In recent reports, re-irradiation with stereotactic body radiotherapy for lung tumors in patients previously treated with thoracic radiation therapy resulted in several serious toxicities. Serious non-lung tox...
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Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Σάββατο 9 Δεκεμβρίου 2017
Serious gastric perforation after second stereotactic body radiotherapy for peripheral lung cancer that recurred after initial stereotactic body radiotherapy: a case report
Prior systemic treatment increased the incidence of somatic mutations in metastatic breast cancer
Source:European Journal of Cancer, Volume 89
Author(s): Takeo Fujii, Naoko Matsuda, Miho Kono, Kenichi Harano, Huiqin Chen, Rajyalakshmi Luthra, Sinchita Roy-Chowdhuri, Aysegul A. Sahin, Chetna Wathoo, Aron Y. Joon, Debu Tripathy, Funda Meric-Bernstam, Naoto T. Ueno
BackgroundUnderstanding the biology of breast cancer is important for guiding treatment strategies and revealing resistance mechanisms. Our objectives were to investigate the relationship between previous systemic therapy exposure and mutational spectrum in metastatic breast cancer and to identify clinicopathological factors associated with identified frequent somatic mutations.MethodsArchival tissues of patients with metastatic breast cancer were subjected to hotspot molecular testing by next-generation sequencing. The variables that significantly differed (P < 0.05) in univariate analysis were selected to fit multivariate models. Logistic models were fit to estimate the association between mutation status and clinical variables of interest. Five-fold cross-validation was performed to estimate the prediction error of each model.ResultsA total of 922 patients were included in the analysis. In multivariate analysis, previous systemic treatment before molecular testing (N = 186) was associated with a significantly higher rate of TP53 and PIK3CA mutations compared with the lack of systemic treatment (P < 0.001 for both).ConclusionSystemic treatment exposure is an independent risk factor for high rates of TP53 and PIK3CA mutation, which suggests the importance of testing samples after systemic therapy to accurately assess mutations. It is worth testing the gene profile when tumours become resistant to systemic treatments.
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Complete response of a metastatic porocarcinoma treated with paclitaxel, cetuximab and radiotherapy
Source:European Journal of Cancer
Author(s): C. Godillot, S. Boulinguez, L. Riffaud, V. Sibaud, C. Chira, E. Tournier, C. Paul, N. Meyer
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Geographic Variation of Adjuvant Breast Cancer Therapy Initiation in the United States: Lessons From Medicare Part D
Background: Drug utilization under Medicare Part D varies significantly by geographic region. This study examined the extent to which geographic variation in Part D plan characteristics contributes to the variation in choice of initial endocrine therapy agent among women with incident breast cancer. Methods: Two-stage multivariate regression analyses were applied to the 16,541 women identified from Medicare claims as having incident breast cancer in 2006–2007. The first stage determined the effect of state of residence on the probability of having an aromatase inhibitor (AI), as opposed to tamoxifen, as initial endocrine therapy. The second stage provided estimates of the impact of state-specific Part D plan characteristics on variation in choice of initial therapy. Results: There was substantial residual geographic variation in the likelihood of using an AI as initial endocrine therapy, despite controlling for socioeconomic status, breast cancer treatment, and other factors. Regression-adjusted probabilities of starting an AI ranged from 57.3% in Wyoming to 92.6% in the District of Columbia. Results from the second stage revealed that variation in characteristics of Part D plans across states explained approximately one-third (30%) of the state-level variability in endocrine therapy. A higher number of plans with cost-sharing above the mean, greater spread in deductibles, and a greater spread in monthly drug premiums were associated with lower adjusted state probabilities of initiating an AI. In contrast, a higher number of drug plans with monthly premiums above the state mean and higher mean cost-sharing (in dollars) were both positively associated with likelihood of starting on an AI. Conclusions: Study findings suggest that variation in benefit design of Part D plans accounts for an important share of the large and persisting variability in use of AIs—the preferred oral therapy for breast cancer.
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Myeloid Growth Factors, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology
Myeloid growth factors (MGFs) are given as supportive care to patients receiving myelosuppressive chemotherapy to reduce the incidence of neutropenia. This selection from the NCCN Guidelines for MGFs focuses on the evaluation of regimen- and patient-specific risk factors for the development of febrile neutropenia (FN), the prophylactic use of MGFs for the prevention of chemotherapy-induced FN, and assessing the risks and benefits of MGF use in clinical practice.
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KRAS Testing, Tumor Location, and Survival in Patients With Stage IV Colorectal Cancer: SEER 2010-2013
Purpose: KRAS mutations and tumor location have been associated with response to targeted therapy among patients with stage IV colorectal cancer (CRC) in various trials. This study performed the first population-based examination of associations between KRAS mutations, tumor location, and survival, and assessed factors associated with documented KRAS testing. Methods: Patients with stage IV adenocarcinoma of the colon/rectum diagnosed from 2010 to 2013 were extracted from SEER data. Analyses of patient characteristics, KRAS testing, and tumor location were conducted using logistic regression. Cox proportional hazards models assessed relationships between KRAS mutations, tumor location, and risk of all-cause death. Results: Of 22,542 patients, 30% received KRAS testing, and 44% of these had mutations. Those tested tended to be younger, married, and metropolitan area residents, and have private insurance or Medicare. Rates of KRAS testing also varied by registry (range, 20%–46%). Patients with right-sided colon cancer (vs left-sided) tended to be older, female, and black; have mucinous, KRAS-mutant tumors; and have a greater risk of death (hazard ratio [HR], 1.27; 95% CI, 1.22–1.32). KRAS mutations were not associated with greater risk of death in the overall population; however, they were associated with greater risk of death among patients with left-sided colon cancer (HR, 1.19; 95% CI, 1.05–1.33). Conclusions: This large population-based study showed that among patients initially diagnosed with stage IV CRC, right-sided colon cancer was associated with greater risk of death compared with left-sided cancer, and KRAS mutations were only associated with risk of death in left-sided colon cancer. An unexpected finding was that among patients with stage IV disease, right-sided cancer was more commonly seen in black patients versus whites. Future studies should further explore these associations and determine the role of biology versus treatment differences. In addition, use of KRAS testing is increasing, but there is wide geographic variation wherein disparities related to insurance coverage and rurality may warrant further study.
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Prevalence of Physical Problems Detected by the Distress Thermometer and Problem List in Patients With Myeloproliferative Disorders
Background: Patients with myeloproliferative neoplasms (MPNs) can have a severe physical symptom burden over an extended disease trajectory that contributes to decreased quality of life. Few studies, however, have characterized which patients most frequently consider physical symptoms a problem. This study describes the physical symptoms of patients with MPNs and the relationship of these symptoms to patient characteristics. Methods: Patients with MPNs (N=117) completed questionnaires in a dedicated academic medical center MPN clinic. Patients reported demographics (age, race/ethnicity, sex, marital status, employment status), disease characteristics (MPN type, time with MPN), and whether they were bothered by any of 22 variables in the "Physical Problems" list in the Distress Thermometer and Problem List (DT&PL). Results: The median number of physical problems endorsed by patients was 2 (median, 2.26; SD, 3.18), with a range from 0 to 20. Two-fifths endorsed no physical problems, one-fifth endorsed 1 problem, and two-fifths endorsed ≥2 problems, with fatigue (35.5%), sleep (27.1%), pain (21.5%), dry skin/pruritus (18.7%), and memory/concentration (16.8%) being the most commonly reported. Non-Caucasian participants reported more problems with sleep (P=.050), pain (P=.016), and tingling (P=.026). Patients with polycythemia vera (PV) reported more issues with tingling (P=.046) and sexual problems (P=.032). Conclusions: Patients with MPNs are more likely to report physical symptom bother than to report no bother with multiple physical problems on the DT&PL. Patients of minority race/ethnicity and those with PV, however, showed heightened prevalence of physical problems—characteristics which may be used to triage patients for more intensive symptom management.
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Controversies Regarding Use of Myeloid Growth Factors in Leukemia
This review focuses on the data supporting the use of myeloid growth factors (MGFs) in patients being treated for acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and hairy cell leukemia, for which neutropenia is a common complication of treatment. However, due to the lack of randomized trial data or conflicting results of clinical studies, comprehensive guidelines have been difficult to formulate. Moreover, to date, these diagnoses have not been addressed in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for MGFs. However, in most cases, the general principles have been included in the applicable NCCN Guidelines for each individual cancer site.
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External Validation of Generic and Cancer-Specific Risk Stratification Tools in Patients With Pulmonary Embolism and Active Cancer
Background: Numerous risk stratification tools exist to predict early post–pulmonary embolism (PE) mortality; however, few were specifically designed for use in patients with cancer. This study sought to evaluate the performance of 3 cancer-specific (RIETE, POMPE-C, and Font criteria) and 3 generic (Hestia, Pulmonary Embolism Severity Index [PESI], and Geneva prognostic score [GPS]) risk stratification tools for predicting 30-day post-PE mortality in patients with active cancer. Methods: We identified consecutive, adult, objectively confirmed patients with PE and active cancer presenting to our institution from November 2010 to January 2014. We calculated the proportion of patients categorized as low or high risk by each of the 6 risk stratification tools and determined each tools' accuracy for predicting 30-day all-cause mortality. Results: A total of 124 patients with PE and active cancer were included (mean age, 66.2 years; 46.0% with concurrent deep vein thrombosis; 49.2% with metastatic disease; and 46.8%, 16.9%, and 11.3% receiving chemotherapy, radiation, or both, respectively). Mortality at 30 days occurred in 25 patients (20.2%). The cancer-specific tools (POMPE-C, RIETE, and Font criteria) categorized between 32% and 43% of patients as low risk and displayed sensitivities and specificities of 88.0% to 96.0% and 38.4% to 52.5%, respectively. The generic PESI and Hestia tools had sensitivities >96.0%, but classified <19% of patients as low risk; specificity of these tools were low (PESI, 6.1%; Hestia, 23.2%). Although the final noncancer tool, GPS, classified 43.5% of patients as low risk, it did so with a sensitivity of 52.0% and specificity of 42.4%. Conclusions: When risk-stratifying PE in patients with active cancer, cancer-specific tools appeared to exhibit better prognostic accuracy than their generic counterparts. POMPE-C, RIETE, and the Font criteria identified a substantially greater proportion of patients with PE likely to survive to 30 days with comparable sensitivity to the generic tools.
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Radiosurgery for Brain Metastases: Changing Practice Patterns and Disparities in the United States
Background: Management of brain metastases typically includes radiotherapy (RT) with conventional fractionation and/or stereotactic radiosurgery (SRS). However, optimal indications and practice patterns for SRS remain unclear. We sought to evaluate national practice patterns for patients with metastatic disease receiving brain RT. Methods: We queried the National Cancer Data Base (NCDB) for patients diagnosed with metastatic non–small cell lung cancer, breast cancer, colorectal cancer, or melanoma from 2004 to 2014 who received upfront brain RT. Patients were divided into SRS and non-SRS cohorts. Patient and facility-level SRS predictors were analyzed with chi-square tests and logistic regression, and uptake trends were approximated with linear regression. Survival by diagnosis year was analyzed with the Kaplan-Meier method. Results: Of 75,953 patients, 12,250 (16.1%) received SRS and 63,703 (83.9%) received non-SRS. From 2004 to 2014, the proportion of patients receiving SRS annually increased (from 9.8% to 25.6%; P<.001), and the proportion of facilities using SRS annually increased (from 31.2% to 50.4%; P<.001). On multivariable analysis, nonwhite race, nonprivate insurance, and residence in lower-income or less-educated regions predicted lower SRS use (P<.05 for each). During the study period, SRS use increased disproportionally among patients with private insurance or who resided in higher-income or higher-educated regions. From 2004 to 2013, 1-year actuarial survival improved from 24.1% to 49.6% for patients selected for SRS and from 21.0% to 26.3% for non-SRS patients (P<.001). Conclusions: This NCDB analysis demonstrates steadily increasing—although modest overall—brain SRS use for patients with metastatic disease in the United States and identifies several progressively widening sociodemographic disparities in the adoption of SRS. Further research is needed to determine the reasons for these worsening disparities and their clinical implications on intracranial control, neurocognitive toxicities, quality of life, and survival for patients with brain metastases.
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Pazopanib Sensitivity in a Patient With Breast Cancer and FGFR1 Amplification
Treatment options for patients with hormone receptor–positive (HR+), HER2-negative (HER2–) breast cancer and resistance to endocrine therapy remain limited. An interesting therapeutic target in these patients is fibroblast growth factor receptor 1 (FGFR1). FGFR1 is amplified in approximately 11% of patients with breast cancer, especially those with HR+ disease. This report presents a patient with metastatic HR+ HER2– breast cancer harboring an FGFR1 amplification who was resistant to endocrine therapy but responded to pazopanib, a multi–tyrosine kinase inhibitor with FGFR-inhibiting activity. Upon pazopanib treatment, the patient's brain lesions nearly disappeared, and she experienced therapeutic changes in the lung and an improvement of liver function. This case suggests that pazopanib may be a promising agent for the treatment of patients with breast cancer and FGFR1 amplifications.
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Ensuring Patient Safety and Access in Cancer Care
The inability to obtain the right high-quality cancer care in a timely and safe manner can have devastating results for patients. As cancer care becomes inundated with cutting edge and novel treatments, such as personalized medicine, oral chemotherapy, biosimilars, and immunotherapy, new safety challenges are emerging at increasing speed and complexity. Moreover, shifting federal healthcare policies could have significant implications for the safety and access to high-quality and effective cancer care for millions of patients with cancer. Challenges and opportunities in ensuring patient access to safe, affordable, and high-quality cancer care remain significant within the policy landscape. To address these concerns, NCCN hosted the Ensuring Safety and Access in Cancer Care Policy Summit in June 2017 to discuss pertinent patient safety issues and access implications under the Trump administration, as well as policy and advocacy strategies to address these gaps and build on opportunities moving forward.
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A Patient Risk Model of Chemotherapy-Induced Febrile Neutropenia: Lessons Learned From the ANC Study Group
Neutropenia and its complications, including febrile neutropenia (FN), represent major toxicities associated with cancer chemotherapy, resulting in considerable morbidity, mortality, and costs. The myeloid growth factors such as granulocyte colony-stimulating factor (G-CSF) have been shown to reduce the risk of neutropenia complications while enabling safe and effective chemotherapy dose intensity. Concerns about the high costs of these agents along with limited physician adherence to clinical practice guidelines, resulting in both overuse and underuse, has stimulated interest in models for individual patient risk assessment to guide appropriate use of G-CSF. In a model developed and validated by the ANC Study Group, half of patients were classified as high risk and half as low risk based on patient-, disease-, and treatment-related factors. This model has been further validated in an independent patient population. Physician-assessed risk of FN, as well as the decision to use prophylactic CSF, has been shown to correlate poorly with the FN risk estimated by the model. Additional modeling efforts in both adults and children receiving cancer treatment have been reported. Identification of patients at a high individual risk for FN and its consequences may offer the potential for optimal chemotherapy delivery and patient outcomes. Likewise, identification of patients at low risk for neutropenic events may reduce costs when such supportive care is not warranted. This article reviews and summarizes FN modeling studies and the opportunities for personalizing supportive care in patients receiving chemotherapy.
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NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 3.2017
The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provide recommendations for the management of patients with high-risk syndromes associated with an increased risk of colorectal cancer (CRC). The NCCN Panel for Genetic/Familial High-Risk Assessment: Colorectal meets at least annually to assess comments from reviewers within their institutions, examine relevant data, and reevaluate and update their recommendations. These NCCN Guidelines Insights focus on genes newly associated with CRC risk on multigene panels, the associated evidence, and currently recommended management strategies.
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Myeloid Growth Factors, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology
Myeloid growth factors (MGFs) are given as supportive care to patients receiving myelosuppressive chemotherapy to reduce the incidence of neutropenia. This selection from the NCCN Guidelines for MGFs focuses on the evaluation of regimen- and patient-specific risk factors for the development of febrile neutropenia (FN), the prophylactic use of MGFs for the prevention of chemotherapy-induced FN, and assessing the risks and benefits of MGF use in clinical practice.
http://ift.tt/2kgYE47
KRAS Testing, Tumor Location, and Survival in Patients With Stage IV Colorectal Cancer: SEER 2010-2013
Purpose: KRAS mutations and tumor location have been associated with response to targeted therapy among patients with stage IV colorectal cancer (CRC) in various trials. This study performed the first population-based examination of associations between KRAS mutations, tumor location, and survival, and assessed factors associated with documented KRAS testing. Methods: Patients with stage IV adenocarcinoma of the colon/rectum diagnosed from 2010 to 2013 were extracted from SEER data. Analyses of patient characteristics, KRAS testing, and tumor location were conducted using logistic regression. Cox proportional hazards models assessed relationships between KRAS mutations, tumor location, and risk of all-cause death. Results: Of 22,542 patients, 30% received KRAS testing, and 44% of these had mutations. Those tested tended to be younger, married, and metropolitan area residents, and have private insurance or Medicare. Rates of KRAS testing also varied by registry (range, 20%–46%). Patients with right-sided colon cancer (vs left-sided) tended to be older, female, and black; have mucinous, KRAS-mutant tumors; and have a greater risk of death (hazard ratio [HR], 1.27; 95% CI, 1.22–1.32). KRAS mutations were not associated with greater risk of death in the overall population; however, they were associated with greater risk of death among patients with left-sided colon cancer (HR, 1.19; 95% CI, 1.05–1.33). Conclusions: This large population-based study showed that among patients initially diagnosed with stage IV CRC, right-sided colon cancer was associated with greater risk of death compared with left-sided cancer, and KRAS mutations were only associated with risk of death in left-sided colon cancer. An unexpected finding was that among patients with stage IV disease, right-sided cancer was more commonly seen in black patients versus whites. Future studies should further explore these associations and determine the role of biology versus treatment differences. In addition, use of KRAS testing is increasing, but there is wide geographic variation wherein disparities related to insurance coverage and rurality may warrant further study.
http://ift.tt/2jCbHh2
Prevalence of Physical Problems Detected by the Distress Thermometer and Problem List in Patients With Myeloproliferative Disorders
Background: Patients with myeloproliferative neoplasms (MPNs) can have a severe physical symptom burden over an extended disease trajectory that contributes to decreased quality of life. Few studies, however, have characterized which patients most frequently consider physical symptoms a problem. This study describes the physical symptoms of patients with MPNs and the relationship of these symptoms to patient characteristics. Methods: Patients with MPNs (N=117) completed questionnaires in a dedicated academic medical center MPN clinic. Patients reported demographics (age, race/ethnicity, sex, marital status, employment status), disease characteristics (MPN type, time with MPN), and whether they were bothered by any of 22 variables in the "Physical Problems" list in the Distress Thermometer and Problem List (DT&PL). Results: The median number of physical problems endorsed by patients was 2 (median, 2.26; SD, 3.18), with a range from 0 to 20. Two-fifths endorsed no physical problems, one-fifth endorsed 1 problem, and two-fifths endorsed ≥2 problems, with fatigue (35.5%), sleep (27.1%), pain (21.5%), dry skin/pruritus (18.7%), and memory/concentration (16.8%) being the most commonly reported. Non-Caucasian participants reported more problems with sleep (P=.050), pain (P=.016), and tingling (P=.026). Patients with polycythemia vera (PV) reported more issues with tingling (P=.046) and sexual problems (P=.032). Conclusions: Patients with MPNs are more likely to report physical symptom bother than to report no bother with multiple physical problems on the DT&PL. Patients of minority race/ethnicity and those with PV, however, showed heightened prevalence of physical problems—characteristics which may be used to triage patients for more intensive symptom management.
http://ift.tt/2jCgPBI
Controversies Regarding Use of Myeloid Growth Factors in Leukemia
This review focuses on the data supporting the use of myeloid growth factors (MGFs) in patients being treated for acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and hairy cell leukemia, for which neutropenia is a common complication of treatment. However, due to the lack of randomized trial data or conflicting results of clinical studies, comprehensive guidelines have been difficult to formulate. Moreover, to date, these diagnoses have not been addressed in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for MGFs. However, in most cases, the general principles have been included in the applicable NCCN Guidelines for each individual cancer site.
http://ift.tt/2jCG1Z0
External Validation of Generic and Cancer-Specific Risk Stratification Tools in Patients With Pulmonary Embolism and Active Cancer
Background: Numerous risk stratification tools exist to predict early post–pulmonary embolism (PE) mortality; however, few were specifically designed for use in patients with cancer. This study sought to evaluate the performance of 3 cancer-specific (RIETE, POMPE-C, and Font criteria) and 3 generic (Hestia, Pulmonary Embolism Severity Index [PESI], and Geneva prognostic score [GPS]) risk stratification tools for predicting 30-day post-PE mortality in patients with active cancer. Methods: We identified consecutive, adult, objectively confirmed patients with PE and active cancer presenting to our institution from November 2010 to January 2014. We calculated the proportion of patients categorized as low or high risk by each of the 6 risk stratification tools and determined each tools' accuracy for predicting 30-day all-cause mortality. Results: A total of 124 patients with PE and active cancer were included (mean age, 66.2 years; 46.0% with concurrent deep vein thrombosis; 49.2% with metastatic disease; and 46.8%, 16.9%, and 11.3% receiving chemotherapy, radiation, or both, respectively). Mortality at 30 days occurred in 25 patients (20.2%). The cancer-specific tools (POMPE-C, RIETE, and Font criteria) categorized between 32% and 43% of patients as low risk and displayed sensitivities and specificities of 88.0% to 96.0% and 38.4% to 52.5%, respectively. The generic PESI and Hestia tools had sensitivities >96.0%, but classified <19% of patients as low risk; specificity of these tools were low (PESI, 6.1%; Hestia, 23.2%). Although the final noncancer tool, GPS, classified 43.5% of patients as low risk, it did so with a sensitivity of 52.0% and specificity of 42.4%. Conclusions: When risk-stratifying PE in patients with active cancer, cancer-specific tools appeared to exhibit better prognostic accuracy than their generic counterparts. POMPE-C, RIETE, and the Font criteria identified a substantially greater proportion of patients with PE likely to survive to 30 days with comparable sensitivity to the generic tools.
http://ift.tt/2jCFXbI
Radiosurgery for Brain Metastases: Changing Practice Patterns and Disparities in the United States
Background: Management of brain metastases typically includes radiotherapy (RT) with conventional fractionation and/or stereotactic radiosurgery (SRS). However, optimal indications and practice patterns for SRS remain unclear. We sought to evaluate national practice patterns for patients with metastatic disease receiving brain RT. Methods: We queried the National Cancer Data Base (NCDB) for patients diagnosed with metastatic non–small cell lung cancer, breast cancer, colorectal cancer, or melanoma from 2004 to 2014 who received upfront brain RT. Patients were divided into SRS and non-SRS cohorts. Patient and facility-level SRS predictors were analyzed with chi-square tests and logistic regression, and uptake trends were approximated with linear regression. Survival by diagnosis year was analyzed with the Kaplan-Meier method. Results: Of 75,953 patients, 12,250 (16.1%) received SRS and 63,703 (83.9%) received non-SRS. From 2004 to 2014, the proportion of patients receiving SRS annually increased (from 9.8% to 25.6%; P<.001), and the proportion of facilities using SRS annually increased (from 31.2% to 50.4%; P<.001). On multivariable analysis, nonwhite race, nonprivate insurance, and residence in lower-income or less-educated regions predicted lower SRS use (P<.05 for each). During the study period, SRS use increased disproportionally among patients with private insurance or who resided in higher-income or higher-educated regions. From 2004 to 2013, 1-year actuarial survival improved from 24.1% to 49.6% for patients selected for SRS and from 21.0% to 26.3% for non-SRS patients (P<.001). Conclusions: This NCDB analysis demonstrates steadily increasing—although modest overall—brain SRS use for patients with metastatic disease in the United States and identifies several progressively widening sociodemographic disparities in the adoption of SRS. Further research is needed to determine the reasons for these worsening disparities and their clinical implications on intracranial control, neurocognitive toxicities, quality of life, and survival for patients with brain metastases.
http://ift.tt/2jCFSoq
Pazopanib Sensitivity in a Patient With Breast Cancer and FGFR1 Amplification
Treatment options for patients with hormone receptor–positive (HR+), HER2-negative (HER2–) breast cancer and resistance to endocrine therapy remain limited. An interesting therapeutic target in these patients is fibroblast growth factor receptor 1 (FGFR1). FGFR1 is amplified in approximately 11% of patients with breast cancer, especially those with HR+ disease. This report presents a patient with metastatic HR+ HER2– breast cancer harboring an FGFR1 amplification who was resistant to endocrine therapy but responded to pazopanib, a multi–tyrosine kinase inhibitor with FGFR-inhibiting activity. Upon pazopanib treatment, the patient's brain lesions nearly disappeared, and she experienced therapeutic changes in the lung and an improvement of liver function. This case suggests that pazopanib may be a promising agent for the treatment of patients with breast cancer and FGFR1 amplifications.
http://ift.tt/2kgcO5q
Geographic Variation of Adjuvant Breast Cancer Therapy Initiation in the United States: Lessons From Medicare Part D
Background: Drug utilization under Medicare Part D varies significantly by geographic region. This study examined the extent to which geographic variation in Part D plan characteristics contributes to the variation in choice of initial endocrine therapy agent among women with incident breast cancer. Methods: Two-stage multivariate regression analyses were applied to the 16,541 women identified from Medicare claims as having incident breast cancer in 2006–2007. The first stage determined the effect of state of residence on the probability of having an aromatase inhibitor (AI), as opposed to tamoxifen, as initial endocrine therapy. The second stage provided estimates of the impact of state-specific Part D plan characteristics on variation in choice of initial therapy. Results: There was substantial residual geographic variation in the likelihood of using an AI as initial endocrine therapy, despite controlling for socioeconomic status, breast cancer treatment, and other factors. Regression-adjusted probabilities of starting an AI ranged from 57.3% in Wyoming to 92.6% in the District of Columbia. Results from the second stage revealed that variation in characteristics of Part D plans across states explained approximately one-third (30%) of the state-level variability in endocrine therapy. A higher number of plans with cost-sharing above the mean, greater spread in deductibles, and a greater spread in monthly drug premiums were associated with lower adjusted state probabilities of initiating an AI. In contrast, a higher number of drug plans with monthly premiums above the state mean and higher mean cost-sharing (in dollars) were both positively associated with likelihood of starting on an AI. Conclusions: Study findings suggest that variation in benefit design of Part D plans accounts for an important share of the large and persisting variability in use of AIs—the preferred oral therapy for breast cancer.
http://ift.tt/2jDBp4L
Ensuring Patient Safety and Access in Cancer Care
The inability to obtain the right high-quality cancer care in a timely and safe manner can have devastating results for patients. As cancer care becomes inundated with cutting edge and novel treatments, such as personalized medicine, oral chemotherapy, biosimilars, and immunotherapy, new safety challenges are emerging at increasing speed and complexity. Moreover, shifting federal healthcare policies could have significant implications for the safety and access to high-quality and effective cancer care for millions of patients with cancer. Challenges and opportunities in ensuring patient access to safe, affordable, and high-quality cancer care remain significant within the policy landscape. To address these concerns, NCCN hosted the Ensuring Safety and Access in Cancer Care Policy Summit in June 2017 to discuss pertinent patient safety issues and access implications under the Trump administration, as well as policy and advocacy strategies to address these gaps and build on opportunities moving forward.
http://ift.tt/2kgcJi8
A Patient Risk Model of Chemotherapy-Induced Febrile Neutropenia: Lessons Learned From the ANC Study Group
Neutropenia and its complications, including febrile neutropenia (FN), represent major toxicities associated with cancer chemotherapy, resulting in considerable morbidity, mortality, and costs. The myeloid growth factors such as granulocyte colony-stimulating factor (G-CSF) have been shown to reduce the risk of neutropenia complications while enabling safe and effective chemotherapy dose intensity. Concerns about the high costs of these agents along with limited physician adherence to clinical practice guidelines, resulting in both overuse and underuse, has stimulated interest in models for individual patient risk assessment to guide appropriate use of G-CSF. In a model developed and validated by the ANC Study Group, half of patients were classified as high risk and half as low risk based on patient-, disease-, and treatment-related factors. This model has been further validated in an independent patient population. Physician-assessed risk of FN, as well as the decision to use prophylactic CSF, has been shown to correlate poorly with the FN risk estimated by the model. Additional modeling efforts in both adults and children receiving cancer treatment have been reported. Identification of patients at a high individual risk for FN and its consequences may offer the potential for optimal chemotherapy delivery and patient outcomes. Likewise, identification of patients at low risk for neutropenic events may reduce costs when such supportive care is not warranted. This article reviews and summarizes FN modeling studies and the opportunities for personalizing supportive care in patients receiving chemotherapy.
http://ift.tt/2jCFOVI
NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 3.2017
The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provide recommendations for the management of patients with high-risk syndromes associated with an increased risk of colorectal cancer (CRC). The NCCN Panel for Genetic/Familial High-Risk Assessment: Colorectal meets at least annually to assess comments from reviewers within their institutions, examine relevant data, and reevaluate and update their recommendations. These NCCN Guidelines Insights focus on genes newly associated with CRC risk on multigene panels, the associated evidence, and currently recommended management strategies.
http://ift.tt/2khlSHd
Comparison of radiation therapy modalities for hepatocellular carcinoma with portal vein thrombosis: A meta-analysis and systematic review
We performed a meta-analysis and systematic review to compare the radiotherapy (RT) modalities for hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT).
http://ift.tt/2BnPvlj
Cancer Immunotherapy in a Neglected Population: The Current Use and Future of T-cell-Mediated Checkpoint Inhibitors in Organ Transplant Patients
Source:Cancer Treatment Reviews
Author(s): Young Kwang Chae, Carlos Galvez, Jonathan F. Anker, Wade T. Iams, Manali Bhave
Although the indications for immune checkpoint inhibitors continue to grow, organ transplant recipients with advanced malignancies have been largely excluded from clinical trials testing the safety and efficacy of these therapies given their need for chronic immunosuppression and the risk of allograft rejection. With the rapid growth of transplant medicine and the increased risk of malignancy associated with chronic immunosuppression, it is critical that we systematically analyze the available data describing immune checkpoint blockade in the organ transplant population. Herein we provide a current and comprehensive review of cases in which immune checkpoint blockade was used on organ transplant recipients. Furthermore, we discuss the differences in efficacy and risk of allograft rejection between CTLA-4 and PD-1 inhibitors and make recommendations based on the limited available clinical data. We also discuss the future of immune checkpoint blockade in this subpopulation and explore the emerging data of promising combination therapies with mTOR, BRAF/MEK, and BTK/ITK inhibitors. Further clinical experience and larger clinical trials involving immune checkpoint inhibitors, whether as monotherapies or combinatorial therapies, will help develop regimens that optimize anti-tumor response and minimize the risk of allograft rejection in organ transplant patients.
http://ift.tt/2yUc3aT
American Journal of Cancer Research; +19 new citations
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Expanding the use of abiraterone in prostate cancer: Is earlier always better?
Expanding the use of abiraterone in prostate cancer: Is earlier always better?
Cancer Biol Ther. 2017 Dec 08;:1-4
Authors: Schmidt KT, Madan RA, Figg WD
PMID: 29219670 [PubMed - as supplied by publisher]
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Multispectral imaging reveals hyper active TGF-β signaling in colorectal cancer.
Multispectral imaging reveals hyper active TGF-β signaling in colorectal cancer.
Cancer Biol Ther. 2017 Dec 08;:1-8
Authors: Yang L, Liu Z, Tan J, Dong H, Zhang X
Abstract
Advances in multiplex immunohistochemistry (IHC) techniques and digital pathology platforms allow quantification of multiple proteins at same tissue section and produce continuous data. TGF-β signaling plays crucial and complex roles in colorectal cancer (CRC). We here aimed to investigate clinical pathological relevant of proteins involved in TGF-β signaling at CRC tissues. Multiplex fluorescent IHC was used to quantitative analysis. The levels of eight proteins (TGF-β1, TGFBRI, TGFBRII, SMAD4, SMAD2/3, p-SMAD2/3, SMAD1/5/9, and p-SMAD1/5/9) were determined in TMA sections. Quantitative analysis was carried out by a scoring system by InForm software. It revealed that TGF-β signaling was hyper active. The levels of TGF-β1, TGFBRI, TGFBRII, SMAD4, SMAD1/5/9 and p-SMAD2/3 were significantly increased in cancer tissues when compared their levels in normal tissues. Furthermore, the levels of eight proteins in stroma were significantly lower than the levels that in cancer tissues. Clinical pathological relevant analysis exhibited that TGF-β signaling inclined to suppress the progression of tumor. SMAD1/5/9, TGFBRII, SMAD2/3 were confirmed as significant predictors for overall survival. In conclusion, we established a method based on multispectral imaging to extensively explore the clinical relevant of TGF-β signaling proteins. These results provided an opportunity to consider the novel application for proteins involving TGF-β signaling that used as diagnostic or prognostic biomarkers to conduct tumor therapy.
PMID: 29219668 [PubMed - as supplied by publisher]
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The levels of mutant K-RAS and mutant N-RAS are rapidly reduced in a Beclin1 / ATG5 -dependent fashion by the irreversible ERBB1/2/4 inhibitor neratinib.
The levels of mutant K-RAS and mutant N-RAS are rapidly reduced in a Beclin1 / ATG5 -dependent fashion by the irreversible ERBB1/2/4 inhibitor neratinib.
Cancer Biol Ther. 2017 Dec 08;:1-6
Authors: Booth L, Roberts JL, Poklepovic A, Kirkwood J, Sander C, Avogadri-Connors F, Cutler RE, Lalani AS, Dent P
Abstract
The FDA approved irreversible inhibitor of ERBB1/2/4, neratinib, was recently shown to rapidly down-regulate the expression of ERBB1/2/4 as well as the levels of c-MET and mutant K-RAS via autophagic degradation. In the present studies, in a dose-dependent fashion, neratinib reduced the expression levels of mutant K-RAS or of mutant N-RAS, which was augmented in an additive to greater than additive fashion by the HDAC inhibitors sodium valproate and AR42. Neratinib could reduce PDGFRα levels in GBM cells, that was enhanced by sodium valproate. Knock down of Beclin1 or of ATG5 prevented neratinib and neratinib combined with sodium valproate / AR42 from reducing the expression of mutant N-RAS in established PDX and fresh PDX models of ovarian cancer and melanoma, respectively. Neratinib and the drug combinations caused the co-localization of mutant RAS proteins and ERBB2 with Beclin1 and cathepsin B. The drug combination activated the AMP-dependent protein kinase that was causal in enhancing HMG Co A reductase phosphorylation. Collectively, our data reinforce the concept that the irreversible ERBB1/2/4 inhibitor neratinib has the potential for use in the treatment of tumors expressing mutant RAS proteins.
PMID: 29219657 [PubMed - as supplied by publisher]
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Modulating secreted components of tumor microenvironment: A masterstroke in tumor therapeutics.
Modulating secreted components of tumor microenvironment: A masterstroke in tumor therapeutics.
Cancer Biol Ther. 2017 Dec 08;:1-10
Authors: Patel H, Nilendu P, Jahagirdar D, Pal JK, Sharma NK
Abstract
The microenvironment in which cancer resides plays an important role in regulating cancer survival, progression, malignancy and drug resistance. Tumor microenvironment (TME) consists of heterogeneous number and types of cellular and non-cellular components that vary in relation to tumor phenotype and genotype. In recent, non-cellular secreted components of microenvironmental heterogeneity have been suggested to contain various growth factors, cytokines, RNA, DNA, metabolites, structural matrix and matricellular proteins. These non-cellular components have been indicated to orchestrate numerous ways to support cancer survival and progression by providing metabolites, energy, growth signals, evading immune surveillance, drug resistance environment, metastatic and angiogenesis cues. Thus, switching action from pro-cancer to anti-cancer activities of these secreted components of TME has been considered as a new avenue in cancer therapeutics and drug resistance. In this report, we summarize the recent pre-clinical and clinical evidences to emphasize the importance of non-cellular components of TME in achieving precision therapeutics and biomarker study.
PMID: 29219656 [PubMed - as supplied by publisher]
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Expanding the use of abiraterone in prostate cancer: Is earlier always better?
Expanding the use of abiraterone in prostate cancer: Is earlier always better?
Cancer Biol Ther. 2017 Dec 08;:1-4
Authors: Schmidt KT, Madan RA, Figg WD
PMID: 29219670 [PubMed - as supplied by publisher]
http://ift.tt/2BmVyGB
Multispectral imaging reveals hyper active TGF-β signaling in colorectal cancer.
Multispectral imaging reveals hyper active TGF-β signaling in colorectal cancer.
Cancer Biol Ther. 2017 Dec 08;:1-8
Authors: Yang L, Liu Z, Tan J, Dong H, Zhang X
Abstract
Advances in multiplex immunohistochemistry (IHC) techniques and digital pathology platforms allow quantification of multiple proteins at same tissue section and produce continuous data. TGF-β signaling plays crucial and complex roles in colorectal cancer (CRC). We here aimed to investigate clinical pathological relevant of proteins involved in TGF-β signaling at CRC tissues. Multiplex fluorescent IHC was used to quantitative analysis. The levels of eight proteins (TGF-β1, TGFBRI, TGFBRII, SMAD4, SMAD2/3, p-SMAD2/3, SMAD1/5/9, and p-SMAD1/5/9) were determined in TMA sections. Quantitative analysis was carried out by a scoring system by InForm software. It revealed that TGF-β signaling was hyper active. The levels of TGF-β1, TGFBRI, TGFBRII, SMAD4, SMAD1/5/9 and p-SMAD2/3 were significantly increased in cancer tissues when compared their levels in normal tissues. Furthermore, the levels of eight proteins in stroma were significantly lower than the levels that in cancer tissues. Clinical pathological relevant analysis exhibited that TGF-β signaling inclined to suppress the progression of tumor. SMAD1/5/9, TGFBRII, SMAD2/3 were confirmed as significant predictors for overall survival. In conclusion, we established a method based on multispectral imaging to extensively explore the clinical relevant of TGF-β signaling proteins. These results provided an opportunity to consider the novel application for proteins involving TGF-β signaling that used as diagnostic or prognostic biomarkers to conduct tumor therapy.
PMID: 29219668 [PubMed - as supplied by publisher]
http://ift.tt/2AQhmJZ
The levels of mutant K-RAS and mutant N-RAS are rapidly reduced in a Beclin1 / ATG5 -dependent fashion by the irreversible ERBB1/2/4 inhibitor neratinib.
The levels of mutant K-RAS and mutant N-RAS are rapidly reduced in a Beclin1 / ATG5 -dependent fashion by the irreversible ERBB1/2/4 inhibitor neratinib.
Cancer Biol Ther. 2017 Dec 08;:1-6
Authors: Booth L, Roberts JL, Poklepovic A, Kirkwood J, Sander C, Avogadri-Connors F, Cutler RE, Lalani AS, Dent P
Abstract
The FDA approved irreversible inhibitor of ERBB1/2/4, neratinib, was recently shown to rapidly down-regulate the expression of ERBB1/2/4 as well as the levels of c-MET and mutant K-RAS via autophagic degradation. In the present studies, in a dose-dependent fashion, neratinib reduced the expression levels of mutant K-RAS or of mutant N-RAS, which was augmented in an additive to greater than additive fashion by the HDAC inhibitors sodium valproate and AR42. Neratinib could reduce PDGFRα levels in GBM cells, that was enhanced by sodium valproate. Knock down of Beclin1 or of ATG5 prevented neratinib and neratinib combined with sodium valproate / AR42 from reducing the expression of mutant N-RAS in established PDX and fresh PDX models of ovarian cancer and melanoma, respectively. Neratinib and the drug combinations caused the co-localization of mutant RAS proteins and ERBB2 with Beclin1 and cathepsin B. The drug combination activated the AMP-dependent protein kinase that was causal in enhancing HMG Co A reductase phosphorylation. Collectively, our data reinforce the concept that the irreversible ERBB1/2/4 inhibitor neratinib has the potential for use in the treatment of tumors expressing mutant RAS proteins.
PMID: 29219657 [PubMed - as supplied by publisher]
http://ift.tt/2C12gPW
Modulating secreted components of tumor microenvironment: A masterstroke in tumor therapeutics.
Modulating secreted components of tumor microenvironment: A masterstroke in tumor therapeutics.
Cancer Biol Ther. 2017 Dec 08;:1-10
Authors: Patel H, Nilendu P, Jahagirdar D, Pal JK, Sharma NK
Abstract
The microenvironment in which cancer resides plays an important role in regulating cancer survival, progression, malignancy and drug resistance. Tumor microenvironment (TME) consists of heterogeneous number and types of cellular and non-cellular components that vary in relation to tumor phenotype and genotype. In recent, non-cellular secreted components of microenvironmental heterogeneity have been suggested to contain various growth factors, cytokines, RNA, DNA, metabolites, structural matrix and matricellular proteins. These non-cellular components have been indicated to orchestrate numerous ways to support cancer survival and progression by providing metabolites, energy, growth signals, evading immune surveillance, drug resistance environment, metastatic and angiogenesis cues. Thus, switching action from pro-cancer to anti-cancer activities of these secreted components of TME has been considered as a new avenue in cancer therapeutics and drug resistance. In this report, we summarize the recent pre-clinical and clinical evidences to emphasize the importance of non-cellular components of TME in achieving precision therapeutics and biomarker study.
PMID: 29219656 [PubMed - as supplied by publisher]
http://ift.tt/2Bn7gRK
Expanding the use of abiraterone in prostate cancer: Is earlier always better?
Expanding the use of abiraterone in prostate cancer: Is earlier always better?
Cancer Biol Ther. 2017 Dec 08;:1-4
Authors: Schmidt KT, Madan RA, Figg WD
PMID: 29219670 [PubMed - as supplied by publisher]
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Multispectral imaging reveals hyper active TGF-β signaling in colorectal cancer.
Multispectral imaging reveals hyper active TGF-β signaling in colorectal cancer.
Cancer Biol Ther. 2017 Dec 08;:1-8
Authors: Yang L, Liu Z, Tan J, Dong H, Zhang X
Abstract
Advances in multiplex immunohistochemistry (IHC) techniques and digital pathology platforms allow quantification of multiple proteins at same tissue section and produce continuous data. TGF-β signaling plays crucial and complex roles in colorectal cancer (CRC). We here aimed to investigate clinical pathological relevant of proteins involved in TGF-β signaling at CRC tissues. Multiplex fluorescent IHC was used to quantitative analysis. The levels of eight proteins (TGF-β1, TGFBRI, TGFBRII, SMAD4, SMAD2/3, p-SMAD2/3, SMAD1/5/9, and p-SMAD1/5/9) were determined in TMA sections. Quantitative analysis was carried out by a scoring system by InForm software. It revealed that TGF-β signaling was hyper active. The levels of TGF-β1, TGFBRI, TGFBRII, SMAD4, SMAD1/5/9 and p-SMAD2/3 were significantly increased in cancer tissues when compared their levels in normal tissues. Furthermore, the levels of eight proteins in stroma were significantly lower than the levels that in cancer tissues. Clinical pathological relevant analysis exhibited that TGF-β signaling inclined to suppress the progression of tumor. SMAD1/5/9, TGFBRII, SMAD2/3 were confirmed as significant predictors for overall survival. In conclusion, we established a method based on multispectral imaging to extensively explore the clinical relevant of TGF-β signaling proteins. These results provided an opportunity to consider the novel application for proteins involving TGF-β signaling that used as diagnostic or prognostic biomarkers to conduct tumor therapy.
PMID: 29219668 [PubMed - as supplied by publisher]
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The levels of mutant K-RAS and mutant N-RAS are rapidly reduced in a Beclin1 / ATG5 -dependent fashion by the irreversible ERBB1/2/4 inhibitor neratinib.
The levels of mutant K-RAS and mutant N-RAS are rapidly reduced in a Beclin1 / ATG5 -dependent fashion by the irreversible ERBB1/2/4 inhibitor neratinib.
Cancer Biol Ther. 2017 Dec 08;:1-6
Authors: Booth L, Roberts JL, Poklepovic A, Kirkwood J, Sander C, Avogadri-Connors F, Cutler RE, Lalani AS, Dent P
Abstract
The FDA approved irreversible inhibitor of ERBB1/2/4, neratinib, was recently shown to rapidly down-regulate the expression of ERBB1/2/4 as well as the levels of c-MET and mutant K-RAS via autophagic degradation. In the present studies, in a dose-dependent fashion, neratinib reduced the expression levels of mutant K-RAS or of mutant N-RAS, which was augmented in an additive to greater than additive fashion by the HDAC inhibitors sodium valproate and AR42. Neratinib could reduce PDGFRα levels in GBM cells, that was enhanced by sodium valproate. Knock down of Beclin1 or of ATG5 prevented neratinib and neratinib combined with sodium valproate / AR42 from reducing the expression of mutant N-RAS in established PDX and fresh PDX models of ovarian cancer and melanoma, respectively. Neratinib and the drug combinations caused the co-localization of mutant RAS proteins and ERBB2 with Beclin1 and cathepsin B. The drug combination activated the AMP-dependent protein kinase that was causal in enhancing HMG Co A reductase phosphorylation. Collectively, our data reinforce the concept that the irreversible ERBB1/2/4 inhibitor neratinib has the potential for use in the treatment of tumors expressing mutant RAS proteins.
PMID: 29219657 [PubMed - as supplied by publisher]
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Modulating secreted components of tumor microenvironment: A masterstroke in tumor therapeutics.
Modulating secreted components of tumor microenvironment: A masterstroke in tumor therapeutics.
Cancer Biol Ther. 2017 Dec 08;:1-10
Authors: Patel H, Nilendu P, Jahagirdar D, Pal JK, Sharma NK
Abstract
The microenvironment in which cancer resides plays an important role in regulating cancer survival, progression, malignancy and drug resistance. Tumor microenvironment (TME) consists of heterogeneous number and types of cellular and non-cellular components that vary in relation to tumor phenotype and genotype. In recent, non-cellular secreted components of microenvironmental heterogeneity have been suggested to contain various growth factors, cytokines, RNA, DNA, metabolites, structural matrix and matricellular proteins. These non-cellular components have been indicated to orchestrate numerous ways to support cancer survival and progression by providing metabolites, energy, growth signals, evading immune surveillance, drug resistance environment, metastatic and angiogenesis cues. Thus, switching action from pro-cancer to anti-cancer activities of these secreted components of TME has been considered as a new avenue in cancer therapeutics and drug resistance. In this report, we summarize the recent pre-clinical and clinical evidences to emphasize the importance of non-cellular components of TME in achieving precision therapeutics and biomarker study.
PMID: 29219656 [PubMed - as supplied by publisher]
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[Gut microbiota: What impact on colorectal carcinogenesis and treatment?]
| Related Articles |
[Gut microbiota: What impact on colorectal carcinogenesis and treatment?]
Bull Cancer. 2017 Dec 04;:
Authors: Bruneau A, Baylatry MT, Joly AC, Sokol H
Abstract
The gut microbiota, composed of 1014 microorganisms, is now considered as a "hidden organ", regarding to its digestive, metabolic and immune functions, which are helpful to its host. For the last 15 years, advances in molecular biology have highlighted the association of gut microbiota dysbiosis with several diseases, including colorectal cancer. An increased abundance of some bacteria (including Fusobacterium nucleatum, Bacteroides fragilis, Escherichia coli) is associated with cancer, whereas others seem to be protective (Faecalibacterium prausnitzii). Several mechanisms, which are species-specific, are involved in colorectal carcinogenesis. Most of the time, bacterial toxins are involved in pro-inflammatory processes and in activation of angiogenesis and cellular proliferation pathways. The identification of these bacteria leads to envisage the gut microbiota as potential screening tool for colorectal cancer. Recent studies showed a relation between the gut microbiota and the efficacy and toxicity of chemotherapies (oxaliplatin, irinotecan) and immunotherapies (including ipilimumab). Therapeutic approaches targeting the gut microbiota are now available (probiotics, fecal microbiota transplantation…). New therapeutic strategy combining both chemotherapy and/or immunotherapy with an adjuvant treatment targeting the gut microbiota can now be developed in order to improve treatment response and tolerance.
PMID: 29217301 [PubMed - as supplied by publisher]
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Expanding the use of abiraterone in prostate cancer: Is earlier always better?
Expanding the use of abiraterone in prostate cancer: Is earlier always better?
Cancer Biol Ther. 2017 Dec 08;:1-4
Authors: Schmidt KT, Madan RA, Figg WD
PMID: 29219670 [PubMed - as supplied by publisher]
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Multispectral imaging reveals hyper active TGF-β signaling in colorectal cancer.
Multispectral imaging reveals hyper active TGF-β signaling in colorectal cancer.
Cancer Biol Ther. 2017 Dec 08;:1-8
Authors: Yang L, Liu Z, Tan J, Dong H, Zhang X
Abstract
Advances in multiplex immunohistochemistry (IHC) techniques and digital pathology platforms allow quantification of multiple proteins at same tissue section and produce continuous data. TGF-β signaling plays crucial and complex roles in colorectal cancer (CRC). We here aimed to investigate clinical pathological relevant of proteins involved in TGF-β signaling at CRC tissues. Multiplex fluorescent IHC was used to quantitative analysis. The levels of eight proteins (TGF-β1, TGFBRI, TGFBRII, SMAD4, SMAD2/3, p-SMAD2/3, SMAD1/5/9, and p-SMAD1/5/9) were determined in TMA sections. Quantitative analysis was carried out by a scoring system by InForm software. It revealed that TGF-β signaling was hyper active. The levels of TGF-β1, TGFBRI, TGFBRII, SMAD4, SMAD1/5/9 and p-SMAD2/3 were significantly increased in cancer tissues when compared their levels in normal tissues. Furthermore, the levels of eight proteins in stroma were significantly lower than the levels that in cancer tissues. Clinical pathological relevant analysis exhibited that TGF-β signaling inclined to suppress the progression of tumor. SMAD1/5/9, TGFBRII, SMAD2/3 were confirmed as significant predictors for overall survival. In conclusion, we established a method based on multispectral imaging to extensively explore the clinical relevant of TGF-β signaling proteins. These results provided an opportunity to consider the novel application for proteins involving TGF-β signaling that used as diagnostic or prognostic biomarkers to conduct tumor therapy.
PMID: 29219668 [PubMed - as supplied by publisher]
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The levels of mutant K-RAS and mutant N-RAS are rapidly reduced in a Beclin1 / ATG5 -dependent fashion by the irreversible ERBB1/2/4 inhibitor neratinib.
The levels of mutant K-RAS and mutant N-RAS are rapidly reduced in a Beclin1 / ATG5 -dependent fashion by the irreversible ERBB1/2/4 inhibitor neratinib.
Cancer Biol Ther. 2017 Dec 08;:1-6
Authors: Booth L, Roberts JL, Poklepovic A, Kirkwood J, Sander C, Avogadri-Connors F, Cutler RE, Lalani AS, Dent P
Abstract
The FDA approved irreversible inhibitor of ERBB1/2/4, neratinib, was recently shown to rapidly down-regulate the expression of ERBB1/2/4 as well as the levels of c-MET and mutant K-RAS via autophagic degradation. In the present studies, in a dose-dependent fashion, neratinib reduced the expression levels of mutant K-RAS or of mutant N-RAS, which was augmented in an additive to greater than additive fashion by the HDAC inhibitors sodium valproate and AR42. Neratinib could reduce PDGFRα levels in GBM cells, that was enhanced by sodium valproate. Knock down of Beclin1 or of ATG5 prevented neratinib and neratinib combined with sodium valproate / AR42 from reducing the expression of mutant N-RAS in established PDX and fresh PDX models of ovarian cancer and melanoma, respectively. Neratinib and the drug combinations caused the co-localization of mutant RAS proteins and ERBB2 with Beclin1 and cathepsin B. The drug combination activated the AMP-dependent protein kinase that was causal in enhancing HMG Co A reductase phosphorylation. Collectively, our data reinforce the concept that the irreversible ERBB1/2/4 inhibitor neratinib has the potential for use in the treatment of tumors expressing mutant RAS proteins.
PMID: 29219657 [PubMed - as supplied by publisher]
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Modulating secreted components of tumor microenvironment: A masterstroke in tumor therapeutics.
Modulating secreted components of tumor microenvironment: A masterstroke in tumor therapeutics.
Cancer Biol Ther. 2017 Dec 08;:1-10
Authors: Patel H, Nilendu P, Jahagirdar D, Pal JK, Sharma NK
Abstract
The microenvironment in which cancer resides plays an important role in regulating cancer survival, progression, malignancy and drug resistance. Tumor microenvironment (TME) consists of heterogeneous number and types of cellular and non-cellular components that vary in relation to tumor phenotype and genotype. In recent, non-cellular secreted components of microenvironmental heterogeneity have been suggested to contain various growth factors, cytokines, RNA, DNA, metabolites, structural matrix and matricellular proteins. These non-cellular components have been indicated to orchestrate numerous ways to support cancer survival and progression by providing metabolites, energy, growth signals, evading immune surveillance, drug resistance environment, metastatic and angiogenesis cues. Thus, switching action from pro-cancer to anti-cancer activities of these secreted components of TME has been considered as a new avenue in cancer therapeutics and drug resistance. In this report, we summarize the recent pre-clinical and clinical evidences to emphasize the importance of non-cellular components of TME in achieving precision therapeutics and biomarker study.
PMID: 29219656 [PubMed - as supplied by publisher]
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Social cognition and aggression in methamphetamine dependence with and without a history of psychosis
Abstract
In substance use and psychotic disorders, socially problematic behaviours, such as high aggression may, in part, be explained by deficits in social cognition skills, like the detection of emotions or intentions in others. The aim of this study was to assess the magnitude of social cognition impairment and its association with aggression in individuals with methamphetamine (MA) dependence, methamphetamine-associated psychosis (MAP), and healthy controls (CTRL). A total of 20 MAP participants, 21 MA-dependent participants without psychosis, and 21 CTRL participants performed a facial morphing emotion recognition task (ERT) across four basic emotions (anger, fear, happiness and sadness) and the reading the mind in the eyes task (RMET), and completed the aggression questionnaire. Both MA-dependent groups showed impairment in social cognition in terms of lower RMET scores relative to CTRL participants (MA; p = .047; MAP: p < .001). Additionally, performance decrements were significantly greater in MAP (p = .040), compared to MA-dependent participants. While deficits in recognising emotional expressions were restricted to anger in the MA group (p = .020), a generalized impairment across all four emotions was observed in MAP (all p ≤ .001). Additionally, both patient groups demonstrated higher levels of aggression than CTRLs, yet no association was found with social cognition. This study supported the notion of deficits in recognising facial emotional expressions and inferring mental states of others in MA dependence, with additional impairments in MAP. Failure to detect an association between social cognitive impairment and aggressive behaviour may implicate independent disturbances of the two phenomena in MA dependence.
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Identifying and monitoring neurons that undergo metamorphosis-regulated cell death (metamorphoptosis) by a neuron-specific caspase sensor (Casor) in Drosophila melanogaster
Abstract
Activation of caspases is an essential step toward initiating apoptotic cell death. During metamorphosis of Drosophila melanogaster, many larval neurons are programmed for elimination to establish an adult central nervous system (CNS) as well as peripheral nervous system (PNS). However, their neuronal functions have remained mostly unknown due to the lack of proper tools to identify them. To obtain detailed information about the neurochemical phenotypes of the doomed larval neurons and their timing of death, we generated a new GFP-based caspase sensor (Casor) that is designed to change its subcellular position from the cell membrane to the nucleus following proteolytic cleavage by active caspases. Ectopic expression of Casor in vCrz and bursicon, two different peptidergic neuronal groups that had been well-characterized for their metamorphic programmed cell death, showed clear nuclear translocation of Casor in a caspase-dependent manner before their death. We found similar events in some cholinergic neurons from both CNS and PNS. Moreover, Casor also reported significant caspase activities in the ventral and dorsal common excitatory larval motoneurons shortly after puparium formation. These motoneurons were previously unknown for their apoptotic fate. Unlike the events seen in the neurons, expression of Casor in non-neuronal cell types, such as glial cells and S2 cells, resulted in the formation of cytoplasmic aggregates, preventing its use as a caspase sensor in these cell types. Nonetheless, our results support Casor as a valuable molecular tool not only for identifying novel groups of neurons that become caspase-active during metamorphosis but also for monitoring developmental timing and cytological changes within the dying neurons.
http://ift.tt/2B4R7zR
Social cognition and aggression in methamphetamine dependence with and without a history of psychosis
Abstract
In substance use and psychotic disorders, socially problematic behaviours, such as high aggression may, in part, be explained by deficits in social cognition skills, like the detection of emotions or intentions in others. The aim of this study was to assess the magnitude of social cognition impairment and its association with aggression in individuals with methamphetamine (MA) dependence, methamphetamine-associated psychosis (MAP), and healthy controls (CTRL). A total of 20 MAP participants, 21 MA-dependent participants without psychosis, and 21 CTRL participants performed a facial morphing emotion recognition task (ERT) across four basic emotions (anger, fear, happiness and sadness) and the reading the mind in the eyes task (RMET), and completed the aggression questionnaire. Both MA-dependent groups showed impairment in social cognition in terms of lower RMET scores relative to CTRL participants (MA; p = .047; MAP: p < .001). Additionally, performance decrements were significantly greater in MAP (p = .040), compared to MA-dependent participants. While deficits in recognising emotional expressions were restricted to anger in the MA group (p = .020), a generalized impairment across all four emotions was observed in MAP (all p ≤ .001). Additionally, both patient groups demonstrated higher levels of aggression than CTRLs, yet no association was found with social cognition. This study supported the notion of deficits in recognising facial emotional expressions and inferring mental states of others in MA dependence, with additional impairments in MAP. Failure to detect an association between social cognitive impairment and aggressive behaviour may implicate independent disturbances of the two phenomena in MA dependence.
http://ift.tt/2BZagAW
FTO Gene Affects Obesity and Breast Cancer Through Similar Mechanisms: A New Insight into the Molecular Therapeutic Targets.
FTO Gene Affects Obesity and Breast Cancer Through Similar Mechanisms: A New Insight into the Molecular Therapeutic Targets.
Nutr Cancer. 2017 Dec 08;:1-7
Authors: Akbari ME, Gholamalizadeh M, Doaei S, Mirsafa F
Abstract
OBJECTIVES: This review focused on the possible mediatory role of the FTO in the association between obesity and breast cancer.
METHOD: All articles published in English from June 1990 to January 2017 were studied. The search terms used were FTO gene, FTO polymorphism, breast cancer, and obesity. Inclusion criteria consisted of assessment of the relationship between FTO polymorphisms and/or FTO expression level with obesity and/or breast cancer as a primary outcome.
RESULTS: The FTO gene may have a role in the cellular sensing of macronutrients. Over expression of the FTO gene increases the levels of mammalian target of rapamycin (mTOR) signaling that is a key regulator of cell growth. Moreover, some SNPs in intron locations of the FTO gene exert their effects on body mass index, body composition and breast cancer risk through change of the homeobox transcription factor iriquois 3 (IRX3) gene expression level.
CONCLUSION: The FTO gene may has a critical role in obesity and breast cancer. Similar molecular mechanisms may play a role in the development of breast cancer and obesity. If this result is correct then, it will be interesting to examine the FTO gene as a molecular therapeutics target.
PMID: 29220587 [PubMed - as supplied by publisher]
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Elevated Serum Vitamin B12 Levels as a Prognostic Factor for Survival Time in Metastatic Cancer Patients: A Retrospective Study.
Elevated Serum Vitamin B12 Levels as a Prognostic Factor for Survival Time in Metastatic Cancer Patients: A Retrospective Study.
Nutr Cancer. 2017 Dec 08;:1-8
Authors: Oh HK, Lee JY, Eo WK, Yoon SW, Han SN
Abstract
BACKGROUND: Serum vitamin B12 levels have been proposed as one of the survival prediction factors, although no survival analysis in metastatic cancer patients has been conducted yet. This study examined whether serum vitamin B12 levels could be a prognostic factor in metastatic cancer patients.
METHODS: Data from a retrospective chart review were used to perform Kaplan-Meier and multivariate analyses of the Cox proportional hazards. Subgroup analysis was performed on patients without a liver lesion (hepatocellular carcinoma or liver metastasis).
RESULTS: A total of 523 patients were included. The median survival time was 1.8 months (mo) in the high B12 group (>911 pg/mL) and 5.1 mo in the normal B12 group (211-911 pg/mL) (p < 0.001). In patients without a liver lesion, the median survival times were 2.1 and 6.1 mo in the high and normal B12 groups, respectively (p < 0.001). Multivariate analysis revealed that serum vitamin B12 level was an independent prognostic factor for overall survival (hazard ratio [HR]: 1.62; 95% confidence interval [CI]: 1.34-1.96, p < 0.001).
CONCLUSION: Serum vitamin B12 level can be used to predict survival time in metastatic cancer patients. Further large-scale cohort studies are required to confirm these findings.
PMID: 29220583 [PubMed - as supplied by publisher]
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American Journal of Cancer Research; +19 new citations
19 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
American Journal of Cancer Research
These pubmed results were generated on 2017/12/09
PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
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FTO Gene Affects Obesity and Breast Cancer Through Similar Mechanisms: A New Insight into the Molecular Therapeutic Targets.
FTO Gene Affects Obesity and Breast Cancer Through Similar Mechanisms: A New Insight into the Molecular Therapeutic Targets.
Nutr Cancer. 2017 Dec 08;:1-7
Authors: Akbari ME, Gholamalizadeh M, Doaei S, Mirsafa F
Abstract
OBJECTIVES: This review focused on the possible mediatory role of the FTO in the association between obesity and breast cancer.
METHOD: All articles published in English from June 1990 to January 2017 were studied. The search terms used were FTO gene, FTO polymorphism, breast cancer, and obesity. Inclusion criteria consisted of assessment of the relationship between FTO polymorphisms and/or FTO expression level with obesity and/or breast cancer as a primary outcome.
RESULTS: The FTO gene may have a role in the cellular sensing of macronutrients. Over expression of the FTO gene increases the levels of mammalian target of rapamycin (mTOR) signaling that is a key regulator of cell growth. Moreover, some SNPs in intron locations of the FTO gene exert their effects on body mass index, body composition and breast cancer risk through change of the homeobox transcription factor iriquois 3 (IRX3) gene expression level.
CONCLUSION: The FTO gene may has a critical role in obesity and breast cancer. Similar molecular mechanisms may play a role in the development of breast cancer and obesity. If this result is correct then, it will be interesting to examine the FTO gene as a molecular therapeutics target.
PMID: 29220587 [PubMed - as supplied by publisher]
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Elevated Serum Vitamin B12 Levels as a Prognostic Factor for Survival Time in Metastatic Cancer Patients: A Retrospective Study.
Elevated Serum Vitamin B12 Levels as a Prognostic Factor for Survival Time in Metastatic Cancer Patients: A Retrospective Study.
Nutr Cancer. 2017 Dec 08;:1-8
Authors: Oh HK, Lee JY, Eo WK, Yoon SW, Han SN
Abstract
BACKGROUND: Serum vitamin B12 levels have been proposed as one of the survival prediction factors, although no survival analysis in metastatic cancer patients has been conducted yet. This study examined whether serum vitamin B12 levels could be a prognostic factor in metastatic cancer patients.
METHODS: Data from a retrospective chart review were used to perform Kaplan-Meier and multivariate analyses of the Cox proportional hazards. Subgroup analysis was performed on patients without a liver lesion (hepatocellular carcinoma or liver metastasis).
RESULTS: A total of 523 patients were included. The median survival time was 1.8 months (mo) in the high B12 group (>911 pg/mL) and 5.1 mo in the normal B12 group (211-911 pg/mL) (p < 0.001). In patients without a liver lesion, the median survival times were 2.1 and 6.1 mo in the high and normal B12 groups, respectively (p < 0.001). Multivariate analysis revealed that serum vitamin B12 level was an independent prognostic factor for overall survival (hazard ratio [HR]: 1.62; 95% confidence interval [CI]: 1.34-1.96, p < 0.001).
CONCLUSION: Serum vitamin B12 level can be used to predict survival time in metastatic cancer patients. Further large-scale cohort studies are required to confirm these findings.
PMID: 29220583 [PubMed - as supplied by publisher]
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Magnetic resonance imaging of cardiovascular thrombi in children
Abstract
Cardiovascular thrombosis is rare in children and usually occurs in the presence of predisposing conditions, such as indwelling vascular catheters, tumors, aneurysms, ventricular dysfunction, or after surgery. Clots can occur in the cardiac chambers, arteries or veins, or inside conduits. Detection of thrombi is feasible with a variety of magnetic resonance imaging (MRI) techniques, including unenhanced methods but also contrast-enhanced MR angiography. In this essay we illustrate the MRI appearance of cardiovascular thrombosis in children and suggest an imaging protocol based on our clinical experience.
http://ift.tt/2BoDLin
Magnetic resonance imaging of cardiovascular thrombi in children
Abstract
Cardiovascular thrombosis is rare in children and usually occurs in the presence of predisposing conditions, such as indwelling vascular catheters, tumors, aneurysms, ventricular dysfunction, or after surgery. Clots can occur in the cardiac chambers, arteries or veins, or inside conduits. Detection of thrombi is feasible with a variety of magnetic resonance imaging (MRI) techniques, including unenhanced methods but also contrast-enhanced MR angiography. In this essay we illustrate the MRI appearance of cardiovascular thrombosis in children and suggest an imaging protocol based on our clinical experience.
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Expanding the use of abiraterone in prostate cancer: Is earlier always better?
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Multispectral imaging reveals hyper active TGF-β signaling in colorectal cancer
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The levels of mutant K-RAS and mutant N-RAS are rapidly reduced in a Beclin1 / ATG5 -dependent fashion by the irreversible ERBB1/2/4 inhibitor neratinib
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Modulating secreted components of tumor microenvironment: A masterstroke in tumor therapeutics
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Expanding the use of abiraterone in prostate cancer: Is earlier always better?
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Multispectral imaging reveals hyper active TGF-β signaling in colorectal cancer
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http://ift.tt/2iKNQLg
Image-guided adaptive radiotherapy improves acute toxicity during intensity-modulated radiation therapy for head and neck cancer
Abstract
Purpose
The purpose of this study was to evaluate the impact of an image-guided adaptive re-planning strategy on patients treated by intensity-modulated radiotherapy (IMRT) for head and neck cancer.
Methods and materials
Among 198 patients with head and neck cancer comprising the primary study population, 79 (40%) underwent adaptive radiotherapy with modification of the original IMRT midway during treatment.
Results
The incidence of grade 3+ acute skin toxicity was 15 and 35% among patients treated with and without adaptive radiotherapy, respectively (p = 0.01). The incidence of grade 3+ oral mucositis was 15 and 29%, respectively (p = 0.03). There was no significant difference in the 2-year rates of local-regional control or overall survival between the two cohorts (p > 0.05, for both).
Conclusion
The use of an image-guided adaptive radiotherapy strategy reduced the incidence of high-grade skin toxicity and oral mucositis in the acute setting. Further studies are needed to better define which subset of patients may benefit the most.
http://ift.tt/2nGzSza
Anemia and Iron Status Among Different Body Size Phenotypes in Chinese Adult Population: a Nation-Wide, Health and Nutrition Survey
Abstract
Previous studies have shown that there is a controversial relationship between iron homeostasis and obesity. This study aims to explore the relationship of anemia and iron status with different body size phenotypes in adult Chinese population. Using information on iron status-related parameters and lifestyle data from 8462 participants of the 2009 wave of China Health and Nutrition Survey (2009 CHNS), we performed multivariable logistic regression analyses to estimate the odds ratios (ORs) for the risk of anemia and iron parameters according to different body size phenotypes. Participants with higher body mass index (BMI) had a lower anemia prevalence with significant trends in both metabolic status groups (P < 0.001). Serum ferritin, transferrin, and soluble transferrin receptor (sTfR)/log ferritin index were significant in different metabolic status groups and in different body size phenotypes, respectively. The ORs for higher ferritin and transferrin increased across different body size phenotypes in both genders, and for sTfR/log ferritin index decreased (P < 0.01 for trend). This association was still statistically significant after adjustment for multiple confounders. We found an inverse association of BMI levels with the prevalence of anemia and strong association of serum ferritin and transferrin with higher risk of obesity or overweight in both metabolic status groups.
http://ift.tt/2BmYPFR
Anemia and Iron Status Among Different Body Size Phenotypes in Chinese Adult Population: a Nation-Wide, Health and Nutrition Survey
Abstract
Previous studies have shown that there is a controversial relationship between iron homeostasis and obesity. This study aims to explore the relationship of anemia and iron status with different body size phenotypes in adult Chinese population. Using information on iron status-related parameters and lifestyle data from 8462 participants of the 2009 wave of China Health and Nutrition Survey (2009 CHNS), we performed multivariable logistic regression analyses to estimate the odds ratios (ORs) for the risk of anemia and iron parameters according to different body size phenotypes. Participants with higher body mass index (BMI) had a lower anemia prevalence with significant trends in both metabolic status groups (P < 0.001). Serum ferritin, transferrin, and soluble transferrin receptor (sTfR)/log ferritin index were significant in different metabolic status groups and in different body size phenotypes, respectively. The ORs for higher ferritin and transferrin increased across different body size phenotypes in both genders, and for sTfR/log ferritin index decreased (P < 0.01 for trend). This association was still statistically significant after adjustment for multiple confounders. We found an inverse association of BMI levels with the prevalence of anemia and strong association of serum ferritin and transferrin with higher risk of obesity or overweight in both metabolic status groups.
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LAG-3: another brake to release in breast cancer?
Upregulation of inhibitory immune checkpoints is critical for the control of T-cell activation in order to prevent autoimmunity and tissue damage. It is now clear that tumors can hijack immune checkpoint mechanisms as protection against the anticancer T-cell response. Blockade of the PD-1/PD-L1 immune checkpoint pathway has created a revolution in the treatment of melanoma, lung cancer and several other cancer types. In metastatic breast cancer patients, the response rates to PD-1 blocking antibodies are modest (4%–25%), but durable responses are seen [1–7]. Given that the majority of patients do not have clinical benefit, there is an urgent need to improve immunotherapy for breast cancer patients. This optimization is not a paved road and requires the integration of different parallel approaches, such as the search for predictive biomarkers [8], combination treatment with conventional therapies [9, 10], strategies to convert cold tumors into hot tumors [4, 11] and development of novel immunomodulatory compounds.
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Incremental improvement in osteosarcoma chemotherapy?
Osteosarcoma is one of the first solid cancers for which a survival benefit from adjuvant chemotherapy was established [1, 2]. After decades of clinical research to improve on results obtained in the 1980s, the long-standing chemotherapy regimen of doxorubicin and cisplatin with or without methotrexate remains a standard treatment of osteosarcoma, resulting in a 5-year survival rate of more than 60% in patients with localized disease [3, 4]. In patients with metastatic osteosarcoma at diagnosis, or with distant disease relapse after treatment of localized disease, the long-term survival rate is <20%, and new therapies are much needed for this group of patients [5]. Neither the intensification of chemotherapy by adding ifosfamide and etoposide nor the use of muramyl tripeptide or traztuzumab has improved the survival of patients with metastatic osteosarcoma [6–8]. However, cure can be achieved in patients with metastatic osteosarcoma who undergo metastasectomy [5, 9].
http://ift.tt/2Ap9Jek
http://ift.tt/2Ap9Jek
Understanding personal risk of oropharyngeal cancer: risk-groups for oncogenic oral HPV infection and oropharyngeal cancer
Abstract
Background
Incidence of human papillomavirus (HPV)-related oropharyngeal cancer is increasing. There is interest in identifying healthy individuals most at risk for development of oropharyngeal cancer to inform screening strategies. Patients and methods
All data are from 2009 to 2014, including 13 089 people ages 20–69 in the National Health and Nutrition Examination Survey (NHANES), oropharyngeal cancer cases from the Surveillance, Epidemiology, and End Results (SEER 18) registries (representing ∼28% of the US population), and oropharyngeal cancer mortality from National Center for Health Statistics (NCHS). Primary study outcomes are (i) prevalence of oncogenic HPV DNA in an oral rinse and gargle sample, and (ii) incident oropharyngeal squamous cell cancer. Results
Oncogenic oral HPV DNA is detected in 3.5% of all adults age 20–69 years; however, the lifetime risk of oropharyngeal cancer is low (37 per 10 000). Among men 50–59 years old, 8.1% have an oncogenic oral HPV infection, 2.1% have an oral HPV16 infection, yet only 0.7% will 'ever' develop oropharyngeal cancer in their lifetime. Oncogenic oral HPV prevalence was higher in men than women, and increased with number of lifetime oral sexual partners and tobacco use. Men who currently smoked and had ≥5 lifetime oral sexual partners had 'elevated risk' (prevalence = 14.9%). Men with only one of these risk factors (i.e. either smoked and had 2–4 partners or did not smoke and had ≥5 partners) had 'medium risk' (7.3%). Regardless of what other risk factors participants had, oncogenic oral HPV prevalence was 'low' among those with only ≤1 lifetime oral sexual partner (women = 0.7% and men = 1.7%). Conclusions
Screening based upon oncogenic oral HPV detection would be challenging. Most groups have low oncogenic oral HPV prevalence. In addition to the large numbers of individuals who would need to be screened to identify prevalent oncogenic oral HPV, the lifetime risk of developing oropharyngeal caner among those with infection remains low.http://ift.tt/2BkxhkF
Emerging treatment paradigms for brain metastasis in non-small-cell lung cancer: an overview of the current landscape and challenges ahead
Abstract
Advances in the last decade in genomic profiling and the identification of druggable targets amenable to biological agents have transformed the management and survival of a subgroup of patients with brain metastasis in non-small-cell lung cancer. In parallel, clinicians have reevaluated the role of whole brain radiotherapy in selected patients with brain metastases to reduce neurocognitive toxicity. Continual progress in this understudied field is required: optimization of the sequence of schedules for therapies in patients with brain metastases of differing genomic profiles, focusing on new strategies to overcome mechanisms of biological resistance and increasing drug penetrability into the central nervous system. This review summarizes the field to date and possible treatment strategies based on current evidence.http://ift.tt/2Ap9G28
Refractory or relapsed aggressive B-cell lymphoma failing (R)-CHOP: an analysis of patients treated on the RICOVER-60 trial
Abstract
Background
The prognosis of elderly patients with aggressive B-non-Hodgkin's lymphoma after first lymphoma-related treatment failure (TF-L) is not well described. Methods
We analysed patient characteristics including the presence of MYC rearrangements and MYC-expression immunohistochemistry (IHC) at diagnosis and modalities of salvage therapy and their impact on the prognosis of patients between 61 and 80 years who had been treated on the RICOVER-60 trial. Results
TF-L occurred in 301 of the 1222 (24.6%) patients; 297 patients could be analysed. Prognosis was extremely poor in patients with primary progressive disease or early relapse (≤12 months) with median survivals of 3.3 and 6.4 months. Survival after TF-L was significantly lower in patients pretreated with R-CHOP compared with CHOP (23.0% versus 36.4% at 2 years, P = 0.016). In patients with MYC translocation at diagnosis Rituximab reduced the risk of TF-L from 58.8% to 26.3%. Survival after TF-L was significant longer for patients after CHOP without MYC translocations (31.8% versus 0% at 2 years, P < 0.001) or negative MYC-IHC (41.0% versus 16.8% at 2 years, P = 0.017) but not after R-CHOP. 224 patients (75.4%) received salvage therapy. Rituximab was part of salvage therapy in 57.4% and improved 2-year survival rate from 20.7% to 46.8% (P < 0.001). The benefit of R was significant after first-line CHOP [2-year overall survival (OS) 49.6% versus 19.1%, P < 0.001] as well as after R-CHOP (2-year OS 33.1% and 22.5%, P = 0.034). For patients pretreated with R-CHOP long-term survival was below 15% regardless of the treatment chosen. Conclusion
MYC rearrangement and IHC are adverse prognostic factors after TF-L for CHOP treated patients, rituximab as part of first-line therapy reduced the effects of MYC-break. Rituximab improves results of any type of salvage therapy; however, survival after progression/relapse of aggressive B-cell lymphoma in elderly patients pretreated with (R)-CHOP is poor regardless of treatment chosen.http://ift.tt/2nJKrSm
DPYD genotype-guided fluoropyrimidines dose: is it ready for prime time?
For over 50 years, fluoropyrimidines have been the cornerstone of anticancer drugs for various types of solid cancers. Treatment with these drugs—5-fluorouracil (FU) and its oral prodrugs, capecitabine and tegafur—is generally well-tolerated, except in a small proportion of patients who develop severe and life-threatening early toxicity. This toxicity is mainly associated with a deficiency of the primary fluoropyrimidine detoxifying enzyme, dihydropryrimidine dehydrogenase (DPD) [1]. The drug labels of FU and capecitabine state DPD deficiency as a contraindication, but they give no warning for the 3%–8% of the population who are partially DPD deficient.
http://ift.tt/2Aoz3Bk
http://ift.tt/2Aoz3Bk
SELECT-2: a phase II, double-blind, randomized, placebo-controlled study to assess the efficacy of selumetinib plus docetaxel as a second-line treatment of patients with advanced or metastatic non-small-cell lung cancer
Abstract
Background
Combination of selumetinib plus docetaxel provided clinical benefit in a previous phase II trial for patients with KRAS-mutant advanced non-small-cell lung cancer (NSCLC). The phase II SELECT-2 trial investigated safety and efficacy of selumetinib plus docetaxel for patients with advanced or metastatic NSCLC. Patients and methods
Patients who had disease progression after first-line anti-cancer therapy were randomized (2 : 2 : 1) to selumetinib 75 mg b.i.d. plus docetaxel 60 or 75 mg/m2 (SEL + DOC 60; SEL + DOC 75), or placebo plus docetaxel 75 mg/m2 (PBO + DOC 75). Patients were initially enrolled independently of KRAS mutation status, but the protocol was amended to include only patients with centrally confirmed KRAS wild-type NSCLC. Primary end point was progression-free survival (PFS; RECIST 1.1); statistical analyses compared each selumetinib group with PBO + DOC 75 for KRAS wild-type and overall (KRAS mutant or wild-type) populations. Results
A total of 212 patients were randomized; 69% were KRAS wild-type. There were no statistically significant improvements in PFS or overall survival for overall or KRAS wild-type populations in either selumetinib group compared with PBO + DOC 75. Overall population median PFS for SEL + DOC 60, SEL + DOC 75 compared with PBO + DOC 75 was 3.0, 4.2, and 4.3 months, HRs: 1.12 (90% CI: 0.8, 1.61) and 0.92 (90% CI: 0.65, 1.31), respectively. In the overall population, a higher objective response rate (ORR; investigator assessed) was observed for SEL + DOC 75 (33%) compared with PBO + DOC 75 (14%); odds ratio: 3.26 (90% CI: 1.47, 7.95). Overall the tolerability profile of SEL + DOC was consistent with historical data, without new or unexpected safety concerns identified. Conclusion
The primary end point (PFS) was not met. The higher ORR with SEL + DOC 75 did not translate into prolonged PFS for the overall or KRAS wild-type patient populations. No clinical benefit was observed with SEL + DOC in KRAS wild-type patients compared with docetaxel alone. No unexpected safety concerns were reported. Trial identifier
Clinicaltrials.gov NCT01750281.http://ift.tt/2nIkKBv
Gougerot-Sjogren-like syndrome under PD-1 inhibitor treatment
A 36-year-old female patient with no significant medical history except hypothyroidism was diagnosed with left parotid acinic cell carcinoma that was treated by radical parotidectomy followed by adjuvant radiotherapy (50 Gy) in 2004. Seven years after the initial diagnosis, the patient developed histologically confirmed metastases on the left adrenal gland and the lung, for which systemic therapy was indicated. The patient participated in two successive studies and received lapatinib and then an EZH-2 inhibitor. In March 2016, the patient's adrenal lesion progressed, and she started treatment with pembrolizumab, 200 mg, every 3 weeks. At the time of the 11th injection, the patient experienced a retinal detachment that was linked to her myopia. The detachment was treated by surgery and amoxicillin for 7 days. Subsequently, the patient developed an oral candidiasis that was treated with systemic fungizone. At the time of the 13th injection, in December 2016, the patient experienced a debilitating grade 2 dry-eye syndrome that was associated with grade 1 conjunctival hyperemia, grade 2 xerostomia, and grade 1 skin rash on both hands. Therefore, serum protein electrophoresis (SPEP) and determination of antinuclear antibodies (ANA) [particularly Sjogren's syndrome A/Sjogren's syndrome B (SSA/SSB)] were carried out. A salivary gland biopsy could not be conducted because of the patient's radiation history. The SPEP and the ANA were normal. Concomitantly, the CT-scan showed a stable disease using the RECIST criteria v1.1.
http://ift.tt/2BmZRlv
http://ift.tt/2BmZRlv
Molecular Tumor Boards: current practice and future needs
Abstract
Background
Due to rapid technical advances, steeply declining sequencing costs, and the ever-increasing number of targeted therapies, it can be expected that extensive tumor sequencing such as whole-exome and whole-genome sequencing will soon be applied in standard care. Clinicians will thus be confronted with increasingly complex genetic information and multiple test-platforms to choose from. General medical training, meanwhile, can hardly keep up with the pace of innovation. Consequently, there is a rapidly growing gap between clinical knowledge and genetic potential in cancer care. Multidisciplinary Molecular Tumor Boards (MTBs) have been suggested as a means to address this disparity, but shared experiences are scarce in literature and no quality requirements or guidelines have been published to date. Methods
Based on literature review, a survey among hospitals in The Netherlands, and our own experience with the establishment of a nationally operating MTB, this article evaluates current knowledge and unmet needs and lays out a strategy for successful MTB implementation. Results
Having access to an MTB can improve and increase the application of genetics-guided cancer care. In our survey, however, <50% of hospitals and only 5% of nonacademic hospitals had access to an MTB. In addition, current MTBs vary widely in terms of composition, tasks, tools, and workflow. This may not only lead to variation in quality of care but also hinders data sharing and thus creation of an effective learning community. Conclusions
This article acknowledges a leading role for MTBs to govern (extensive) tumor sequencing into daily practice and proposes three basic necessities for successful MTB implementation: (i) global harmonization in cancer sequencing practices and procedures, (ii) minimal member and operational requirements, and (iii) an appropriate unsolicited findings policy. Meeting these prerequisites would not only optimize MTB functioning but also improve general interpretation and application of genomics-guided cancer care.http://ift.tt/2ALWWS4
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