study

Future Oncology, Ahead of Print.


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The challenges of fertility preservation in cancer patients: an interview with Michael Grynberg

Future Oncology, Ahead of Print.


http://ift.tt/2Ef0qQ2

FORWARD I: a Phase III study of mirvetuximab soravtansine versus chemotherapy in platinum-resistant ovarian cancer

Future Oncology, Ahead of Print.


http://ift.tt/2CaEJe1

Hydration requirements with emetogenic chemotherapy: granisetron extended-release subcutaneous versus palonosetron

Future Oncology, Ahead of Print.


http://ift.tt/2EhhtAS

A multiparametric analysis combining DCE-MRI- and IVIM -derived parameters to improve differentiation of parotid tumors: a pilot study

Future Oncology, Ahead of Print.


http://ift.tt/2CaWzOa

Platelets enhance Multiple Myeloma progression via IL-1{beta} upregulation

Purpose: Tumor cell-platelet interactions contribute to tumor progression and metastasis in solid tumors. However, the role of platelets in hematological malignancies is not clear. We investigated the association of platelet activation status with clinical stages in multiple myeloma (MM) patients and explored the role of platelets in MM progression. Experimental Design: Platelets were obtained from healthy donors and MM patients. We examined platelet activation status in MM patients by flow cytometry and transmission electron microscopy. We also observed the enriched pathways that are involved with platelet activation in RNA sequencing of platelets. MM cell lines were used to assess the effect of platelets on MM cell proliferation in vitro and their engraftment in vivo. RNA sequencing of MM cell lines was performed to explore molecular mechanisms underlying MM cell-platelet interaction and a CRISPR/Cas9 knockout approach was used for validation. Results: Platelets from MM patients were highly activated with disease progression. RNA sequencing of platelets revealed that genes involved in platelets were enriched in patients with smoldering MM (SMM) or MM. Platelets promoted MM cell proliferation in vitro and contributed to tumor engraftment in bone marrow in vivo. RNA sequencing revealed that IL-1β was upregulated in MM cell lines co-cultured with platelets, whereas IL-1β knockout in MM cell lines abrogated the effects of platelets on MM cell proliferation and engraftment in vivo. Conclusions: Platelets from MM patients were highly activated with disease progression. IL-1β is critical to platelet-mediated MM progression and might be a potential target for MM treatment.

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Pan-cancer molecular classes transcending tumor lineage across 32 cancer types, multiple data platforms, and over 10,000 cases

Purpose: The Cancer Genome Atlas data resources represent an opportunity to explore commonalities across cancer types involving multiple molecular levels, but tumor lineage and histology can represent a barrier in moving beyond differences related to cancer type. Experimental Design: On the basis of gene expression data, we classified 10224 cancers, representing 32 major types, into ten molecular-based "classes."  Molecular patterns representing tissue or histologic dominant effects were first removed computationally, with the resulting classes representing emergent themes across tumor lineages. Results: Key differences involving mRNAs, miRNAs, proteins, and DNA methylation underscored the pan-cancer classes. One class expressing neuroendocrine and cancer-testis antigen markers represented ~4% of cancers surveyed. Basal-like breast cancers segregated into an exclusive class, distinct from all other cancers. Immune checkpoint pathway markers and molecular signatures of immune infiltrates were most strongly manifested within a class representing ~13% of cancers. Pathway-level differences involving hypoxia, NRF2-ARE, Wnt, and Notch were manifested in two additional classes enriched for mesenchymal markers and miR-200 silencing. Conclusions: All pan-cancer molecular classes uncovered here, with the important exception of the basal-like breast cancer class, involve a wide range of cancer types and would facilitate understanding the molecular underpinnings of cancers beyond tissue-oriented domains. Numerous biological processes associated with cancer in the laboratory setting were found here to be coordinately manifested across large subsets of human cancers. The number of cancers manifesting features of neuroendocrine tumors may be much higher than previously thought, which disease is known to occur in many different tissues.

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Ponatinib shows potent antitumor activity in small cell carcinoma of the ovary hypercalcemic type (SCCOHT) through multi-kinase inhibition

Purpose: Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare, aggressive ovarian cancer in young women that is universally driven by loss of the SWI/SNF ATPase subunits SMARCA4 and SMARCA2. A great need exists for effective targeted therapies for SCCOHT. Experimental Design: To identify underlying therapeutic vulnerabilities in SCCOHT, we conducted high-throughput siRNA and drug screens. Complementary proteomics approaches profiled kinases inhibited by ponatinib. Ponatinib was tested for efficacy in two patient-derived xenograft (PDX) models and one cell line xenograft model of SCCOHT. Results: The receptor tyrosine kinase (RTK) family was enriched in siRNA screen hits with FGFRs and PDGFRs being overlapping hits between drug and siRNA screens. Of multiple potent drug classes in SCCOHT cell lines, RTK inhibitors were only one of two classes with selectivity in SCCOHT relative to three SWI/SNF-wild-type ovarian cancer cell lines. We further identified ponatinib as the most effective clinically approved RTK inhibitor. Re-expression of SMARCA4 was shown to confer a 1.7-fold increase in resistance to ponatinib. Subsequent proteomic assessment of ponatinib target modulation in SCCOHT cell models confirmed inhibition of nine known ponatinib target kinases alongside 77 non-canonical ponatinib targets in SCCOHT. Finally, ponatinib delayed tumor doubling time four-fold in SCCOHT-1 xenografts while reducing final tumor volumes in SCCOHT PDX models by 58.6% and 42.5%. Conclusion: Ponatinib is an effective agent for SMARCA4-mutant SCCOHT in both in vitro and in vivo preclinical models through its inhibition of multiple kinases. Clinical investigation of this FDA-approved oncology drug in SCCOHT is warranted.

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Targeting HSF1: a prime integrator of proteotoxic stress response in myeloma

The HSF1 transcription factor is an integrator of the cellular stress response and its expression has demonstrated poor prognosis in multiple myeloma. Novel anti-HSF1 small molecule inhibitors CCT251236 and KRIB11 demonstrate in vitro and in vivo anti-myeloma activity, representing a novel approach for targeting the heat shock response in myeloma.

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Platelets enhance Multiple Myeloma progression via IL-1{beta} upregulation

Purpose: Tumor cell-platelet interactions contribute to tumor progression and metastasis in solid tumors. However, the role of platelets in hematological malignancies is not clear. We investigated the association of platelet activation status with clinical stages in multiple myeloma (MM) patients and explored the role of platelets in MM progression. Experimental Design: Platelets were obtained from healthy donors and MM patients. We examined platelet activation status in MM patients by flow cytometry and transmission electron microscopy. We also observed the enriched pathways that are involved with platelet activation in RNA sequencing of platelets. MM cell lines were used to assess the effect of platelets on MM cell proliferation in vitro and their engraftment in vivo. RNA sequencing of MM cell lines was performed to explore molecular mechanisms underlying MM cell-platelet interaction and a CRISPR/Cas9 knockout approach was used for validation. Results: Platelets from MM patients were highly activated with disease progression. RNA sequencing of platelets revealed that genes involved in platelets were enriched in patients with smoldering MM (SMM) or MM. Platelets promoted MM cell proliferation in vitro and contributed to tumor engraftment in bone marrow in vivo. RNA sequencing revealed that IL-1β was upregulated in MM cell lines co-cultured with platelets, whereas IL-1β knockout in MM cell lines abrogated the effects of platelets on MM cell proliferation and engraftment in vivo. Conclusions: Platelets from MM patients were highly activated with disease progression. IL-1β is critical to platelet-mediated MM progression and might be a potential target for MM treatment.

http://ift.tt/2Evlb9l

Pan-cancer molecular classes transcending tumor lineage across 32 cancer types, multiple data platforms, and over 10,000 cases

Purpose: The Cancer Genome Atlas data resources represent an opportunity to explore commonalities across cancer types involving multiple molecular levels, but tumor lineage and histology can represent a barrier in moving beyond differences related to cancer type. Experimental Design: On the basis of gene expression data, we classified 10224 cancers, representing 32 major types, into ten molecular-based "classes."  Molecular patterns representing tissue or histologic dominant effects were first removed computationally, with the resulting classes representing emergent themes across tumor lineages. Results: Key differences involving mRNAs, miRNAs, proteins, and DNA methylation underscored the pan-cancer classes. One class expressing neuroendocrine and cancer-testis antigen markers represented ~4% of cancers surveyed. Basal-like breast cancers segregated into an exclusive class, distinct from all other cancers. Immune checkpoint pathway markers and molecular signatures of immune infiltrates were most strongly manifested within a class representing ~13% of cancers. Pathway-level differences involving hypoxia, NRF2-ARE, Wnt, and Notch were manifested in two additional classes enriched for mesenchymal markers and miR-200 silencing. Conclusions: All pan-cancer molecular classes uncovered here, with the important exception of the basal-like breast cancer class, involve a wide range of cancer types and would facilitate understanding the molecular underpinnings of cancers beyond tissue-oriented domains. Numerous biological processes associated with cancer in the laboratory setting were found here to be coordinately manifested across large subsets of human cancers. The number of cancers manifesting features of neuroendocrine tumors may be much higher than previously thought, which disease is known to occur in many different tissues.

http://ift.tt/2sfQhwM

Ponatinib shows potent antitumor activity in small cell carcinoma of the ovary hypercalcemic type (SCCOHT) through multi-kinase inhibition

Purpose: Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare, aggressive ovarian cancer in young women that is universally driven by loss of the SWI/SNF ATPase subunits SMARCA4 and SMARCA2. A great need exists for effective targeted therapies for SCCOHT. Experimental Design: To identify underlying therapeutic vulnerabilities in SCCOHT, we conducted high-throughput siRNA and drug screens. Complementary proteomics approaches profiled kinases inhibited by ponatinib. Ponatinib was tested for efficacy in two patient-derived xenograft (PDX) models and one cell line xenograft model of SCCOHT. Results: The receptor tyrosine kinase (RTK) family was enriched in siRNA screen hits with FGFRs and PDGFRs being overlapping hits between drug and siRNA screens. Of multiple potent drug classes in SCCOHT cell lines, RTK inhibitors were only one of two classes with selectivity in SCCOHT relative to three SWI/SNF-wild-type ovarian cancer cell lines. We further identified ponatinib as the most effective clinically approved RTK inhibitor. Re-expression of SMARCA4 was shown to confer a 1.7-fold increase in resistance to ponatinib. Subsequent proteomic assessment of ponatinib target modulation in SCCOHT cell models confirmed inhibition of nine known ponatinib target kinases alongside 77 non-canonical ponatinib targets in SCCOHT. Finally, ponatinib delayed tumor doubling time four-fold in SCCOHT-1 xenografts while reducing final tumor volumes in SCCOHT PDX models by 58.6% and 42.5%. Conclusion: Ponatinib is an effective agent for SMARCA4-mutant SCCOHT in both in vitro and in vivo preclinical models through its inhibition of multiple kinases. Clinical investigation of this FDA-approved oncology drug in SCCOHT is warranted.

http://ift.tt/2EyTwEH

Targeting HSF1: a prime integrator of proteotoxic stress response in myeloma

The HSF1 transcription factor is an integrator of the cellular stress response and its expression has demonstrated poor prognosis in multiple myeloma. Novel anti-HSF1 small molecule inhibitors CCT251236 and KRIB11 demonstrate in vitro and in vivo anti-myeloma activity, representing a novel approach for targeting the heat shock response in myeloma.

http://ift.tt/2simVhv

Skeletal Muscle Quality Beyond Average Muscle Attenuation: A Proposal of Skeletal Muscle Phenotypes to Predict Short-Term Survival in Patients With Endometrial Cancer

Background: Increasing evidence links sarcopenia and cancer prognosis, but limited data have focused on whether and to what extent muscle radiodensity can impact cancer outcomes. This study was conducted to investigate whether skeletal muscle mass, when divided into subranges of low or high radiodensity, improves prediction of short-term survival in patients with endometrial cancer (EC). Four skeletal muscle phenotypes were proposed to assess which is the best predictor of 1-year mortality. Methods: Patients with EC who had CT images available within 30 days before treatment (n=208) were enrolled in a retrospective cohort. CT images at the third lumbar vertebra (L3) were used to assess overall skeletal muscle index (SMI), which was then divided into subranges of radiation attenuation: low- and high-radiodensity SMI. The average muscle radiation attenuation (AMA) was also assessed. SMI and AMA were categorized as below or above the median and as below or above 30 Hounsfield units (HU), respectively, to construct 4 skeletal muscle phenotypes: "high SMI + high AMA"; "low SMI + high AMA"; "high SMI + low AMA"; and "low SMI + low AMA". One-year survival was evaluated using the Kaplan-Meier method and Cox multiple regression analysis. Results: All of the skeletal muscle parameters, except the SMI, were significantly associated with shorter 1-year survival. The skeletal muscle phenotype of "low SMI + low AMA" showed the strongest association with 1-year mortality (hazard ratio, 5.36; 95% CI, 1.70–16.51). Conclusions: The additional value of classifying the skeletal muscle into subranges of radiodensity should be explored in the future. Evaluating the impact of skeletal muscle phenotypes on cancer prognosis is promising and must be assessed in further studies.

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NCCN News

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Uterine Neoplasms, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology

Endometrial carcinoma is a malignant epithelial tumor that forms in the inner lining, or endometrium, of the uterus. Endometrial carcinoma is the most common gynecologic malignancy. Approximately two-thirds of endometrial carcinoma cases are diagnosed with disease confined to the uterus. The complete NCCN Guidelines for Uterine Neoplasms provide recommendations for the diagnosis, evaluation, and treatment of endometrial cancer and uterine sarcoma. This manuscript discusses guiding principles for the diagnosis, staging, and treatment of early-stage endometrial carcinoma as well as evidence for these recommendations.

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Oncology Research Program

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Extending Our Reach--Will Telemedicine Get Us There?

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Secondary Neoplasms of the Female Lower Genital Tract After Hematopoietic Cell Transplantation

Hematopoietic cell transplantation (HCT) results in long-term survival (≥10 years) in 85% of patients who survive transplant-related complications within the first 2 years posttransplant. Transplant survivors, however, are at an increased risk of chronic health conditions compared with the general population, including the emergence of secondary malignant neoplasms. In particular, female transplant survivors may face a greater risk of lower genital tract (cervical, vulvar, or vaginal) neoplasms due to chronic immune dysregulation in the peritransplant and posttransplant environment. Persistent immune suppression may facilitate the carcinogenesis of human papillomavirus (HPV), the causative agent of nearly all cervical cancers and most vulvar and vaginal cancers. Nevertheless, the risk of these cancers has not been sufficiently quantified in female transplant survivors. Small clinical studies have shown that the rate of cervical cytological abnormalities increases after allogeneic HCT, but large population-based studies have not consistently demonstrated an increased risk of secondary cervical cancer after transplant compared with the general population; the risk of developing secondary vulvar or vaginal cancer after transplant remains unclear. A better understanding of the natural history of HPV-associated lower genital tract neoplasms and their transplant-related risk factors would help delineate optimal long-term follow-up protocols in this population. In this systematic review, we summarize the current literature on this topic and discuss the implications for cervical cancer screening and vaccination in female transplant recipients.

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Letter to the Editor: Chicken Noodle Soup (Capsule) for the Soul?

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The AJCC 8th Edition Staging System for Soft Tissue Sarcoma of the Extremities or Trunk: A Cohort Study of the SEER Database

Background: The AJCC recently published the 8th edition of its cancer staging system. Significant changes were made to the staging algorithm for soft tissue sarcoma (STS) of the extremities or trunk, including the addition of 2 additional T (size) classifications in lieu of tumor depth and grouping lymph node metastasis (LNM) with distant metastasis as stage IV disease. Whether these changes improve staging system performance is questionable. Patients and Methods: This retrospective cohort analysis of 21,396 adult patients with STS of the extremity or trunk in the SEER database compares the AJCC 8th edition staging system with the 7th edition and a newly proposed staging algorithm using a variety of statistical techniques. The effect of tumor size on disease-specific survival was assessed by flexible, nonlinear Cox proportional hazard regression using restricted cubic splines and fractional polynomials. Results: The slope of covariate-adjusted log hazards for sarcoma-specific survival decreases for tumors >8 cm in greatest dimension, limiting prognostic information contributed by the new T4 classification in the AJCC 8th edition. Anatomic depth independently provides significant prognostic information. LNM is not equivalent to distant, non-nodal metastasis. Based on these findings, an alternative staging system is proposed and demonstrated to outperform both AJCC staging schemes. The analyses presented also disclose no evidence of improved clinical performance of the 8th edition compared with the previous edition. Conclusions: The AJCC 8th edition staging system for STS is no better than the previous 7th edition. Instead, a proposed staging system based on histologic grade, tumor size, and anatomic depth shows significantly higher predictive accuracy, with higher model concordance than either AJCC staging system. Changes to existing staging systems should improve the performance of prognostic models. Until such improvements are documented, AJCC committees should refrain from modifying established staging schemes.

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Inflammatory Myofibroblastic Tumor Driven by Novel NUMA1-ALK Fusion Responds to ALK Inhibition

Inflammatory myofibroblastic tumors (IMTs) are soft tissue neoplasms with rare metastatic potential. Approximately half of IMTs are positive for an ALK rearrangement, and ALK inhibitors have been used successfully in the treatment of IMTs with a variety of ALK fusions. This report describes a 21-year-old woman with an aggressive, metastatic IMT with a novel NUMA1-ALK fusion that showed a dramatic response to the ALK inhibitors crizotinib and alectinib. To our knowledge, this report provides the first published description of an IMT with a NUMA1-ALK fusion. The patient's aggressive IMT responded favorably to crizotinib and alectinib, suggesting that ALK inhibitors may be effective in IMT with NUMA1-ALK fusions. We review published reports of ALK-driven IMTs that have received ALK inhibitor therapy and suggest characteristics that may be associated with favorable response to treatment. We also discuss the strengths and limitations of immunohistochemistry, fluorescence in situ hybridization, and next-generation sequencing in the diagnosis and management of IMTs.

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Real-World Impact of a Decision Support Tool on Colony-Stimulating Factor Use and Chemotherapy-Induced Febrile Neutropenia Among Patients With Breast Cancer

Background: White blood cell colony-stimulating factors (CSFs) decrease the incidence of chemotherapy-induced febrile neutropenia (FN). Widespread use of CSFs that is not guideline-concordant has been reported. Among patients with breast cancer receiving chemotherapy, the ability of evidence-based decision support tools to promote risk-appropriate reductions in CSF use without increased incidence of FN has not been examined. Methods: A retrospective cohort design and US commercial claims data were used. The impact of CSF decision support was analyzed among women with breast cancer receiving first-cycle chemotherapy from April 1, 2013, to March 30, 2015. The tool was implemented as part of a prior authorization process in 9 states starting July 1, 2014. Patients were assigned to intervention (ie, states where the decision support tool had been implemented) or nonintervention states (ie, 39 states where the tool had not been implemented). CSF use and subsequent incidence of FN were compared using difference-in-difference (DID) regressions adjusting for baseline differences in FN risk factors such as comorbidities and various infections. Results: The study sample of 7,224 patients (intervention states: pre-implementation, 1,991 and post-implementation, 2,010; nonintervention states: pre-implementation, 1,569 and post-implementation, 1,654) showed no significant difference in risk factors. Before and after implementation, a significant decrease in the proportion of patients with CSF use was observed in the intervention states (75% to 69%) compared with no significant change in the nonintervention (72% to 71%) states (DID, –5.4%; 95% CI, –6.0% to –4.7%; P=.006). No significance increase in FN incidence occurred in intervention (5.0% to 5.5%) and nonintervention (5.4% to 4.8%) states (DID, 0.2%; 95% CI, –0.20 to 0.30; P=.78). Similar results were obtained in subgroups by comorbidities and in sensitivity analyses by claims-based FN definitions. Conclusions: CSF use decreased modestly after implementation of the decision support tool, with no observed changes in FN rates. Such tools can reduce practice variation to improve care standards.

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NCCN Guidelines Insights: T-Cell Lymphomas, Version 2.2018

Natural killer (NK)/T-cell lymphomas are a rare and distinct subtype of non-Hodgkin's lymphomas. NK/T-cell lymphomas are predominantly extranodal and most of these are nasal type, often localized to the upper aerodigestive tract. Because extranodal NK/T-cell lymphomas (ENKL) are rare malignancies, randomized trials comparing different regimens have not been conducted to date and standard therapy has not yet been established for these patients. These NCCN Guidelines Insights discuss the recommendations for the diagnosis and management of patients with ENKL as outlined in the NCCN Guidelines for T-Cell Lymphomas.

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Evolving Roles of Histologic Evaluation and Molecular/Genomic Profiling in the Management of Endometrial Cancer

Endometrial cancers are the most common gynecologic malignancies. The staging of endometrial cancer has evolved from a clinical-based system to a comprehensive surgical-pathologic approach that allows for better risk stratification and treatment planning. Over the past few years, use of NCCN's sentinel lymph node (SLN) mapping algorithm for the surgical staging of endometrial cancer has gained significant acceptance and is now commonly applied in many practices. However, pathologic evaluation of prognostic factors is beset by challenges, including the reproducibility of histologic classification and FIGO's grading, as well as the questionable clinical significance of low-volume tumor in SLNs. With the revelation of major genomic classes of endometrial cancer comes the potential for improved, reproducible, and prognostically relevant classification schemes, which integrate traditional pathologic parameters with genomic findings, to aid in treatment decisions. Pathologic identification of new variants of endometrial cancer, such as undifferentiated carcinoma, continues to advance the phenotypic spectrum of these tumors, spurring genomic and functional studies to further characterize their mechanistic underpinnings and potentially reveal new avenues for treatment. In the era of precision medicine, pathologic assessment of biomarkers (eg, mismatch repair proteins) and recognition of phenotypes that are amenable to specific targeted therapies (such as POLE-mutated tumors) have become integral to the management of women with endometrial carcinoma.

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Description of Venous Thromboembolism in Hospitalized Patients With Metastatic Cancer: A National Sample

Background: This study aimed to determine patient-, tumor-, and hospital-level characteristics associated with venous thromboembolism (VTE), and to assess the impact of VTE on in-hospital mortality and length of hospital stay in hospitalized patients with metastatic cancer. Methods: Using the Nationwide Inpatient Sample database, a cross-sectional analysis was performed of patients aged ≥18 years with at least 1 diagnosis of primary solid tumor and subsequent secondary or metastatic tumor between 2008 and 2013. Results: Among 850,570 patients with metastatic cancer, 6.6% were diagnosed with VTE. A significant trend for increasing VTE rates were observed from 2008 to 2013 (5.7%–7.2%; P<.0001). Using an adjusted multilevel hierarchical regression model, higher odds of VTE were seen among women (odds ratio [OR], 1.04; 95% CI, 1.02–1.06), black versus white patients (OR, 1.14; 95% CI, 1.11–1.18), and those with an Elixhauser comorbidity index score of ≥3 (OR, 2.50; 95% CI, 2.38–2.63). Hospital-level correlates of VTE included treatment in a teaching hospital (OR, 1.05; 95% CI, 1.01–1.11) and an urban location (OR, 1.18; 95% CI, 1.09–1.27), and admission to hospitals in the Northeast (OR, 1.16; 95% CI, 1.08–1.24) and West (OR, 1.09; 95% CI, 1.03–1.16) versus the South. Patients with metastasis to the liver, brain, or respiratory organs and those with multiple (≥2) metastatic sites had higher odds of VTE, whereas those with metastasis to lymph nodes and genital organs had lower odds. Patients diagnosed with versus without VTE had higher odds of in-hospital mortality (OR, 1.50; 95% CI, 1.38–1.63) and prolonged hospital stay (OR, 1.65; 95% CI, 1.57–1.73). Conclusions: The frequency of VTE in patients with metastatic cancer is increasing. Patient characteristics, hospital factors, and site of metastasis independently predict the occurrence of VTE and allow for better stratification of patients with cancer according to their VTE risk.

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In Memoriam: Jimmie C. Holland, MD (1928-2017)

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NCCN News

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Uterine Neoplasms, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology

Endometrial carcinoma is a malignant epithelial tumor that forms in the inner lining, or endometrium, of the uterus. Endometrial carcinoma is the most common gynecologic malignancy. Approximately two-thirds of endometrial carcinoma cases are diagnosed with disease confined to the uterus. The complete NCCN Guidelines for Uterine Neoplasms provide recommendations for the diagnosis, evaluation, and treatment of endometrial cancer and uterine sarcoma. This manuscript discusses guiding principles for the diagnosis, staging, and treatment of early-stage endometrial carcinoma as well as evidence for these recommendations.

http://ift.tt/2EyQX5x

Oncology Research Program

http://ift.tt/2snmjXU

Skeletal Muscle Quality Beyond Average Muscle Attenuation: A Proposal of Skeletal Muscle Phenotypes to Predict Short-Term Survival in Patients With Endometrial Cancer

Background: Increasing evidence links sarcopenia and cancer prognosis, but limited data have focused on whether and to what extent muscle radiodensity can impact cancer outcomes. This study was conducted to investigate whether skeletal muscle mass, when divided into subranges of low or high radiodensity, improves prediction of short-term survival in patients with endometrial cancer (EC). Four skeletal muscle phenotypes were proposed to assess which is the best predictor of 1-year mortality. Methods: Patients with EC who had CT images available within 30 days before treatment (n=208) were enrolled in a retrospective cohort. CT images at the third lumbar vertebra (L3) were used to assess overall skeletal muscle index (SMI), which was then divided into subranges of radiation attenuation: low- and high-radiodensity SMI. The average muscle radiation attenuation (AMA) was also assessed. SMI and AMA were categorized as below or above the median and as below or above 30 Hounsfield units (HU), respectively, to construct 4 skeletal muscle phenotypes: "high SMI + high AMA"; "low SMI + high AMA"; "high SMI + low AMA"; and "low SMI + low AMA". One-year survival was evaluated using the Kaplan-Meier method and Cox multiple regression analysis. Results: All of the skeletal muscle parameters, except the SMI, were significantly associated with shorter 1-year survival. The skeletal muscle phenotype of "low SMI + low AMA" showed the strongest association with 1-year mortality (hazard ratio, 5.36; 95% CI, 1.70–16.51). Conclusions: The additional value of classifying the skeletal muscle into subranges of radiodensity should be explored in the future. Evaluating the impact of skeletal muscle phenotypes on cancer prognosis is promising and must be assessed in further studies.

http://ift.tt/2EszBav

Extending Our Reach--Will Telemedicine Get Us There?

http://ift.tt/2sjlXBz

Secondary Neoplasms of the Female Lower Genital Tract After Hematopoietic Cell Transplantation

Hematopoietic cell transplantation (HCT) results in long-term survival (≥10 years) in 85% of patients who survive transplant-related complications within the first 2 years posttransplant. Transplant survivors, however, are at an increased risk of chronic health conditions compared with the general population, including the emergence of secondary malignant neoplasms. In particular, female transplant survivors may face a greater risk of lower genital tract (cervical, vulvar, or vaginal) neoplasms due to chronic immune dysregulation in the peritransplant and posttransplant environment. Persistent immune suppression may facilitate the carcinogenesis of human papillomavirus (HPV), the causative agent of nearly all cervical cancers and most vulvar and vaginal cancers. Nevertheless, the risk of these cancers has not been sufficiently quantified in female transplant survivors. Small clinical studies have shown that the rate of cervical cytological abnormalities increases after allogeneic HCT, but large population-based studies have not consistently demonstrated an increased risk of secondary cervical cancer after transplant compared with the general population; the risk of developing secondary vulvar or vaginal cancer after transplant remains unclear. A better understanding of the natural history of HPV-associated lower genital tract neoplasms and their transplant-related risk factors would help delineate optimal long-term follow-up protocols in this population. In this systematic review, we summarize the current literature on this topic and discuss the implications for cervical cancer screening and vaccination in female transplant recipients.

http://ift.tt/2EzeYtn

Letter to the Editor: Chicken Noodle Soup (Capsule) for the Soul?

http://ift.tt/2siMKy3

The AJCC 8th Edition Staging System for Soft Tissue Sarcoma of the Extremities or Trunk: A Cohort Study of the SEER Database

Background: The AJCC recently published the 8th edition of its cancer staging system. Significant changes were made to the staging algorithm for soft tissue sarcoma (STS) of the extremities or trunk, including the addition of 2 additional T (size) classifications in lieu of tumor depth and grouping lymph node metastasis (LNM) with distant metastasis as stage IV disease. Whether these changes improve staging system performance is questionable. Patients and Methods: This retrospective cohort analysis of 21,396 adult patients with STS of the extremity or trunk in the SEER database compares the AJCC 8th edition staging system with the 7th edition and a newly proposed staging algorithm using a variety of statistical techniques. The effect of tumor size on disease-specific survival was assessed by flexible, nonlinear Cox proportional hazard regression using restricted cubic splines and fractional polynomials. Results: The slope of covariate-adjusted log hazards for sarcoma-specific survival decreases for tumors >8 cm in greatest dimension, limiting prognostic information contributed by the new T4 classification in the AJCC 8th edition. Anatomic depth independently provides significant prognostic information. LNM is not equivalent to distant, non-nodal metastasis. Based on these findings, an alternative staging system is proposed and demonstrated to outperform both AJCC staging schemes. The analyses presented also disclose no evidence of improved clinical performance of the 8th edition compared with the previous edition. Conclusions: The AJCC 8th edition staging system for STS is no better than the previous 7th edition. Instead, a proposed staging system based on histologic grade, tumor size, and anatomic depth shows significantly higher predictive accuracy, with higher model concordance than either AJCC staging system. Changes to existing staging systems should improve the performance of prognostic models. Until such improvements are documented, AJCC committees should refrain from modifying established staging schemes.

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Inflammatory Myofibroblastic Tumor Driven by Novel NUMA1-ALK Fusion Responds to ALK Inhibition

Inflammatory myofibroblastic tumors (IMTs) are soft tissue neoplasms with rare metastatic potential. Approximately half of IMTs are positive for an ALK rearrangement, and ALK inhibitors have been used successfully in the treatment of IMTs with a variety of ALK fusions. This report describes a 21-year-old woman with an aggressive, metastatic IMT with a novel NUMA1-ALK fusion that showed a dramatic response to the ALK inhibitors crizotinib and alectinib. To our knowledge, this report provides the first published description of an IMT with a NUMA1-ALK fusion. The patient's aggressive IMT responded favorably to crizotinib and alectinib, suggesting that ALK inhibitors may be effective in IMT with NUMA1-ALK fusions. We review published reports of ALK-driven IMTs that have received ALK inhibitor therapy and suggest characteristics that may be associated with favorable response to treatment. We also discuss the strengths and limitations of immunohistochemistry, fluorescence in situ hybridization, and next-generation sequencing in the diagnosis and management of IMTs.

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Real-World Impact of a Decision Support Tool on Colony-Stimulating Factor Use and Chemotherapy-Induced Febrile Neutropenia Among Patients With Breast Cancer

Background: White blood cell colony-stimulating factors (CSFs) decrease the incidence of chemotherapy-induced febrile neutropenia (FN). Widespread use of CSFs that is not guideline-concordant has been reported. Among patients with breast cancer receiving chemotherapy, the ability of evidence-based decision support tools to promote risk-appropriate reductions in CSF use without increased incidence of FN has not been examined. Methods: A retrospective cohort design and US commercial claims data were used. The impact of CSF decision support was analyzed among women with breast cancer receiving first-cycle chemotherapy from April 1, 2013, to March 30, 2015. The tool was implemented as part of a prior authorization process in 9 states starting July 1, 2014. Patients were assigned to intervention (ie, states where the decision support tool had been implemented) or nonintervention states (ie, 39 states where the tool had not been implemented). CSF use and subsequent incidence of FN were compared using difference-in-difference (DID) regressions adjusting for baseline differences in FN risk factors such as comorbidities and various infections. Results: The study sample of 7,224 patients (intervention states: pre-implementation, 1,991 and post-implementation, 2,010; nonintervention states: pre-implementation, 1,569 and post-implementation, 1,654) showed no significant difference in risk factors. Before and after implementation, a significant decrease in the proportion of patients with CSF use was observed in the intervention states (75% to 69%) compared with no significant change in the nonintervention (72% to 71%) states (DID, –5.4%; 95% CI, –6.0% to –4.7%; P=.006). No significance increase in FN incidence occurred in intervention (5.0% to 5.5%) and nonintervention (5.4% to 4.8%) states (DID, 0.2%; 95% CI, –0.20 to 0.30; P=.78). Similar results were obtained in subgroups by comorbidities and in sensitivity analyses by claims-based FN definitions. Conclusions: CSF use decreased modestly after implementation of the decision support tool, with no observed changes in FN rates. Such tools can reduce practice variation to improve care standards.

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NCCN Guidelines Insights: T-Cell Lymphomas, Version 2.2018

Natural killer (NK)/T-cell lymphomas are a rare and distinct subtype of non-Hodgkin's lymphomas. NK/T-cell lymphomas are predominantly extranodal and most of these are nasal type, often localized to the upper aerodigestive tract. Because extranodal NK/T-cell lymphomas (ENKL) are rare malignancies, randomized trials comparing different regimens have not been conducted to date and standard therapy has not yet been established for these patients. These NCCN Guidelines Insights discuss the recommendations for the diagnosis and management of patients with ENKL as outlined in the NCCN Guidelines for T-Cell Lymphomas.

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Evolving Roles of Histologic Evaluation and Molecular/Genomic Profiling in the Management of Endometrial Cancer

Endometrial cancers are the most common gynecologic malignancies. The staging of endometrial cancer has evolved from a clinical-based system to a comprehensive surgical-pathologic approach that allows for better risk stratification and treatment planning. Over the past few years, use of NCCN's sentinel lymph node (SLN) mapping algorithm for the surgical staging of endometrial cancer has gained significant acceptance and is now commonly applied in many practices. However, pathologic evaluation of prognostic factors is beset by challenges, including the reproducibility of histologic classification and FIGO's grading, as well as the questionable clinical significance of low-volume tumor in SLNs. With the revelation of major genomic classes of endometrial cancer comes the potential for improved, reproducible, and prognostically relevant classification schemes, which integrate traditional pathologic parameters with genomic findings, to aid in treatment decisions. Pathologic identification of new variants of endometrial cancer, such as undifferentiated carcinoma, continues to advance the phenotypic spectrum of these tumors, spurring genomic and functional studies to further characterize their mechanistic underpinnings and potentially reveal new avenues for treatment. In the era of precision medicine, pathologic assessment of biomarkers (eg, mismatch repair proteins) and recognition of phenotypes that are amenable to specific targeted therapies (such as POLE-mutated tumors) have become integral to the management of women with endometrial carcinoma.

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Description of Venous Thromboembolism in Hospitalized Patients With Metastatic Cancer: A National Sample

Background: This study aimed to determine patient-, tumor-, and hospital-level characteristics associated with venous thromboembolism (VTE), and to assess the impact of VTE on in-hospital mortality and length of hospital stay in hospitalized patients with metastatic cancer. Methods: Using the Nationwide Inpatient Sample database, a cross-sectional analysis was performed of patients aged ≥18 years with at least 1 diagnosis of primary solid tumor and subsequent secondary or metastatic tumor between 2008 and 2013. Results: Among 850,570 patients with metastatic cancer, 6.6% were diagnosed with VTE. A significant trend for increasing VTE rates were observed from 2008 to 2013 (5.7%–7.2%; P<.0001). Using an adjusted multilevel hierarchical regression model, higher odds of VTE were seen among women (odds ratio [OR], 1.04; 95% CI, 1.02–1.06), black versus white patients (OR, 1.14; 95% CI, 1.11–1.18), and those with an Elixhauser comorbidity index score of ≥3 (OR, 2.50; 95% CI, 2.38–2.63). Hospital-level correlates of VTE included treatment in a teaching hospital (OR, 1.05; 95% CI, 1.01–1.11) and an urban location (OR, 1.18; 95% CI, 1.09–1.27), and admission to hospitals in the Northeast (OR, 1.16; 95% CI, 1.08–1.24) and West (OR, 1.09; 95% CI, 1.03–1.16) versus the South. Patients with metastasis to the liver, brain, or respiratory organs and those with multiple (≥2) metastatic sites had higher odds of VTE, whereas those with metastasis to lymph nodes and genital organs had lower odds. Patients diagnosed with versus without VTE had higher odds of in-hospital mortality (OR, 1.50; 95% CI, 1.38–1.63) and prolonged hospital stay (OR, 1.65; 95% CI, 1.57–1.73). Conclusions: The frequency of VTE in patients with metastatic cancer is increasing. Patient characteristics, hospital factors, and site of metastasis independently predict the occurrence of VTE and allow for better stratification of patients with cancer according to their VTE risk.

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In Memoriam: Jimmie C. Holland, MD (1928-2017)

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Macitentan senkt Lungengefäßwiderstand bei CTEPH

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 84-85
DOI: 10.1055/s-0044-101345

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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ARDS – Ein Update – Teil 1: Epidemiologie, Pathophysiologie und Diagnostik

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 102-111
DOI: 10.1055/s-0043-107166

Das akute Lungenversagen (Acute respiratory Distress Syndrome, ARDS) ist inzwischen seit mehr als 50 Jahren als schwerwiegende Komplikation unterschiedlicher Grunderkrankungen gefürchtet [1]. Häufig leiden ARDS-Patienten langfristig unter schwerwiegenden Beeinträchtigungen – auch nach primär erfolgreicher Therapie. Der erste Teil dieses Updates gibt einen aktualisierten Überblick zu Definition, Epidemiologie und Pathophysiologie des ARDS.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Fehlerhafte Daten in randomisierten Studien: Statistik kann sie aufdecken

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 82-82
DOI: 10.1055/s-0043-123125

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Schlafmangel – Einfluss auf Kommunikation und Interaktion im Team?

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 81-82
DOI: 10.1055/s-0044-101343

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Senkt die zusätzliche kontinuierliche Infusion von Tranexamsäure Blutverluste?

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 82-83
DOI: 10.1055/s-0044-101342

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Respiratorisches Versagen: Innovationen zur Diagnostik und Therapie

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 126-140
DOI: 10.1055/s-0043-108216

Die akute oder chronische respiratorische Insuffizienz hat eine große Bedeutung sowohl in der präklinischen als auch innerklinischen Versorgung. Sie zählt zu den häufigsten Gründen für stationäre Aufnahmen. Dieser Beitrag fasst aktuelle Entwicklungen in der Diagnostik und Therapie des Krankheitsbildes zusammen. Darüber hinaus gibt er einen Ausblick, wie sich die Behandlung in den kommenden Jahren weiterentwickeln könnte.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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Respiratorisches Versagen: State of the Art – Diagnose und Therapie

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 90-101
DOI: 10.1055/s-0043-107167

Die respiratorische Insuffizienz beschreibt die Unfähigkeit des Körpers, einen adäquaten Gasaustausch aufrechtzuerhalten. Sie stellt – insbesondere, wenn sie akut auftritt – einen lebensbedrohlichen Zustand dar, der umgehend therapiert werden muss. Dieser Artikel zeigt, welche Diagnostik erforderlich ist, um den Patienten schnell und korrekt behandeln zu können, und welche Therapieverfahren zur Verfügung stehen.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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Langzeitüberleben nach venovenöser ECMO

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 85-85
DOI: 10.1055/s-0044-101344

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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ARDS – Ein Update – Teil 2: Therapie und Outcome

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 112-125
DOI: 10.1055/s-0043-122136

Das Acute respiratory Distress Syndrome (ARDS) ist nunmehr seit über 50 Jahren als gravierende Komplikation verschiedener Grunderkrankungen bekannt [1]. Trotz intensiver Forschung in all dieser Zeit gibt es hinsichtlich der bestmöglichen Therapie des ARDS auch heute noch viele offene Fragen – insbesondere zur maschinellen Beatmung. Der zweite Teil des Update ARDS gibt einen aktualisierten Überblick zu Therapie und Outcome des ARDS.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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50 Jahre ARD-Forschung und -Therapie: Resümee und Ausblick

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 87-89
DOI: 10.1055/s-0043-124225

Georg Thieme Verlag KG Stuttgart · New York

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Behandlung der Sepsis und des septischen Schocks – die neuen Leitlinien

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 142-148
DOI: 10.1055/s-0043-114639

Die neue Leitlinie der Surviving Sepsis Campaign wurde im Jahr 2016 überarbeitet und im Jahr 2017 veröffentlicht. Darüber hinaus änderte sich durch „Sepsis-3" die Definition der Sepsis im Jahr 2016 grundlegend, von einer Inflammation mit Infektion hin zu einer „lebensbedrohlichen Organ-Dysfunktion, die durch eine fehlregulierte Wirtsreaktion" verursacht wird. Um die große Herausforderung zu bewältigen, die neuen Erkenntnisse zur Sepsisbehandlung mit der neuen Definition zu vereinen, wurden die Leitlinien vollständig neu strukturiert und umfassend überarbeitet. Die Leitlinie diskutiert die sepsisspezifische Behandlung und gibt Empfehlungen für allgemeine intensivmedizinische Maßnahmen. Der Artikel fasst die wichtigsten Empfehlungen zusammen und diskutiert zusätzlich einige entscheidende Änderungen. Dies soll den Leser ermutigen, die neue Leitlinie in den klinischen Alltag zu übernehmen und somit die Prognose der Patienten, die an einer Sepsis oder einem septischem Schock leiden, zu verbessern.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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Nierenersatzverfahren bei akuter Nierenschädigung – Indikation und Durchführung

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 150-157
DOI: 10.1055/s-0043-110038

Die akute Nierenschädigung ist eine häufige Komplikation kritisch kranker Patienten auf Intensivstationen, die mit einer hohen Morbidität und Letalität einhergeht [1]. Sie ist ein unabhängiger Risikofaktor für ein verschlechtertes Outcome kritisch kranker Patienten [2]. Diese Übersichtsarbeit fasst die verfügbare Evidenz für die Indikation und den Einsatz von Nierenersatzverfahren bei akuter Nierenschädigung anhand aktueller Literatur zusammen.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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Oncolytic Virus Therapy: Using Tumor-Targeting Viruses to Treat Cancer

A small but growing number of patients with cancer are being treated with oncolytic viruses, which infect and kill tumor cells. But research now suggests that these treatments also work against cancer by spurring an immune response.

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Oncolytic Virus Therapy: Using Tumor-Targeting Viruses to Treat Cancer

A small but growing number of patients with cancer are being treated with oncolytic viruses, which infect and kill tumor cells. But research now suggests that these treatments also work against cancer by spurring an immune response.

http://ift.tt/2sjSgQK

Independent validation of a new reirradiation risk score (RRRS) for glioma patients predicting post-recurrence survival: A multicenter DKTK/ROG analysis

Reirradiation (reRT) is a valid option with considerable efficacy in patients with recurrent high-grade glioma, but it is still not known which patients might be optimal candidates for a second course of irradiation. This study validated a newly developed prognostic score independently in an external patient cohort.

http://ift.tt/2ERFlbq

RHBDD1 promotes colorectal cancer metastasis through the Wnt signaling pathway and its downstream target ZEB1

40–50% of colorectal cancer (CRC) patients develop metastatic disease; the presence of metastasis hinders the effective treatment of cancer through surgery, chemotherapy and radiotherapy, which makes 5-year su...

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14, 15-EET induces breast cancer cell EMT and cisplatin resistance by up-regulating integrin αvβ3 and activating FAK/PI3K/AKT signaling

14,15-epoxyeicosatrienoic acid (14,15-EET) is an important lipid signaling molecule involved in the regulation of tumor metastasis, however, the role and molecular mechanisms of 14,15-EET activity in breast ca...

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Optimizing the prescription isodose level in stereotactic volumetric-modulated arc radiotherapy of lung lesions as a potential for dose de-escalation

To derive and exploit the optimal prescription isodose level (PIL) in inverse optimization of volumetric modulated arc radiotherapy (VMAT) as a potential approach to dose de–escalation in stereotactic body rad...

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Role of postoperative radiotherapy in reducing ipsilateral recurrence in DCIS: an observational study of 1048 cases

The objective of the present study was to evaluate the effectiveness of postoperative radiotherapy after breast conserving surgery (BCS) in DCIS in a large patient population treated in clinical practice.

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Dosimetric comparison between proton beam therapy and photon radiation therapy for locally advanced esophageal squamous cell carcinoma

The purpose of this study was to perform a dosimetric comparison between proton beam therapy (PBT) and photon radiation therapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who w...

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Optimizing the prescription isodose level in stereotactic volumetric-modulated arc radiotherapy of lung lesions as a potential for dose de-escalation

To derive and exploit the optimal prescription isodose level (PIL) in inverse optimization of volumetric modulated arc radiotherapy (VMAT) as a potential approach to dose de–escalation in stereotactic body rad...

http://ift.tt/2nZoOKK

Role of postoperative radiotherapy in reducing ipsilateral recurrence in DCIS: an observational study of 1048 cases

The objective of the present study was to evaluate the effectiveness of postoperative radiotherapy after breast conserving surgery (BCS) in DCIS in a large patient population treated in clinical practice.

http://ift.tt/2nLZqZC

Dosimetric comparison between proton beam therapy and photon radiation therapy for locally advanced esophageal squamous cell carcinoma

The purpose of this study was to perform a dosimetric comparison between proton beam therapy (PBT) and photon radiation therapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who w...

http://ift.tt/2nVHmvi

Can anticancer chemotherapy promote the progression of brain metastases?

Abstract

Brain metastases natural history from one primary tumor type might be accelerated or favored by using certain systemic chemotherapy. A great deal was described in mice and suggested in human with antiangiogenic drugs, but little is known about the metastatic progression generated by the perverse effect of anticancer drugs. A total of 413 patients who underwent treatment for brain metastasis (2013–2016) were included. The identification of all previous anticancer drugs received by patients from primary tumor diagnosis to brain metastases diagnosis was collated. The median value for the time of first appearance of brain metastasis in all patients was 13.1 months (SD 1.77). The values of brain metastasis-free survival (bMFS) for each primary cancer were: 50.9 months (SD 8.8) for breast, 28.5 months (SD 11.4) for digestive, 27.7 months (SD 18.3) for melanoma, 12.3 months (SD 8.3) for kidney, 1.5 months (SD 0.1) for lung and 26.9 months (SD 18.3) for others (p < 0.009). Through Cox multivariate proportional hazard model, we identified that the only independent factors associated with short bMFS were: lung primary tumor [odd ratio (OR) 0.234, CI 95% 0.16–0.42; p < 0.0001] and mitotic spindle inhibitor (taxanes) chemotherapy [OR 0.609, CI 95% 0.50–0.93; p < 0.001]. Contrariwise, breast primary tumor [odd ratio (OR) 2.372, CI 95% 1.29–4.3; p < 0.005] was an independent factor that proved a significantly longer bMFS. We suggest that anticancer drugs, especially taxane and its derivatives, could promote brain metastases, decreasing free survival. Mechanisms are discussed but still need to be determined.

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Efficacy comparison of transcervical video-assisted mediastinoscopic lymphadenectomy combined with left transthoracic esophagectomy versus right transthoracic esophagectomy for esophageal cancer treatment

Abstract

Background

This study aimed to propose a new surgical strategy, i.e., the transcervical video-assisted mediastinoscopic lymphadenectomy (VAMLA) with esophagectomy via the left transthoracic approach for patients with esophageal cancer (EC), and to compare the outcomes with those of esophagectomy via the right thoracic approach.

Methods

From December 2014 to March 2016, 49 cases were enrolled in this non-randomized concurrent control study. Twenty-eight patients with EC who underwent transcervical VAMLA with esophagectomy via the left transthoracic approach were assigned into the study group, while 21 EC patients undergoing esophagectomy via the right transthoracic approach during the same period were enrolled into the control group. Operative outcomes including operative time, the numbers of removed lymph nodes, intraoperative blood loss, the length of hospital stay, and postoperative complications in both groups were evaluated and compared.

Results

There were no significant differences in the baseline profiles between the two groups, and all patients in the two groups successfully underwent the surgery. There was a significant difference between transcervical VAMLA with esophagectomy via the left thoracic approach and esophagectomy via the right thoracic approach with regard to the number of all dissected lymph nodes [(29.0 ± 8.7) vs. (17.8 ± 8.1), p < 0.05], dissected superior mediastinal lymph nodes [(11.2 ± 5.0) vs. (3.7 ± 2.9), p < 0.05], and dissected in the recurrent laryngeal nerve lymph nodes [(5.6 ± 3.5) vs. (2.3 ± 2.1), p < 0.05]. No significant differences were observed in the operative time, intraoperative blood loss, length of postoperative hospital stay, number of dissected abdominal lymph nodes, postoperative pulmonary complications (pneumonia and atelectasis), anastomotic fistula, chylothorax, and vocal cord paralysis (p > 0.05).

Conclusion

Transcervical VAMLA combined with esophagectomy via the left thoracic approach appears technically feasible and safe and shows advantages in the number of dissected superior mediastinal lymph nodes, suggesting that it may serve as a new treatment option for patients with esophageal carcinoma.

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Can anticancer chemotherapy promote the progression of brain metastases?

Abstract

Brain metastases natural history from one primary tumor type might be accelerated or favored by using certain systemic chemotherapy. A great deal was described in mice and suggested in human with antiangiogenic drugs, but little is known about the metastatic progression generated by the perverse effect of anticancer drugs. A total of 413 patients who underwent treatment for brain metastasis (2013–2016) were included. The identification of all previous anticancer drugs received by patients from primary tumor diagnosis to brain metastases diagnosis was collated. The median value for the time of first appearance of brain metastasis in all patients was 13.1 months (SD 1.77). The values of brain metastasis-free survival (bMFS) for each primary cancer were: 50.9 months (SD 8.8) for breast, 28.5 months (SD 11.4) for digestive, 27.7 months (SD 18.3) for melanoma, 12.3 months (SD 8.3) for kidney, 1.5 months (SD 0.1) for lung and 26.9 months (SD 18.3) for others (p < 0.009). Through Cox multivariate proportional hazard model, we identified that the only independent factors associated with short bMFS were: lung primary tumor [odd ratio (OR) 0.234, CI 95% 0.16–0.42; p < 0.0001] and mitotic spindle inhibitor (taxanes) chemotherapy [OR 0.609, CI 95% 0.50–0.93; p < 0.001]. Contrariwise, breast primary tumor [odd ratio (OR) 2.372, CI 95% 1.29–4.3; p < 0.005] was an independent factor that proved a significantly longer bMFS. We suggest that anticancer drugs, especially taxane and its derivatives, could promote brain metastases, decreasing free survival. Mechanisms are discussed but still need to be determined.

http://ift.tt/2EgrXAA

Efficacy comparison of transcervical video-assisted mediastinoscopic lymphadenectomy combined with left transthoracic esophagectomy versus right transthoracic esophagectomy for esophageal cancer treatment

Abstract

Background

This study aimed to propose a new surgical strategy, i.e., the transcervical video-assisted mediastinoscopic lymphadenectomy (VAMLA) with esophagectomy via the left transthoracic approach for patients with esophageal cancer (EC), and to compare the outcomes with those of esophagectomy via the right thoracic approach.

Methods

From December 2014 to March 2016, 49 cases were enrolled in this non-randomized concurrent control study. Twenty-eight patients with EC who underwent transcervical VAMLA with esophagectomy via the left transthoracic approach were assigned into the study group, while 21 EC patients undergoing esophagectomy via the right transthoracic approach during the same period were enrolled into the control group. Operative outcomes including operative time, the numbers of removed lymph nodes, intraoperative blood loss, the length of hospital stay, and postoperative complications in both groups were evaluated and compared.

Results

There were no significant differences in the baseline profiles between the two groups, and all patients in the two groups successfully underwent the surgery. There was a significant difference between transcervical VAMLA with esophagectomy via the left thoracic approach and esophagectomy via the right thoracic approach with regard to the number of all dissected lymph nodes [(29.0 ± 8.7) vs. (17.8 ± 8.1), p < 0.05], dissected superior mediastinal lymph nodes [(11.2 ± 5.0) vs. (3.7 ± 2.9), p < 0.05], and dissected in the recurrent laryngeal nerve lymph nodes [(5.6 ± 3.5) vs. (2.3 ± 2.1), p < 0.05]. No significant differences were observed in the operative time, intraoperative blood loss, length of postoperative hospital stay, number of dissected abdominal lymph nodes, postoperative pulmonary complications (pneumonia and atelectasis), anastomotic fistula, chylothorax, and vocal cord paralysis (p > 0.05).

Conclusion

Transcervical VAMLA combined with esophagectomy via the left thoracic approach appears technically feasible and safe and shows advantages in the number of dissected superior mediastinal lymph nodes, suggesting that it may serve as a new treatment option for patients with esophageal carcinoma.

http://ift.tt/2sqRPo7

Solitary-fibrous tumor/hemangiopericytoma of the central nervous system: a population-based study

Abstract

The World Health Organization (WHO) classification of tumors of the central nervous system (CNS) was recently updated, restructuring solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) into one combined entity. This is the first population-based study to examine outcomes of SFT/HPC based on the new WHO guidelines. The Surveillance, Epidemiology, and End Results (SEER) database (1998–2013) was queried to examine age-adjusted incidence and prognostic factors associated with overall survival in 416 surgically resected cases. Age-adjusted incidence was calculated to be 3.77 per 10,000,000 and was rising. Median survival was 155 months, with 5- and 10-year survival rates of 78 and 61%, respectively. Younger age, Asian/Pacific Islander versus white race, benign histology, tumor location, gross-total resection (GTR), and GTR plus radiation (RT) versus subtotal resection were significantly associated with survival. In multivariable analysis, older age (HR = 1.038, p < 0.0001), infratentorial location (HR = 2.019, p = 0.038), GTR (HR = 0.313, p = 0.041), and GTR + RT (HR = 0.215, p = 0.008) were independent prognostic factors. In the HPC and borderline/malignant subgroups, GTR + RT was associated with significantly increased survival compared with GTR alone (HR = 0.537, p = 0.039 and HR = 0.525, p = 0.038). After eliminating patients that died within 3 months of diagnosis, GTR + RT was still associated with an incremental increase in survival (HR = 0.238, p = 0.031) over GTR alone (HR = 0.280, p = 0.054). GTR + RT may be optimal in the management CNS HPC and SFT/HPC tumors with borderline/malignant features. This study, in combination with existing literature, warrants further investigation of adjuvant radiation through a prospective clinical trial.

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Medulloblastoma with transitional features between Group 3 and Group 4 is associated with good prognosis

Abstract

Medulloblastoma, the most common malignant pediatric brain tumor, is a heterogeneous disease, with the existence of at least four molecular types: Wingless (WNT), Sonic Hedgehog (SHH), Group 3 and Group 4 tumors. The latter two groups, which can be identified by an application of multi-gene expression or methylation profiling, show sometimes ambiguous categorization and are still classified for diagnostic reason as non-SHH/non-WNT medulloblastomas in updated WHO 2016 classification. In order to better characterize non-SHH/non-WNT tumors, we applied the method based on the Nanostring nCounter Technology, using the 26 genes codeset in 68 uniformly treated medulloblastoma patients. This allowed for identification of tumors, which shared common Group 3 and Group 4 gene signatures. We recognized three transcriptional groups within non-WNT/non-SHH tumors: Group 3, Group 4 and the Intermediate 3/4 Group. Group 3, in line with previously published results, showed poor prognosis with survival rate < 40%, frequent metastases, large cell/anaplastic pathology and presence of tumors with MYCC amplification. This is in contrast to patients from the Intermediate 3/4 Group who showed the best survival rate (100%). Overall and progression free survival were better for this group than for Group 3 (p = 0.001, for both) and Group 4 (p = 0.064 and p = 0.066, respectively). Our work supports the view that within the non-WNT/non-SHH tumors different risk groups exist and that the current two groups classifier may be not sufficient for proper clinical categorization of individual patients.

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Solitary-fibrous tumor/hemangiopericytoma of the central nervous system: a population-based study

Abstract

The World Health Organization (WHO) classification of tumors of the central nervous system (CNS) was recently updated, restructuring solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) into one combined entity. This is the first population-based study to examine outcomes of SFT/HPC based on the new WHO guidelines. The Surveillance, Epidemiology, and End Results (SEER) database (1998–2013) was queried to examine age-adjusted incidence and prognostic factors associated with overall survival in 416 surgically resected cases. Age-adjusted incidence was calculated to be 3.77 per 10,000,000 and was rising. Median survival was 155 months, with 5- and 10-year survival rates of 78 and 61%, respectively. Younger age, Asian/Pacific Islander versus white race, benign histology, tumor location, gross-total resection (GTR), and GTR plus radiation (RT) versus subtotal resection were significantly associated with survival. In multivariable analysis, older age (HR = 1.038, p < 0.0001), infratentorial location (HR = 2.019, p = 0.038), GTR (HR = 0.313, p = 0.041), and GTR + RT (HR = 0.215, p = 0.008) were independent prognostic factors. In the HPC and borderline/malignant subgroups, GTR + RT was associated with significantly increased survival compared with GTR alone (HR = 0.537, p = 0.039 and HR = 0.525, p = 0.038). After eliminating patients that died within 3 months of diagnosis, GTR + RT was still associated with an incremental increase in survival (HR = 0.238, p = 0.031) over GTR alone (HR = 0.280, p = 0.054). GTR + RT may be optimal in the management CNS HPC and SFT/HPC tumors with borderline/malignant features. This study, in combination with existing literature, warrants further investigation of adjuvant radiation through a prospective clinical trial.

http://ift.tt/2Efq07B

Medulloblastoma with transitional features between Group 3 and Group 4 is associated with good prognosis

Abstract

Medulloblastoma, the most common malignant pediatric brain tumor, is a heterogeneous disease, with the existence of at least four molecular types: Wingless (WNT), Sonic Hedgehog (SHH), Group 3 and Group 4 tumors. The latter two groups, which can be identified by an application of multi-gene expression or methylation profiling, show sometimes ambiguous categorization and are still classified for diagnostic reason as non-SHH/non-WNT medulloblastomas in updated WHO 2016 classification. In order to better characterize non-SHH/non-WNT tumors, we applied the method based on the Nanostring nCounter Technology, using the 26 genes codeset in 68 uniformly treated medulloblastoma patients. This allowed for identification of tumors, which shared common Group 3 and Group 4 gene signatures. We recognized three transcriptional groups within non-WNT/non-SHH tumors: Group 3, Group 4 and the Intermediate 3/4 Group. Group 3, in line with previously published results, showed poor prognosis with survival rate < 40%, frequent metastases, large cell/anaplastic pathology and presence of tumors with MYCC amplification. This is in contrast to patients from the Intermediate 3/4 Group who showed the best survival rate (100%). Overall and progression free survival were better for this group than for Group 3 (p = 0.001, for both) and Group 4 (p = 0.064 and p = 0.066, respectively). Our work supports the view that within the non-WNT/non-SHH tumors different risk groups exist and that the current two groups classifier may be not sufficient for proper clinical categorization of individual patients.

http://ift.tt/2CbGKXC

Cancers, Vol. 10, Pages 46: Liver Transplantation for Alcoholic Liver Disease and Hepatocellular Carcinoma

Cancers, Vol. 10, Pages 46: Liver Transplantation for Alcoholic Liver Disease and Hepatocellular Carcinoma

Cancers doi: 10.3390/cancers10020046

Authors: Patrizia Burra Alberto Zanetto Giacomo Germani

Hepatocellular carcinoma is one of the main important causes of cancer-related death and its mortality is increasingly worldwide. In Europe, alcohol abuse accounts for approximately half of all liver cancer cases and it will become the leading cause of hepatocellular carcinoma in the next future with the sharp decline of chronic viral hepatitis. The pathophysiology of alcohol-induced carcinogenesis involves acetaldehyde catabolism, oxidative stress and chronic liver inflammation. Genetic background plays also a significant role and specific patterns of gene mutations in alcohol-related hepatocellular carcinoma have been characterized. Survival is higher in patients who undergo specific surveillance programmes than in patients who do not. However, patients with alcohol cirrhosis present a significantly greater risk of liver decompensation than those with cirrhosis due to other aetiologies. Furthermore, the adherence to screening program can be suboptimal. Liver transplant for patients with Milan-in hepatocellular carcinoma represents the best possible treatment in case of tumour recurrence/progression despite loco-regional or surgical treatments. Long-term result after liver transplantation for alcohol related liver disease is good. However, cardiovascular disease and de novo malignancies can significantly hamper patients' survival and should be carefully considered by transplant team. In this review, we have focused on the evolution of alcohol-related hepatocellular carcinoma epidemiology and risk factors as well as on liver transplantation in alcoholic patients with and without hepatocellular carcinoma.

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Cancers, Vol. 10, Pages 47: Bioapplications of Cell-SELEX-Generated Aptamers in Cancer Diagnostics, Therapeutics, Theranostics and Biomarker Discovery: A Comprehensive Review

Cancers, Vol. 10, Pages 47: Bioapplications of Cell-SELEX-Generated Aptamers in Cancer Diagnostics, Therapeutics, Theranostics and Biomarker Discovery: A Comprehensive Review

Cancers doi: 10.3390/cancers10020047

Authors: Xuehui Pang Cheng Cui Shuo Wan Ying Jiang Liangliang Zhang Lian Xia Long Li Xiaowei Li Weihong Tan

Currently, functional single-stranded oligonucleotide probes, termed aptamers, generated by an iterative technology, Systematic Evolution of Ligands by Exponential Enrichment (SELEX), are utilized to selectively target molecules or cells with high affinity. Aptamers hold considerable promise as multifunctional molecules or conjugates for challenging nanotechnologies or bioapplications now and in the future. In this review, we first describe recent endeavors to select aptamers towards live cancer cells via cell-SELEX. We then introduce several characteristic applications of selected aptamers, especially in imaging, drug delivery and therapy. In part, these advances have been made possible via synthesis of aptamer-based nanomaterials, which, by their sizes, shapes, and physicochemical properties, allow such aptamer-nanomaterial complexes to function as signal reporters or drug carriers. We also describe how these aptamer-based molecular tools contribute to cancer biomarker discovery through high-affinity recognition of membrane protein receptors.

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Cancers, Vol. 10, Pages 46: Liver Transplantation for Alcoholic Liver Disease and Hepatocellular Carcinoma

Cancers, Vol. 10, Pages 46: Liver Transplantation for Alcoholic Liver Disease and Hepatocellular Carcinoma

Cancers doi: 10.3390/cancers10020046

Authors: Patrizia Burra Alberto Zanetto Giacomo Germani

Hepatocellular carcinoma is one of the main important causes of cancer-related death and its mortality is increasingly worldwide. In Europe, alcohol abuse accounts for approximately half of all liver cancer cases and it will become the leading cause of hepatocellular carcinoma in the next future with the sharp decline of chronic viral hepatitis. The pathophysiology of alcohol-induced carcinogenesis involves acetaldehyde catabolism, oxidative stress and chronic liver inflammation. Genetic background plays also a significant role and specific patterns of gene mutations in alcohol-related hepatocellular carcinoma have been characterized. Survival is higher in patients who undergo specific surveillance programmes than in patients who do not. However, patients with alcohol cirrhosis present a significantly greater risk of liver decompensation than those with cirrhosis due to other aetiologies. Furthermore, the adherence to screening program can be suboptimal. Liver transplant for patients with Milan-in hepatocellular carcinoma represents the best possible treatment in case of tumour recurrence/progression despite loco-regional or surgical treatments. Long-term result after liver transplantation for alcohol related liver disease is good. However, cardiovascular disease and de novo malignancies can significantly hamper patients' survival and should be carefully considered by transplant team. In this review, we have focused on the evolution of alcohol-related hepatocellular carcinoma epidemiology and risk factors as well as on liver transplantation in alcoholic patients with and without hepatocellular carcinoma.

http://ift.tt/2ESzQsV

Cancers, Vol. 10, Pages 47: Bioapplications of Cell-SELEX-Generated Aptamers in Cancer Diagnostics, Therapeutics, Theranostics and Biomarker Discovery: A Comprehensive Review

Cancers, Vol. 10, Pages 47: Bioapplications of Cell-SELEX-Generated Aptamers in Cancer Diagnostics, Therapeutics, Theranostics and Biomarker Discovery: A Comprehensive Review

Cancers doi: 10.3390/cancers10020047

Authors: Xuehui Pang Cheng Cui Shuo Wan Ying Jiang Liangliang Zhang Lian Xia Long Li Xiaowei Li Weihong Tan

Currently, functional single-stranded oligonucleotide probes, termed aptamers, generated by an iterative technology, Systematic Evolution of Ligands by Exponential Enrichment (SELEX), are utilized to selectively target molecules or cells with high affinity. Aptamers hold considerable promise as multifunctional molecules or conjugates for challenging nanotechnologies or bioapplications now and in the future. In this review, we first describe recent endeavors to select aptamers towards live cancer cells via cell-SELEX. We then introduce several characteristic applications of selected aptamers, especially in imaging, drug delivery and therapy. In part, these advances have been made possible via synthesis of aptamer-based nanomaterials, which, by their sizes, shapes, and physicochemical properties, allow such aptamer-nanomaterial complexes to function as signal reporters or drug carriers. We also describe how these aptamer-based molecular tools contribute to cancer biomarker discovery through high-affinity recognition of membrane protein receptors.

http://ift.tt/2nYHJF8

The impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features on the rate of malignancy for atypia of undetermined significance subcategories

BACKGROUND

The recent revision in terminology, with noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) replacing noninvasive follicular variant of papillary thyroid carcinoma, has reclassified the clinically indolent tumor as nonmalignant. The objective of this study was to evaluate the impact of this change on the rate of malignancy (ROM) for subcategories of an atypia of undetermined significance (AUS) diagnosis on fine-needle aspiration (FNA) cytology.

METHODS

Consecutive thyroid FNAs interpreted as AUS over a period of 4 years were retrospectively analyzed. The ROM for AUS subcategories, including atypia of undetermined significance with nuclear atypia (AUS-N), atypia of undetermined significance with a microfollicular pattern (AUS-F), atypia of undetermined significance with nuclear atypia and a microfollicular pattern (AUS-N/F), atypia of undetermined significance with Hürthle cells (AUS-H), and atypia of undetermined significance, not otherwise specified (AUS-NOS), were analyzed.

RESULTS

Of the 426 nodules interpreted as AUS, 244 were surgically excised. The incidence of NIFTP in each subcategory was as follows: 18% for AUS-N, 18% for AUS-F, 9% for AUS-N/F, 3% for AUS-H, and 0% for AUS-NOS. After the reclassification of NIFTP as nonmalignant, the ROM based on histologic follow-up significantly decreased from 43% to 26% for AUS-N (P < .001) and from 29% to 10% for AUS-F (P = .008). The ROM for AUS-N remained significantly higher than the ROM for AUS-F (P = .030).

CONCLUSIONS

A subset of resected AUS nodules can be reclassified as NIFTP, and that significantly decreases the ROM, especially for AUS-N and AUS-F. Nonetheless, AUS-N still harbors a substantially higher ROM than AUS-F. Cancer Cytopathol 2018. © 2018 American Cancer Society.

http://ift.tt/2BjVV3T

The impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features on the rate of malignancy for atypia of undetermined significance subcategories

BACKGROUND

The recent revision in terminology, with noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) replacing noninvasive follicular variant of papillary thyroid carcinoma, has reclassified the clinically indolent tumor as nonmalignant. The objective of this study was to evaluate the impact of this change on the rate of malignancy (ROM) for subcategories of an atypia of undetermined significance (AUS) diagnosis on fine-needle aspiration (FNA) cytology.

METHODS

Consecutive thyroid FNAs interpreted as AUS over a period of 4 years were retrospectively analyzed. The ROM for AUS subcategories, including atypia of undetermined significance with nuclear atypia (AUS-N), atypia of undetermined significance with a microfollicular pattern (AUS-F), atypia of undetermined significance with nuclear atypia and a microfollicular pattern (AUS-N/F), atypia of undetermined significance with Hürthle cells (AUS-H), and atypia of undetermined significance, not otherwise specified (AUS-NOS), were analyzed.

RESULTS

Of the 426 nodules interpreted as AUS, 244 were surgically excised. The incidence of NIFTP in each subcategory was as follows: 18% for AUS-N, 18% for AUS-F, 9% for AUS-N/F, 3% for AUS-H, and 0% for AUS-NOS. After the reclassification of NIFTP as nonmalignant, the ROM based on histologic follow-up significantly decreased from 43% to 26% for AUS-N (P < .001) and from 29% to 10% for AUS-F (P = .008). The ROM for AUS-N remained significantly higher than the ROM for AUS-F (P = .030).

CONCLUSIONS

A subset of resected AUS nodules can be reclassified as NIFTP, and that significantly decreases the ROM, especially for AUS-N and AUS-F. Nonetheless, AUS-N still harbors a substantially higher ROM than AUS-F. Cancer Cytopathol 2018. © 2018 American Cancer Society.

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Treatment with 5-azacitidine delay growth of glioblastoma xenografts: a potential new treatment approach for glioblastomas

Abstract

Purpose

Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults. The epigenetically active ribonucleoside analog 5-azacitidine is a new therapy option that changes tumor cell chromatin, which is frequently modified by methylation and deacetylation in malignant gliomas.

Methods

In vitro, we analyzed cell viability, cell apoptosis, and migration of human GBM cells. In vivo, we established subcutaneous and intracerebral GBM mouse models originating from U87MG, U373MG, and primary GBM cells as well as one patient-derived xenograft. Xenografts were treated with 5-azacitidine as well as valproic acid, bevacizumab, temozolomide, and phosphate buffered saline. The tumor sizes and Ki67 proliferation indices were determined. Glioma angiogenesis was examined immunohistochemically by expression analysis of endothelial cells (CD31) and pericytes (PDGFRβ).

Results

In vitro, 5-azacitidine treatment significantly reduced human glioblastoma cell viability, increased cellular apoptosis, and reduced cellular migration. In vivo, 5-azacitidine significantly reduced growth in two intracerebral GBM models. Notably, this was also shown for a xenograft established from a patient surgery sample; whereas, epigenetically acting valproic acid did not show any growth reduction. Highly vascularized tumors responded to treatment, whereas low-vascularized xenografts showed no response. Furthermore, intracerebral glioblastomas treated with 5-azacitidine showed a clearly visible reduction of tumor angiogenesis and lower numbers of endothelial cells and tumor vessel pericytes.

Conclusions

Our data show significant growth inhibition as well as antiangiogenic effects in intracerebral as well as patient-derived GBM xenografts. This encourages to investigate in detail the multifactorial effects of 5-azacitidine on glioblastomas.

http://ift.tt/2nWenaK

Treatment with 5-azacitidine delay growth of glioblastoma xenografts: a potential new treatment approach for glioblastomas

Abstract

Purpose

Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults. The epigenetically active ribonucleoside analog 5-azacitidine is a new therapy option that changes tumor cell chromatin, which is frequently modified by methylation and deacetylation in malignant gliomas.

Methods

In vitro, we analyzed cell viability, cell apoptosis, and migration of human GBM cells. In vivo, we established subcutaneous and intracerebral GBM mouse models originating from U87MG, U373MG, and primary GBM cells as well as one patient-derived xenograft. Xenografts were treated with 5-azacitidine as well as valproic acid, bevacizumab, temozolomide, and phosphate buffered saline. The tumor sizes and Ki67 proliferation indices were determined. Glioma angiogenesis was examined immunohistochemically by expression analysis of endothelial cells (CD31) and pericytes (PDGFRβ).

Results

In vitro, 5-azacitidine treatment significantly reduced human glioblastoma cell viability, increased cellular apoptosis, and reduced cellular migration. In vivo, 5-azacitidine significantly reduced growth in two intracerebral GBM models. Notably, this was also shown for a xenograft established from a patient surgery sample; whereas, epigenetically acting valproic acid did not show any growth reduction. Highly vascularized tumors responded to treatment, whereas low-vascularized xenografts showed no response. Furthermore, intracerebral glioblastomas treated with 5-azacitidine showed a clearly visible reduction of tumor angiogenesis and lower numbers of endothelial cells and tumor vessel pericytes.

Conclusions

Our data show significant growth inhibition as well as antiangiogenic effects in intracerebral as well as patient-derived GBM xenografts. This encourages to investigate in detail the multifactorial effects of 5-azacitidine on glioblastomas.

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Checkpoint inhibitors in triple-negative breast cancer (TNBC): Where to go from here

Advances in cancer immunotherapy and a growing body of research have focused on the role of the antitumor response in breast cancer. Triple-negative breast cancer (TNBC) is the most immunogenic breast cancer subtype, and there is strong evidence that tumor-infiltrating lymphocytes in TNBC have prognostic value and are associated with clinical outcome and improved survival. Evading antitumor immunity is a hallmark for the development and progression of cancer. Immunotherapy studies have focused on the role of the programmed cell death-1 (PD-1) receptor/programmed death-ligand 1 (PD-L1) pathway in maintaining immunosuppression in the tumor microenvironment. Blockade of the PD-1/PD-L1 axis has emerged as a promising therapeutic option to enhance antitumor immunity and is actively being investigated in TNBC, with encouraging results. In this article, the authors review the current literature on checkpoint inhibitors in TNBC with a focus on PD-1/PD-L1 antibodies and discuss combination strategies and novel approaches for improving antitumor immunity and clinical outcome. Cancer 2018. © 2018 American Cancer Society.

http://ift.tt/2Bk5Vdw

Allogeneic hematopoietic stem cell transplantation for relapsed follicular lymphoma: A combined analysis on behalf of the Lymphoma Working Party of the EBMT and the Lymphoma Committee of the CIBMTR

BACKGROUND

Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains the only potentially curative treatment option for relapsed follicular lymphoma (FL), yet questions remain about the optimal timing. This study analyzed long-term outcomes and associated factors among recipients of allo-HCT with FL.

METHODS

Patients with relapsed FL who underwent allo-HCT from 2001 to 2011 with a human leukocyte antigen (HLA)–matched donor were included. Outcome analyses for overall survival (OS), progression-free survival (PFS), transplant-related mortality (TRM), and disease relapse/progression were calculated. A multivariate analysis was performed to determine factors associated with outcomes, and a prognostic score for treatment failure was developed in a subset analysis of patients.

RESULTS

In all, 1567 patients with relapsed FL were included; the median follow-up was 55 months. The 5-year probabilities of OS and PFS were 61% and 52%, respectively. The 5-year cumulative incidences of disease progression/relapse and TRM were 29% and 19%, respectively. Chemoresistant disease, older age, heavy pretreatment, poor performance status (PS), and myeloablative protocols were predictors for worse survival. The prognostic score, using age, lines of prior therapy, disease status, and PS, stratified patients into 3 groups—low, intermediate, and high risk—with 5-year PFS rates of 68%, 53%, and 46%, respectively, and 5-year OS rates of 80%, 62%, and 50%, respectively.

CONCLUSIONS

Allo-HCT should be considered for patients with relapsed FL and available HLA-matched donors. Outcomes are better in earlier phases of the disease, and reduced-intensity conditioning should be preferred. The prognostic score presented here can assist in counseling patients and determining the time to proceed to transplantation. Cancer 2018. © 2018 American Cancer Society.

http://ift.tt/2BOe234

Checkpoint inhibitors in triple-negative breast cancer (TNBC): Where to go from here

Advances in cancer immunotherapy and a growing body of research have focused on the role of the antitumor response in breast cancer. Triple-negative breast cancer (TNBC) is the most immunogenic breast cancer subtype, and there is strong evidence that tumor-infiltrating lymphocytes in TNBC have prognostic value and are associated with clinical outcome and improved survival. Evading antitumor immunity is a hallmark for the development and progression of cancer. Immunotherapy studies have focused on the role of the programmed cell death-1 (PD-1) receptor/programmed death-ligand 1 (PD-L1) pathway in maintaining immunosuppression in the tumor microenvironment. Blockade of the PD-1/PD-L1 axis has emerged as a promising therapeutic option to enhance antitumor immunity and is actively being investigated in TNBC, with encouraging results. In this article, the authors review the current literature on checkpoint inhibitors in TNBC with a focus on PD-1/PD-L1 antibodies and discuss combination strategies and novel approaches for improving antitumor immunity and clinical outcome. Cancer 2018. © 2018 American Cancer Society.

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Allogeneic hematopoietic stem cell transplantation for relapsed follicular lymphoma: A combined analysis on behalf of the Lymphoma Working Party of the EBMT and the Lymphoma Committee of the CIBMTR

BACKGROUND

Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains the only potentially curative treatment option for relapsed follicular lymphoma (FL), yet questions remain about the optimal timing. This study analyzed long-term outcomes and associated factors among recipients of allo-HCT with FL.

METHODS

Patients with relapsed FL who underwent allo-HCT from 2001 to 2011 with a human leukocyte antigen (HLA)–matched donor were included. Outcome analyses for overall survival (OS), progression-free survival (PFS), transplant-related mortality (TRM), and disease relapse/progression were calculated. A multivariate analysis was performed to determine factors associated with outcomes, and a prognostic score for treatment failure was developed in a subset analysis of patients.

RESULTS

In all, 1567 patients with relapsed FL were included; the median follow-up was 55 months. The 5-year probabilities of OS and PFS were 61% and 52%, respectively. The 5-year cumulative incidences of disease progression/relapse and TRM were 29% and 19%, respectively. Chemoresistant disease, older age, heavy pretreatment, poor performance status (PS), and myeloablative protocols were predictors for worse survival. The prognostic score, using age, lines of prior therapy, disease status, and PS, stratified patients into 3 groups—low, intermediate, and high risk—with 5-year PFS rates of 68%, 53%, and 46%, respectively, and 5-year OS rates of 80%, 62%, and 50%, respectively.

CONCLUSIONS

Allo-HCT should be considered for patients with relapsed FL and available HLA-matched donors. Outcomes are better in earlier phases of the disease, and reduced-intensity conditioning should be preferred. The prognostic score presented here can assist in counseling patients and determining the time to proceed to transplantation. Cancer 2018. © 2018 American Cancer Society.

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Pleomorphic liposarcoma of bone: a rare primary malignant bone tumour

Abstract

Background

Liposarcoma is an extremely rare primary bone sarcoma.

Case presentation

We report a case of primary pleomorphic liposarcoma that arose in an 18 year old male in the metaphysis of the left tibia. Plain radiographs showed a partly sclerotic lesion and MR imaging a heterogeneous tumour predominantly isointense on T1- and high-signal on T2-weighted sequences with focal areas of increased T1 signal that suppressed with fat saturation. PET/CT showed marked FDG uptake (SUV = 17.1) in the primary tumour as well as a metastasis in the right distal femur and multiple small pulmonary metastases. Histologically, the tumour was a pleomorphic liposarcoma containing large tumour cells with vacuolated cytoplasm and hyperchromatic pleomorphic nuclei as well as numerous lipoblasts and scattered brown fat-like cells. Tumour cells strongly expressed FABP4/aP2, a marker of adipocyte differentiation, and UCP1, a marker of brown fat, but not S100. The case was treated with neoadjuvant MAP chemotherapy, resulting in extensive (> 95%) necrosis in the primary tumour and almost complete resolution of the femoral and pulmonary metastases.

Conclusions

Pleomorphic liposarcoma can present as a sclerotic primary malignant bone tumour; markers of adipose differentiation are useful in histological diagnosis and neoadjuvant MAP chemotherapy results in significant tumor necrosis.

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Pleomorphic liposarcoma of bone: a rare primary malignant bone tumour

Abstract

Background

Liposarcoma is an extremely rare primary bone sarcoma.

Case presentation

We report a case of primary pleomorphic liposarcoma that arose in an 18 year old male in the metaphysis of the left tibia. Plain radiographs showed a partly sclerotic lesion and MR imaging a heterogeneous tumour predominantly isointense on T1- and high-signal on T2-weighted sequences with focal areas of increased T1 signal that suppressed with fat saturation. PET/CT showed marked FDG uptake (SUV = 17.1) in the primary tumour as well as a metastasis in the right distal femur and multiple small pulmonary metastases. Histologically, the tumour was a pleomorphic liposarcoma containing large tumour cells with vacuolated cytoplasm and hyperchromatic pleomorphic nuclei as well as numerous lipoblasts and scattered brown fat-like cells. Tumour cells strongly expressed FABP4/aP2, a marker of adipocyte differentiation, and UCP1, a marker of brown fat, but not S100. The case was treated with neoadjuvant MAP chemotherapy, resulting in extensive (> 95%) necrosis in the primary tumour and almost complete resolution of the femoral and pulmonary metastases.

Conclusions

Pleomorphic liposarcoma can present as a sclerotic primary malignant bone tumour; markers of adipose differentiation are useful in histological diagnosis and neoadjuvant MAP chemotherapy results in significant tumor necrosis.

http://ift.tt/2sqsmv1