To test the hypothesis that atlas-based active bone marrow (ABM)-sparing intensity modulated radiation therapy (IMRT) yields similar dosimetric results compared to custom ABM-sparing IMRT for cervical cancer patients.
http://ift.tt/2pWbK8D
Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Τετάρτη 17 Μαΐου 2017
Feasibility of atlas-based active bone marrow sparing intensity modulated radiation therapy for cervical cancer
Pediatric nasal surgery prior to puberty is not only safe, but may prevent facial deformity in certain patients.
Pediatric nasal surgery: timing and technique.
από Gary, Celeste C. στο Current Opinion in Otolaryngology & Head and Neck Surgery - Published Ahead-of-Print
Μετάφραση άρθρου
Purpose of review: Timing of pediatric nasal surgery has always been a controversial topic. Concern over disrupting growing parts of the face and causing permanent facial deformity has led to a primarily conservative approach. Many surgeons feel that it is prudent to wait until the patient has completed nasal growth after puberty to pursue nasal surgery. Recent findings: Recently, this attitude has been challenged with evidence that not only is nasal surgery in the pediatric age group not a detriment to facial growth, but failure to correct significant nasal deformity may actually cause dysmorphic facial growth secondary to obligate mouth breathing. Because of this, recent studies have focused on determining safe surgical techniques for pediatric nasal surgery, including inferior turbinate reduction, septoplasty and rhinoplasty. Research focus on this topic has also been expanded to include quality-of-life measures after nasal surgery. Summary: Pediatric nasal surgery prior to puberty is not only safe, but may prevent facial deformity in certain patients. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480
Long noncoding RNAs: emerging regulators of tumor angiogenesis
Future Oncology Ahead of Print.
http://ift.tt/2quN3mL
Long noncoding RNAs: emerging regulators of tumor angiogenesis
Future Oncology Ahead of Print.
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Long noncoding RNAs: emerging regulators of tumor angiogenesis
Future Oncology Ahead of Print.
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Pyruvate kinase inhibits proliferation during postnatal cerebellar neurogenesis and suppresses medulloblastoma formation
Aerobic glycolysis supports proliferation through unresolved mechanisms. We have previously shown that aerobic glycolysis is required for the regulated proliferation of cerebellar granule neuron progenitors (CGNPs), and for the growth of CGNP-derived medulloblastoma. Blocking the initiation of glycolysis via deletion of Hexokinase-2 (Hk2) disrupts CGNP proliferation and restricts medulloblastoma growth. Here, we assessed whether disrupting Pyruvate kinase-M (Pkm), an enzyme that acts in the terminal steps of glycolysis, would alter CGNP metabolism, proliferation and tumorigenesis. We observed a dichotomous pattern of PKM expression, in which post-mitotic neurons throughout the brain expressed the constitutively active PKM1 isoform, while neural progenitors and medulloblastomas exclusively expressed the less active PKM2. Isoform-specific Pkm2 deletion in CGNPs blocked all Pkm expression. Pkm2-deleted CGNPs showed reduced lactate production and increased SHH-driven proliferation. 13C-flux analysis showed that Pkm2 deletion reduced the flow of glucose carbons into lactate and glutamate without markedly increasing glucose-to-ribose flux. Pkm2 deletion accelerated tumor formation in medulloblastoma-prone ND2:SmoA1 mice, indicating the disrupting PKM releases CGNPs from a tumor-suppressive effect. These findings show that distal and proximal disruptions of glycolysis have opposite effects on proliferation, and that efforts to block the oncogenic effect of aerobic glycolysis must target reactions upstream of PKM.
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NEMO, a transcriptional target of estrogen and progesterone, is linked to tumor suppressor PML in breast cancer
The beneficial versus detrimental roles of estrogen plus progesterone (E+P) in breast cancer remains controversial. Here we report a beneficial mechanism of E+P treatment in breast cancer cells driven by transcriptional upregulation of the NFκB modulator NEMO, which in turn promotes expression of the tumor suppressor protein PML. E+P treatment of patient-derived epithelial cells derived from ductal carcinoma in situ (DCIS) increased secretion of the pro-inflammatory cytokine IL-6. Mechanistic investigations indicated that IL-6 upregulation occurred as a result of transcriptional upregulation of NEMO, the gene for which harbored estrogen receptor (ER) binding sites within its promoter. Accordingly, E+P treatment of breast cancer cells increased ER binding to the NEMO promoter, thereby increasing NEMO expression, NFκB activation and IL-6 secretion. In two mouse xenograft models of DCIS, we found that RNAi-mediated silencing of NEMO increased tumor invasion and progression. This seemingly paradoxical result was linked to NEMO-mediated regulation of NFκB and IL-6 secretion, increased phosphorylation of STAT3 on Ser727 and increased expression of PML, a STAT3 transcriptional target. In identifying NEMO as a pivotal transcriptional target of E+P signaling in breast cancer cells, our work offers a mechanistic explanation for the paradoxical anti-tumorigenic roles of E+P in breast cancer by showing how it upregulates the tumor suppressor protein PML.
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Increased T cell infiltration elicited by Erk5 deletion in a Pten-deficient mouse model of prostate carcinogenesis.
Prostate cancer (PCa) does not appear to respond to immune checkpoint therapies where T cell infiltration may be a key limiting factor. Here we report evidence that ablating the growth regulatory kinase Erk5 can increase T cell infiltration in an established Pten-deficient mouse model of human PCa. Mice that were doubly mutant in prostate tissue for Pten and Erk5 (prostate DKO) exhibited a markedly increased median survival with reduced tumor size and proliferation compared to control Pten-mutant mice, the latter of which exhibited increased Erk5 mRNA expression. A comparative transcriptomic analysis revealed upregulation in prostate DKO mice of the chemokines Ccl5 and Cxcl10, two potent chemoattractants for T lymphocytes. Consistent with this effect, we observed a relative increase in a predominantly CD4+ T cell infiltrate in the prostate epithelial and stroma of tumors from DKO mice. Collectively, our results offer a preclinical proof of concept for ERK5 as a target to enhance T cell infiltrates in prostate cancer, with possible implications for leveraging immune therapy in this disease.
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Pyruvate kinase inhibits proliferation during postnatal cerebellar neurogenesis and suppresses medulloblastoma formation
Aerobic glycolysis supports proliferation through unresolved mechanisms. We have previously shown that aerobic glycolysis is required for the regulated proliferation of cerebellar granule neuron progenitors (CGNPs), and for the growth of CGNP-derived medulloblastoma. Blocking the initiation of glycolysis via deletion of Hexokinase-2 (Hk2) disrupts CGNP proliferation and restricts medulloblastoma growth. Here, we assessed whether disrupting Pyruvate kinase-M (Pkm), an enzyme that acts in the terminal steps of glycolysis, would alter CGNP metabolism, proliferation and tumorigenesis. We observed a dichotomous pattern of PKM expression, in which post-mitotic neurons throughout the brain expressed the constitutively active PKM1 isoform, while neural progenitors and medulloblastomas exclusively expressed the less active PKM2. Isoform-specific Pkm2 deletion in CGNPs blocked all Pkm expression. Pkm2-deleted CGNPs showed reduced lactate production and increased SHH-driven proliferation. 13C-flux analysis showed that Pkm2 deletion reduced the flow of glucose carbons into lactate and glutamate without markedly increasing glucose-to-ribose flux. Pkm2 deletion accelerated tumor formation in medulloblastoma-prone ND2:SmoA1 mice, indicating the disrupting PKM releases CGNPs from a tumor-suppressive effect. These findings show that distal and proximal disruptions of glycolysis have opposite effects on proliferation, and that efforts to block the oncogenic effect of aerobic glycolysis must target reactions upstream of PKM.
http://ift.tt/2rsNtbh
NEMO, a transcriptional target of estrogen and progesterone, is linked to tumor suppressor PML in breast cancer
The beneficial versus detrimental roles of estrogen plus progesterone (E+P) in breast cancer remains controversial. Here we report a beneficial mechanism of E+P treatment in breast cancer cells driven by transcriptional upregulation of the NFκB modulator NEMO, which in turn promotes expression of the tumor suppressor protein PML. E+P treatment of patient-derived epithelial cells derived from ductal carcinoma in situ (DCIS) increased secretion of the pro-inflammatory cytokine IL-6. Mechanistic investigations indicated that IL-6 upregulation occurred as a result of transcriptional upregulation of NEMO, the gene for which harbored estrogen receptor (ER) binding sites within its promoter. Accordingly, E+P treatment of breast cancer cells increased ER binding to the NEMO promoter, thereby increasing NEMO expression, NFκB activation and IL-6 secretion. In two mouse xenograft models of DCIS, we found that RNAi-mediated silencing of NEMO increased tumor invasion and progression. This seemingly paradoxical result was linked to NEMO-mediated regulation of NFκB and IL-6 secretion, increased phosphorylation of STAT3 on Ser727 and increased expression of PML, a STAT3 transcriptional target. In identifying NEMO as a pivotal transcriptional target of E+P signaling in breast cancer cells, our work offers a mechanistic explanation for the paradoxical anti-tumorigenic roles of E+P in breast cancer by showing how it upregulates the tumor suppressor protein PML.
http://ift.tt/2qTMV1e
Increased T cell infiltration elicited by Erk5 deletion in a Pten-deficient mouse model of prostate carcinogenesis.
Prostate cancer (PCa) does not appear to respond to immune checkpoint therapies where T cell infiltration may be a key limiting factor. Here we report evidence that ablating the growth regulatory kinase Erk5 can increase T cell infiltration in an established Pten-deficient mouse model of human PCa. Mice that were doubly mutant in prostate tissue for Pten and Erk5 (prostate DKO) exhibited a markedly increased median survival with reduced tumor size and proliferation compared to control Pten-mutant mice, the latter of which exhibited increased Erk5 mRNA expression. A comparative transcriptomic analysis revealed upregulation in prostate DKO mice of the chemokines Ccl5 and Cxcl10, two potent chemoattractants for T lymphocytes. Consistent with this effect, we observed a relative increase in a predominantly CD4+ T cell infiltrate in the prostate epithelial and stroma of tumors from DKO mice. Collectively, our results offer a preclinical proof of concept for ERK5 as a target to enhance T cell infiltrates in prostate cancer, with possible implications for leveraging immune therapy in this disease.
http://ift.tt/2rsWAZG
Evolution in Treatment Strategy for Metastatic Spine Disease: Presently Evolving Modalities
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Naresh Kumar, Rishi Malhotra, Aye Sandar Zaw, Karthikeyan Maharajan, Nandika Naresh, Aravind Kumar, Balamurugan Vallayappan
The advent of minimally invasive surgery (MIS) in surgical management armamentarium and stereotactic radiosurgery in the domain of radiotherapy, has led to a major evolution in treatment of metastatic spine disease (MSD). We reviewed the recent literature to discuss evolution from open to MIS approaches in MSD and the concurrent evolution in radiotherapy. This will provide a sound base to further development and understanding of treatment paradigms in MSD. Literature review showed that evolution of surgery can be traced from inappropriate open surgery (i.e. laminectomy) to appropriate open (i.e. posterior instrumentation and decompression) and further to minimally invasive surgery. This transition was interspersed with the introduction of radiotherapy and its evolution in management of MSD. Evidence shows that presently, the best clinical outcomes are achieved by surgery with timely postoperative radiotherapy. To make surgery an appealing choice in MSD, surgical morbidity needs to be minimized, when planning postoperative oncological treatment. MIS approaches are encouraging due to early wound healing resulting in early introduction of radiotherapy, reduced intraoperative blood loss and shortened hospital stay. Pain reduction and neurological improvement are comparable to open surgery. A multidisciplinary team approach including spinal surgeons, medical & radiation oncologists is mandatory, as the treatment options are constantly evolving. Advancement in radiotherapy with introduction of MIS can be a game-changer in MSD due to reduced peri-operative morbidity, allowing earlier postoperative radiotherapy/chemotherapy. We also provide our treatment algorithm which relies on clinical presentation and radiological appearance of spinal cord compression, providing an overview of treatment strategy.
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Does response rate of chemotherapy with molecular target agents correlate with the conversion rate and survival in patients with unresectable colorectal liver metastases?: A systematic review
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 6
Author(s): M. Okuno, E. Hatano, H. Nishino, S. Seo, K. Taura, S. Uemoto
PurposeThis study aimed to evaluate whether the response rate of chemotherapy with molecular target agents correlates with the conversion rate, R0 resection rate, and survival in patients with initially unresectable colorectal liver metastases (CRLM).MethodsWe reviewed the literature of prospective, controlled trials of systemic chemotherapy for patients with unresectable liver-only CRLM, including resectable extrahepatic metastases. Pearson's correlation coefficients were calculated.ResultsA total of 26 patient groups from 18 studies were reviewed. The response rate was significantly correlated with the conversion rate (r = 0.66) and R0 resection rate (r = 0.43) in overall patients. In subgroup analysis, only the conversion rate in patients with chemotherapy only (r = 0.75) and anti-EGFR therapy (r = 0.78) were significantly strongly correlated with the response rate. A non-significant strong trend toward correlation between response and conversion rates was observed in patients with bevacizumab (r = 0.73, p = 0.10). The regression line in the scatter plot of patients using bevacizumab showed a less steep slope. This indicated that conversion rates were relatively less affected by response rates under anti-VEGF therapy compared with the other patient groups. The response rate in chemotherapy-only patients was significantly correlated with median progression-free survival (r = 0.61) and overall survival (r = 0.66).ConclusionsChemotherapy without molecular target agents and with anti-EGFR agents shows similar results of correlation between response and conversion/R0 resection rates. Under anti-VEGF therapy, conversion would be expected, even with a relatively lower response rate.
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Editorial Board
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 6
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Best practice for perioperative management of patients with cytoreductive surgery and HIPEC
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 6
Author(s): C. Raspé, L. Flöther, R. Schneider, M. Bucher, P. Piso
Due to the significantly improved outcome and quality of life of patients with different tumor entities after cytoreductive surgery (CRS) and HIPEC, there is an increasing number of centers performing CRS and HIPEC procedures. As this procedure is technically challenging with potential high morbidity and mortality, respectively, institutional experience also in the anesthetic and intensive care departments is essential for optimal treatment and prevention of adverse events. Clinical pathways have to be developed to achieve also good results in more comorbid patients with border line indications and extensive surgical procedures. The anesthesiologist has deal with relevant fluid, blood and protein losses, increased intraabdominal pressure, systemic hypo-/hyperthermia, and increased metabolic rate in patients undergoing cytoreductive surgery with HIPEC. It is of utmost importance to maintain or restore an adequate volume by aggressive substitution of intravenous fluids, which counteracts the increased fluid loss and venous capacitance during this procedure. Supplementary thoracic epidural analgesia, non-invasive ventilation, and physiotherapy are recommended to guarantee adequate pain therapy and postoperative extubation as well as fast-track concepts. Advanced hemodynamic monitoring is essential to help the anesthesiologist picking up information about the real-time fluid status of the patient. Preoperative preconditioning is mandatory in patients scheduled for HIPEC surgery and will result in improved outcome. Postoperatively, volume status optimization, early nutritional support, sufficient anticoagulation, and point of care coagulation management are essential. This is an extensive update on all relevant topics for anesthetists and intensivists dealing with CRS and HIPEC.
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Announcements
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 6
http://ift.tt/2qxR6fT
Salvage hepatectomy for local recurrence of hepatocellular carcinomas offers survival comparable to that of matched patients who undergo primary hepatectomies
Publication date: June 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 6
Author(s): Y. Kishi, S. Nara, M. Esaki, N. Hiraoka, K. Shimada
BackgroundThe feasibility of salvage hepatectomy for locally recurrent hepatocellular carcinomas (HCCs) is unclear, especially for patients with viable parts of previously multinodular tumors.MethodsWe reviewed charts of patients who underwent initial hepatectomies between 2000 and 2014 to select those with local recurrences (LR) after non-surgical treatments. Their postoperative outcomes, including morbidity, recurrence-free survival (RFS), and overall survival (OS) were compared with matched patients who underwent initial hepatectomies for primary HCCs (PR). Their local recurrence patterns were divided into recurrent solitary tumors (Subgroup A); and recurrent parts of multinodular tumors (Subgroup B).ResultsAmong 664 patients, hepatectomy for LR was performed in 62 patients. Matched 59 patients were selected as PR. Clinicopathologic profiles at initial surgery were comparable between the LR and PR groups. Incidence of major morbidity (LR vs. PR, 7% vs. 5%, P = 1.00), 5-year RFS (21% vs. 37%, P = 0.28), and 5-year OS (69% vs. 69%, P = 0.62) were comparable. In the LR group, Subgroup B showed worse 5-year RFS (A vs. B, 29% vs. 0%, P < 0.01) and 5-year-OS (80% vs. 53%, P = 0.01). Postoperative recurrence occurred in 46 patients, but local and extrahepatic recurrence was seen only in 2 patients and 2 patients, respectively.ConclusionSalvage hepatectomy for locally recurrent HCCs is feasible, and results in prognosis comparable with hepatectomy for primary HCCs. Although the risk of postoperative recurrence was high in Subgroup B, rare local recurrence suggests the usefulness of salvaging uncontrolled tumor by nonsurgical treatment.
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Prognostic impact of macrometastasis linear size in sentinel node biopsy for breast carcinoma
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Maria P. Foschini, Rossella Miglio, Cecily Quinn, Beatrice Belgio, Peter Regitnig, Simonetta Bianchi, Roberto Nannini, Horst Buerger, Handan Kaya, Ildikó Illyés, Janina Kulka, Clive A. Wells, James De Gaetano, Inta Lipeniece-Karele, Gabor Cserni
The aim of the present study was to evaluate the risk of axillary non-sentinel lymph-node metastases (ALN) in breast cancer patients presenting macrometastasis (Mac-m) in the sentinel lymph node (SN).Materials and MethodsA retrospective series of 1464 breast cancers from patients who underwent ALN dissection following the diagnosis of Mac-m in the sentinel node (SN) was studied. In all the cases the MAC-m linear size was evaluated and correlated with presence or absence of non-SN ALN metastases.ResultsNon-SN metastases were detected in 644\1464 cases (43,98%). The risk of further axillary metastases ranged from 20.2% (37/183) in cases with Mac-m between 2-2.9 mm, to 65.3% (262/401) in cases with Mac-m measuring > 10 mm. The risk of non-SN ALN metastases showed a 3% increase, parallel to each mm increment in SN metastasis size. The data evaluated with the receiver operating characteristic (ROC) curve showed that the Mac-m could be subdivided according to a new cut-off of 7 mm. pT1 tumours, with Mac-m < 7 mm had a risk of non-SN ALN metastases of <30%. Furthermore 109/127 of these (85.8%) had 3 or less non-SN ALN -metastases.ConclusionsThe present data give a detailed description on the risk of non-SN ALN involvement, that may be useful in the evaluation of breast cancer patients. It is suggested that a Mac-m size of < 7 mm is related to a low residual axillary disease burden in breast cancer patients with small (pT1) tumours.
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Calendar
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 6
http://ift.tt/2pMCble
APJ Is Associated with Treatment Response in Gastric Cancer Patients Receiving Concurrent Chemoradiotherapy and Endostar Therapy
Cancer Biotherapy & Radiopharmaceuticals May 2017, Vol. 32, No. 4: 133-138.
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Cancer Biotherapy: More Than Immunotherapy
Cancer Biotherapy & Radiopharmaceuticals May 2017, Vol. 32, No. 4: 111-114.
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Circadian Gene CLOCK Affects Drug-Resistant Gene Expression and Cell Proliferation in Ovarian Cancer SKOV3/DDP Cell Lines Through Autophagy
Cancer Biotherapy & Radiopharmaceuticals May 2017, Vol. 32, No. 4: 139-146.
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Clinical Significance and Tumor-Suppressive Function of miR-516b in Nonsmall Cell Lung Cancer
Cancer Biotherapy & Radiopharmaceuticals May 2017, Vol. 32, No. 4: 115-123.
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First-in-Human PET/CT Imaging of Metastatic Neuroendocrine Neoplasms with Cyclotron-Produced 44Sc-DOTATOC: A Proof-of-Concept Study
Cancer Biotherapy & Radiopharmaceuticals May 2017, Vol. 32, No. 4: 124-132.
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Cancer Biotherapy: More Than Immunotherapy
Cancer Biotherapy & Radiopharmaceuticals May 2017, Vol. 32, No. 4: 111-114.
http://ift.tt/2qSFVBQ
Circadian Gene CLOCK Affects Drug-Resistant Gene Expression and Cell Proliferation in Ovarian Cancer SKOV3/DDP Cell Lines Through Autophagy
Cancer Biotherapy & Radiopharmaceuticals May 2017, Vol. 32, No. 4: 139-146.
http://ift.tt/2rslite
Clinical Significance and Tumor-Suppressive Function of miR-516b in Nonsmall Cell Lung Cancer
Cancer Biotherapy & Radiopharmaceuticals May 2017, Vol. 32, No. 4: 115-123.
http://ift.tt/2qSD3oc
APJ Is Associated with Treatment Response in Gastric Cancer Patients Receiving Concurrent Chemoradiotherapy and Endostar Therapy
Cancer Biotherapy & Radiopharmaceuticals May 2017, Vol. 32, No. 4: 133-138.
http://ift.tt/2rsfLCO
First-in-Human PET/CT Imaging of Metastatic Neuroendocrine Neoplasms with Cyclotron-Produced 44Sc-DOTATOC: A Proof-of-Concept Study
Cancer Biotherapy & Radiopharmaceuticals May 2017, Vol. 32, No. 4: 124-132.
http://ift.tt/2qSKUSM
In reply to Chang et al.: Contouring guidelines for post-mastectomy radiotherapy a cry for international consensus
We congratulate Chang et al. for their recent publication detailing patterns of locoregional recurrence for breast cancer patients in the context of cooperative group contouring guidelines from RTOG and ESTRO [1]. The number of patients suffering recurrence outside of the smaller ESTRO but within the larger RTOG volumes was small for patients undergoing breast conserving surgery (3.6%), suggesting good concordance between the CTV volume recommendations; however, a significant percentage (28.9%) of local failures after mastectomy occurred outside of the smaller ESTRO but within the larger RTOG volumes.
http://ift.tt/2pMyMm6
Gilteritinib, a FLT3/AXL inhibitor, shows antileukemic activity in mouse models of FLT3 mutated acute myeloid leukemia
Summary
Advances in the understanding of the molecular basis for acute myeloid leukemia (AML) have generated new potential targets for treatment. Fms-like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes in AML and mutations in this gene are associated with poor overall survival. AXL plays a role in the activation of FLT3 and has been implicated in the pathogenesis of AML. The studies reported here evaluated the ability of a novel FLT3/AXL inhibitor, gilteritinib, to block mutated FLT3 in cellular and animal models of AML. Initial kinase studies showed that gilteritinib, a type I tyrosine kinase inhibitor, was highly selective for both FLT3 and AXL while having weak activity against c-KIT. Gilteritinib demonstrated potent inhibitory activity against the internal tandem duplication (FLT3-ITD) and FLT3-D835Y point mutations in cellular assays using MV4–11 and MOLM-13 cells as well as Ba/F3 cells expressing mutated FLT3. Gilteritinib also inhibited FLT3-F691 mutations, although to a lesser degree, in these assays. Furthermore, gilteritinib decreased the phosphorylation levels of FLT3 and its downstream targets in both cellular and animal models. In vivo, gilteritinib was distributed at high levels in xenografted tumors after oral administration. The decreased FLT3 activity and high intratumor distribution of gilteritinib translated to tumor regression and improved survival in xenograft and intra-bone marrow transplantation models of FLT3-driven AML. No overt toxicity was seen in mouse models treated with gilteritinib. These results indicate that gilteritinib may be an important next-generation FLT3 inhibitor for use in the treatment of FLT3 mutation-positive AML.
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Gilteritinib, a FLT3/AXL inhibitor, shows antileukemic activity in mouse models of FLT3 mutated acute myeloid leukemia
Summary
Advances in the understanding of the molecular basis for acute myeloid leukemia (AML) have generated new potential targets for treatment. Fms-like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes in AML and mutations in this gene are associated with poor overall survival. AXL plays a role in the activation of FLT3 and has been implicated in the pathogenesis of AML. The studies reported here evaluated the ability of a novel FLT3/AXL inhibitor, gilteritinib, to block mutated FLT3 in cellular and animal models of AML. Initial kinase studies showed that gilteritinib, a type I tyrosine kinase inhibitor, was highly selective for both FLT3 and AXL while having weak activity against c-KIT. Gilteritinib demonstrated potent inhibitory activity against the internal tandem duplication (FLT3-ITD) and FLT3-D835Y point mutations in cellular assays using MV4–11 and MOLM-13 cells as well as Ba/F3 cells expressing mutated FLT3. Gilteritinib also inhibited FLT3-F691 mutations, although to a lesser degree, in these assays. Furthermore, gilteritinib decreased the phosphorylation levels of FLT3 and its downstream targets in both cellular and animal models. In vivo, gilteritinib was distributed at high levels in xenografted tumors after oral administration. The decreased FLT3 activity and high intratumor distribution of gilteritinib translated to tumor regression and improved survival in xenograft and intra-bone marrow transplantation models of FLT3-driven AML. No overt toxicity was seen in mouse models treated with gilteritinib. These results indicate that gilteritinib may be an important next-generation FLT3 inhibitor for use in the treatment of FLT3 mutation-positive AML.
http://ift.tt/2qs8YL3
Gynecological brachytherapy for postoperative endometrial cancer: dosimetric analysis (Ir-192 vs Co-60)
Abstract
Introduction
Endovaginal brachytherapy treatment dosimetry differences were studied using Ir-192 or Co-60 sources for postoperative endometrial cancer.
Materials and methods
A prospective descriptive study was conducted. Thirty-six dosimetry plans of different patients were studied (15 by Ir-192 and 21 by Co-60). Variables studied included D2cc Rectum, D2cc Bladder, D2cc Sigmoid, dose percentage at point 0 (applicator surface on the top of the cylinder) and dose percentage at point 1 (5 mm deep on the top of the cylinder). A comparative analysis was performed of the values obtained from each variable between Ir-192 and Co-60 treatments. We compared average of each variables between Iridium and Cobalt by T Student for independent samples (SPSS 22).
Results
There were no significant differences on using Ir-192 or Co-60 by variables, except for dose percentage at point 1 in which we detected significant differences (Table 1).
The results
Variables
Sources
Iridium 192
Cobalt 60
D2cc Rectum
(mean dose)
[rank]
6.01 Gy [3.99–7.90]
5.28 Gy [3.87–6,34]
D2cc Bladder
(mean dose)
[rank]
5.82 Gy [4.20–8.38]
5.05 Gy [2.23–6.95]
D2cc Sigmoid
(mean dose)
[rank]
4.43 Gy [1.66–6.67]
2.33 Gy [0.60–4.28]
Dose percentage at point 0a
(mean)
[rank]
210.74% [120.90–234.90]
204.75% [177.10–223]
Dose percentage at point 1b
(mean)
[rank]
93.49% [87.30–100.60]
100.11% [96.70–102]
aPoint 0: point to the applicator surface
bPoint 1: point to 5 mm applicator surface
Discussion
Brachytherapy treatment dosimetry plans are similar using Ir-192 or Co-60, except dose percentage at point 1. In the scientific literature, some differences exist and there are some advantages in using cobalt.
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Hangeshashinto (TJ-14) prevents radiation-induced mucositis by suppressing cyclooxygenase-2 expression and chemotaxis of inflammatory cells
Abstract
Purpose
Radiation-induced oral mucositis is the most common side effect of radiotherapy in head and neck cancer; however, effective modalities for its prevention have not been established. In this study, we evaluated the effectiveness of Hangeshashinto (TJ-14), a Japanese herbal medicine, for preventing radiation-induced mucositis and elucidated its effect on inflammatory responses, including inflammatory cell chemotaxis and cyclooxygenase-2 (COX2) expression, in an animal model.
Methods
Syrian hamsters, 8–9 weeks old, were enrolled in this study. Animals were irradiated with a single 40 Gy dose to the buccal mucosa. Hamsters freely received a treatment diet mixed with 2% TJ-14 or a normal diet daily. The therapeutic effect was determined based on the visual mucositis score, body weight, and histological examination of infiltrated neutrophils and COX2 expression.
Results
TJ-14 significantly reduced the severity of mucositis. The percentage with severe mucositis (score ≥3) was 100% in the untreated group and 16.7% in the TJ-14 group (P < 0.05). There was no difference in body weight change between the groups; however, weight gain in the untreated group tended to be suppressed compared to that in the TJ-14 group during the peak period of mucositis. In addition, TJ-14 inhibited the infiltration of neutrophils and COX2 expression in irradiated mucosa (P < 0.05).
Conclusions
TJ-14 reduced the severity of mucositis in an animal model by suppressing the inflammatory response. Because TJ-14 is inexpensive and its safety is established, it is a promising candidate for the standard treatment of radiation-induced mucositis in cancer patients.
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Gynecological brachytherapy for postoperative endometrial cancer: dosimetric analysis (Ir-192 vs Co-60)
Abstract
Introduction
Endovaginal brachytherapy treatment dosimetry differences were studied using Ir-192 or Co-60 sources for postoperative endometrial cancer.
Materials and methods
A prospective descriptive study was conducted. Thirty-six dosimetry plans of different patients were studied (15 by Ir-192 and 21 by Co-60). Variables studied included D2cc Rectum, D2cc Bladder, D2cc Sigmoid, dose percentage at point 0 (applicator surface on the top of the cylinder) and dose percentage at point 1 (5 mm deep on the top of the cylinder). A comparative analysis was performed of the values obtained from each variable between Ir-192 and Co-60 treatments. We compared average of each variables between Iridium and Cobalt by T Student for independent samples (SPSS 22).
Results
There were no significant differences on using Ir-192 or Co-60 by variables, except for dose percentage at point 1 in which we detected significant differences (Table 1).
The results
Variables
Sources
Iridium 192
Cobalt 60
D2cc Rectum
(mean dose)
[rank]
6.01 Gy [3.99–7.90]
5.28 Gy [3.87–6,34]
D2cc Bladder
(mean dose)
[rank]
5.82 Gy [4.20–8.38]
5.05 Gy [2.23–6.95]
D2cc Sigmoid
(mean dose)
[rank]
4.43 Gy [1.66–6.67]
2.33 Gy [0.60–4.28]
Dose percentage at point 0a
(mean)
[rank]
210.74% [120.90–234.90]
204.75% [177.10–223]
Dose percentage at point 1b
(mean)
[rank]
93.49% [87.30–100.60]
100.11% [96.70–102]
aPoint 0: point to the applicator surface
bPoint 1: point to 5 mm applicator surface
Discussion
Brachytherapy treatment dosimetry plans are similar using Ir-192 or Co-60, except dose percentage at point 1. In the scientific literature, some differences exist and there are some advantages in using cobalt.
http://ift.tt/2pXJqSh
Hangeshashinto (TJ-14) prevents radiation-induced mucositis by suppressing cyclooxygenase-2 expression and chemotaxis of inflammatory cells
Abstract
Purpose
Radiation-induced oral mucositis is the most common side effect of radiotherapy in head and neck cancer; however, effective modalities for its prevention have not been established. In this study, we evaluated the effectiveness of Hangeshashinto (TJ-14), a Japanese herbal medicine, for preventing radiation-induced mucositis and elucidated its effect on inflammatory responses, including inflammatory cell chemotaxis and cyclooxygenase-2 (COX2) expression, in an animal model.
Methods
Syrian hamsters, 8–9 weeks old, were enrolled in this study. Animals were irradiated with a single 40 Gy dose to the buccal mucosa. Hamsters freely received a treatment diet mixed with 2% TJ-14 or a normal diet daily. The therapeutic effect was determined based on the visual mucositis score, body weight, and histological examination of infiltrated neutrophils and COX2 expression.
Results
TJ-14 significantly reduced the severity of mucositis. The percentage with severe mucositis (score ≥3) was 100% in the untreated group and 16.7% in the TJ-14 group (P < 0.05). There was no difference in body weight change between the groups; however, weight gain in the untreated group tended to be suppressed compared to that in the TJ-14 group during the peak period of mucositis. In addition, TJ-14 inhibited the infiltration of neutrophils and COX2 expression in irradiated mucosa (P < 0.05).
Conclusions
TJ-14 reduced the severity of mucositis in an animal model by suppressing the inflammatory response. Because TJ-14 is inexpensive and its safety is established, it is a promising candidate for the standard treatment of radiation-induced mucositis in cancer patients.
http://ift.tt/2qsVLBH
Index
Source:Anesthesiology Clinics, Volume 35, Issue 2
http://ift.tt/2qsKtxm
Copyright
Source:Anesthesiology Clinics, Volume 35, Issue 2
http://ift.tt/2pXy2G7
Contributors
Source:Anesthesiology Clinics, Volume 35, Issue 2
http://ift.tt/2qsBzjo
Contents
Publication date: June 2017
Source:Anesthesiology Clinics, Volume 35, Issue 2
http://ift.tt/2pXGpkT
Forthcoming Issues
Source:Anesthesiology Clinics, Volume 35, Issue 2
http://ift.tt/2qsV9f9
Pharmacology
Source:Anesthesiology Clinics, Volume 35, Issue 2
Author(s): Lee A. Fleisher
http://ift.tt/2pXySTt
Pharmacology
Source:Anesthesiology Clinics, Volume 35, Issue 2
Author(s): Alan D. Kaye
http://ift.tt/2qsVLSd
The Future of Pharmacology in Anesthesia Practice
Source:Anesthesiology Clinics, Volume 35, Issue 2
Author(s): Alan D. Kaye
http://ift.tt/2pXlmiC
Anticoagulation and Neuraxial/Peripheral Anesthesia
Source:Anesthesiology Clinics, Volume 35, Issue 2
Author(s): Mudit Kaushal, Ryan E. Rubin, Alan D. Kaye, Karina Gritsenko
Teaser
Novel anticoagulants (NAGs) have emerged as the preferred alternatives to vitamin K antagonists. In patients being considered for regional anesthesia, these drugs present a layer of complexity in the preprocedure evaluation. There are no established tests to monitor anticoagulant activity and our experience is short with these drugs. These authors believe it is important to review the relevant hematology, orthopedics, and anesthesiology literature to provide a valuable reference for the clinician who is met with these challenges. In addition to discussing NAGs, we also review the existing American Society of Regional Anesthesia guidelines for heparin, low-molecular-weight heparin, and antiplatelet agents.http://ift.tt/2qsVjmM
Pharmacology of Antiemetics
Source:Anesthesiology Clinics, Volume 35, Issue 2
Author(s): Alan D. Kaye, Elyse M. Cornett, John Chalabi, Natale Z. Naim, Matthew B. Novitch, Justin B. Creel, Preya Jhita, Thomas N. Trang, Jacquelyn R. Paetzold, Nicholas Darensburg, Burton D. Beakley, Richard D. Urman
Teaser
Postoperative nausea and vomiting (PONV) is associated with delayed recovery and dissatisfaction after surgical procedures. A key component to management is identifying risk factors and high-risk populations. Advances in pharmacologic therapeutics have resulted in agents targeting different pathways associated with the mediation of nausea and vomiting. This review focuses on these agents and the clinical aspects of their use in patients postoperatively. Combination therapies are reviewed, and studies demonstrate that when 2 or more antiemetic agents acting on different receptors are used, an overall improved efficacy is demonstrated when compared with a single agent alone in patients.http://ift.tt/2pXwDPT
Pharmacology of Octreotide
Source:Anesthesiology Clinics, Volume 35, Issue 2
Author(s): Reza M. Borna, Jonathan S. Jahr, Susanna Kmiecik, Ken F. Mancuso, Alan D. Kaye
Teaser
Many patients presenting with a history of foregut, midgut neuroendocrine tumors (NETs) or carcinoid syndrome can experience life-threatening carcinoid crises during anesthesia or surgery. Clinicians should understand the pharmacology of octreotide and appreciate the use of continuous infusions of high-dose octreotide, which can minimize intraoperative carcinoid crises. We administer a prophylactic 500-μg bolus of octreotide intravenously (IV) and begin a continuous infusion of 500 μg/h for all NET patients. Advantages include low cost and excellent safety profile. High-dose octreotide for midgut and foregut NETs requires an appreciation of the pathophysiology involved in the disease, pharmacology, drug–drug interactions, and side effects.http://ift.tt/2qsY6fN
Perioperative Pharmacologic Considerations in Obesity
Source:Anesthesiology Clinics, Volume 35, Issue 2
Author(s): Simon Willis, Gregory J. Bordelon, Maunak V. Rana
Teaser
Obesity has increased in incidence worldwide. Along with the increased number of obese patients, comorbid conditions are also more prevalent in this population. Obesity leads to changes in the physiology of patients along with an altered response to pharmacologic therapy. Vigilant perioperative physicians must be aware of the unique characteristics of administered agents in order to appropriately provide anesthetic care for obese patients. Because of the variability in tissue content in obese patients and changes in pharmacokinetic modeling, a one-size-fits-all approach is not justified and a more sophisticated and prudent approach is indicated.http://ift.tt/2pXJstn
Pharmacogenomics in Anesthesia
Source:Anesthesiology Clinics, Volume 35, Issue 2
Author(s): Ramsey Saba, Alan D. Kaye, Richard D. Urman
Teaser
A significant number of commonly administered medications in anesthesia show wide clinical interpatient variability. Some of these include neuromuscular blockers, opioids, local anesthetics, and inhalation anesthetics. Individual genetic makeup may account for and predict cardiovascular outcomes after cardiac surgery. These interactions can manifest at any point in the perioperative period and may also only affect a specific system. A better understanding of pharmacogenomics will allow for more individually tailored anesthetics and may ultimately lead to better outcomes, decreased hospital stays, and improved patient satisfaction.http://ift.tt/2qt1Rlv
Pharmacogenomics in Pain Management
Source:Anesthesiology Clinics, Volume 35, Issue 2
Author(s): Ramsey Saba, Alan D. Kaye, Richard D. Urman
Teaser
There is interpatient variability to analgesic administration. Much can be traced to pharmacogenomics variations between individuals. Certain ethnicities are more prone to reduced function of CYP2D6. Weak opioids are subject to interpatient variation based on their CYP2D6 type. Strong opioids have variations based on their transport and individual metabolism. Several cytochrome enzymes have been found to be involved with ketamine but there is no strong evidence of individual polymorphisms manifesting in clinical outcomes. Nonsteroidal anti-inflammatory drugs have adverse outcomes that certain CYP variants are more prone toward. There are now recommendations for dosing based on specific genomic makeup.http://ift.tt/2qxrQGD
Essential Elements of Multimodal Analgesia in Enhanced Recovery After Surgery (ERAS) Guidelines
Source:Anesthesiology Clinics, Volume 35, Issue 2
Author(s): Anair Beverly, Alan D. Kaye, Olle Ljungqvist, Richard D. Urman
Teaser
Perioperative multimodal analgesia uses combinations of analgesic medications that act on different sites and pathways in an additive or synergistic manner to achieve pain relief with minimal or no opiate consumption. Although all medications have side effects, opiates have particularly concerning, multisystemic, long-term, and short-term side effects, which increase morbidity and prolong admissions. Enhanced recovery is a systematic process addressing each aspect affecting recovery. This article outlines the evidence base forming the current multimodal analgesia recommendations made by the Enhanced Recovery After Surgery Society (ERAS). We describe current evidence and important future directions for effective perioperative multimodal analgesia in enhanced recovery pathways.http://ift.tt/2pMlxlz
Gynecological brachytherapy for postoperative endometrial cancer: dosimetric analysis (Ir-192 vs Co-60)
Abstract
Introduction
Endovaginal brachytherapy treatment dosimetry differences were studied using Ir-192 or Co-60 sources for postoperative endometrial cancer.
Materials and methods
A prospective descriptive study was conducted. Thirty-six dosimetry plans of different patients were studied (15 by Ir-192 and 21 by Co-60). Variables studied included D2cc Rectum, D2cc Bladder, D2cc Sigmoid, dose percentage at point 0 (applicator surface on the top of the cylinder) and dose percentage at point 1 (5 mm deep on the top of the cylinder). A comparative analysis was performed of the values obtained from each variable between Ir-192 and Co-60 treatments. We compared average of each variables between Iridium and Cobalt by T Student for independent samples (SPSS 22).
Results
There were no significant differences on using Ir-192 or Co-60 by variables, except for dose percentage at point 1 in which we detected significant differences (Table 1).
The results
Variables
Sources
Iridium 192
Cobalt 60
D2cc Rectum
(mean dose)
[rank]
6.01 Gy [3.99–7.90]
5.28 Gy [3.87–6,34]
D2cc Bladder
(mean dose)
[rank]
5.82 Gy [4.20–8.38]
5.05 Gy [2.23–6.95]
D2cc Sigmoid
(mean dose)
[rank]
4.43 Gy [1.66–6.67]
2.33 Gy [0.60–4.28]
Dose percentage at point 0a
(mean)
[rank]
210.74% [120.90–234.90]
204.75% [177.10–223]
Dose percentage at point 1b
(mean)
[rank]
93.49% [87.30–100.60]
100.11% [96.70–102]
aPoint 0: point to the applicator surface
bPoint 1: point to 5 mm applicator surface
Discussion
Brachytherapy treatment dosimetry plans are similar using Ir-192 or Co-60, except dose percentage at point 1. In the scientific literature, some differences exist and there are some advantages in using cobalt.
http://ift.tt/2pXJqSh
Hangeshashinto (TJ-14) prevents radiation-induced mucositis by suppressing cyclooxygenase-2 expression and chemotaxis of inflammatory cells
Abstract
Purpose
Radiation-induced oral mucositis is the most common side effect of radiotherapy in head and neck cancer; however, effective modalities for its prevention have not been established. In this study, we evaluated the effectiveness of Hangeshashinto (TJ-14), a Japanese herbal medicine, for preventing radiation-induced mucositis and elucidated its effect on inflammatory responses, including inflammatory cell chemotaxis and cyclooxygenase-2 (COX2) expression, in an animal model.
Methods
Syrian hamsters, 8–9 weeks old, were enrolled in this study. Animals were irradiated with a single 40 Gy dose to the buccal mucosa. Hamsters freely received a treatment diet mixed with 2% TJ-14 or a normal diet daily. The therapeutic effect was determined based on the visual mucositis score, body weight, and histological examination of infiltrated neutrophils and COX2 expression.
Results
TJ-14 significantly reduced the severity of mucositis. The percentage with severe mucositis (score ≥3) was 100% in the untreated group and 16.7% in the TJ-14 group (P < 0.05). There was no difference in body weight change between the groups; however, weight gain in the untreated group tended to be suppressed compared to that in the TJ-14 group during the peak period of mucositis. In addition, TJ-14 inhibited the infiltration of neutrophils and COX2 expression in irradiated mucosa (P < 0.05).
Conclusions
TJ-14 reduced the severity of mucositis in an animal model by suppressing the inflammatory response. Because TJ-14 is inexpensive and its safety is established, it is a promising candidate for the standard treatment of radiation-induced mucositis in cancer patients.
http://ift.tt/2qsVLBH
Gynecological brachytherapy for postoperative endometrial cancer: dosimetric analysis (Ir-192 vs Co-60)
Abstract
Introduction
Endovaginal brachytherapy treatment dosimetry differences were studied using Ir-192 or Co-60 sources for postoperative endometrial cancer.
Materials and methods
A prospective descriptive study was conducted. Thirty-six dosimetry plans of different patients were studied (15 by Ir-192 and 21 by Co-60). Variables studied included D2cc Rectum, D2cc Bladder, D2cc Sigmoid, dose percentage at point 0 (applicator surface on the top of the cylinder) and dose percentage at point 1 (5 mm deep on the top of the cylinder). A comparative analysis was performed of the values obtained from each variable between Ir-192 and Co-60 treatments. We compared average of each variables between Iridium and Cobalt by T Student for independent samples (SPSS 22).
Results
There were no significant differences on using Ir-192 or Co-60 by variables, except for dose percentage at point 1 in which we detected significant differences (Table 1).
The results
Variables
Sources
Iridium 192
Cobalt 60
D2cc Rectum
(mean dose)
[rank]
6.01 Gy [3.99–7.90]
5.28 Gy [3.87–6,34]
D2cc Bladder
(mean dose)
[rank]
5.82 Gy [4.20–8.38]
5.05 Gy [2.23–6.95]
D2cc Sigmoid
(mean dose)
[rank]
4.43 Gy [1.66–6.67]
2.33 Gy [0.60–4.28]
Dose percentage at point 0a
(mean)
[rank]
210.74% [120.90–234.90]
204.75% [177.10–223]
Dose percentage at point 1b
(mean)
[rank]
93.49% [87.30–100.60]
100.11% [96.70–102]
aPoint 0: point to the applicator surface
bPoint 1: point to 5 mm applicator surface
Discussion
Brachytherapy treatment dosimetry plans are similar using Ir-192 or Co-60, except dose percentage at point 1. In the scientific literature, some differences exist and there are some advantages in using cobalt.
from Cancer via ola Kala on Inoreader http://ift.tt/2pXJqSh
via IFTTT
Hangeshashinto (TJ-14) prevents radiation-induced mucositis by suppressing cyclooxygenase-2 expression and chemotaxis of inflammatory cells
Abstract
Purpose
Radiation-induced oral mucositis is the most common side effect of radiotherapy in head and neck cancer; however, effective modalities for its prevention have not been established. In this study, we evaluated the effectiveness of Hangeshashinto (TJ-14), a Japanese herbal medicine, for preventing radiation-induced mucositis and elucidated its effect on inflammatory responses, including inflammatory cell chemotaxis and cyclooxygenase-2 (COX2) expression, in an animal model.
Methods
Syrian hamsters, 8–9 weeks old, were enrolled in this study. Animals were irradiated with a single 40 Gy dose to the buccal mucosa. Hamsters freely received a treatment diet mixed with 2% TJ-14 or a normal diet daily. The therapeutic effect was determined based on the visual mucositis score, body weight, and histological examination of infiltrated neutrophils and COX2 expression.
Results
TJ-14 significantly reduced the severity of mucositis. The percentage with severe mucositis (score ≥3) was 100% in the untreated group and 16.7% in the TJ-14 group (P < 0.05). There was no difference in body weight change between the groups; however, weight gain in the untreated group tended to be suppressed compared to that in the TJ-14 group during the peak period of mucositis. In addition, TJ-14 inhibited the infiltration of neutrophils and COX2 expression in irradiated mucosa (P < 0.05).
Conclusions
TJ-14 reduced the severity of mucositis in an animal model by suppressing the inflammatory response. Because TJ-14 is inexpensive and its safety is established, it is a promising candidate for the standard treatment of radiation-induced mucositis in cancer patients.
from Cancer via ola Kala on Inoreader http://ift.tt/2qsVLBH
via IFTTT
Cancer Biotherapy: More Than Immunotherapy
Cancer Biotherapy & Radiopharmaceuticals May 2017, Vol. 32, No. 4: 111-114.
http://ift.tt/2qSFVBQ
Circadian Gene CLOCK Affects Drug-Resistant Gene Expression and Cell Proliferation in Ovarian Cancer SKOV3/DDP Cell Lines Through Autophagy
Cancer Biotherapy & Radiopharmaceuticals May 2017, Vol. 32, No. 4: 139-146.
http://ift.tt/2rslite
Clinical Significance and Tumor-Suppressive Function of miR-516b in Nonsmall Cell Lung Cancer
Cancer Biotherapy & Radiopharmaceuticals May 2017, Vol. 32, No. 4: 115-123.
http://ift.tt/2qSD3oc
APJ Is Associated with Treatment Response in Gastric Cancer Patients Receiving Concurrent Chemoradiotherapy and Endostar Therapy
Cancer Biotherapy & Radiopharmaceuticals May 2017, Vol. 32, No. 4: 133-138.
http://ift.tt/2rsfLCO
First-in-Human PET/CT Imaging of Metastatic Neuroendocrine Neoplasms with Cyclotron-Produced 44Sc-DOTATOC: A Proof-of-Concept Study
Cancer Biotherapy & Radiopharmaceuticals May 2017, Vol. 32, No. 4: 124-132.
http://ift.tt/2qSKUSM
Defining optimal cutoff value of MGMT promoter methylation by ROC analysis for clinical setting in glioblastoma patients
Abstract
Resistance to temozolomide (TMZ) chemotherapy poses a significant challenge in the treatment of glioblastoma (GBM). Hypermethylation in O6-methylguanine-DNA methyltransferase (MGMT) promoter is thought to play a critical role in this resistance. Pyrosequencing (PSQ) has been shown to be accurate and robust for MGMT promoter methylation testing. The unresolved issue is the determination of a cut-off value for dichotomization of quantitative MGMT PSQ results into "MGMT methylated" and "MGMT unmethylated" patient subgroups as a basis for further treatment decisions. In this study, receiver operating characteristic (ROC) curve analysis was used to identify an optimal cutoff of MGMT promoter methylation by testing mean percentage of methylation of 4 CpG islands (76–79) within MGMT exon 1. The area under the ROC (AUC) as well as the best cutoff to classify the methylation were calculated. Positive likelihood ratio (LR+) was chosen as a diagnostic parameter for defining an optimal cut-off. Meanwhile, we also analyzed whether mean percentage of methylation at the investigated CpG islands could be regarded as a marker for evaluating prognostication. ROC analysis showed that the optimal threshold was 12.5% (sensitivity: 60.87%; specificity: 76%) in response to the largest LR+ 2.54. 12.5% was established to distinguish MGMT promoter methylation, which was confirmed using validation set. According to the cutoff value, the MGMT promoter methylation was found in 58.3% of GBM. Mean methylation level of the investigated CpG sites strong correlated with overall survival (OS), which means GBM patients with a high level of methylation survived longer than those with low level of methylation(log-rank test, P = 0.017). In conclusion, ROC curve analysis enables the best cutoff for discriminating MGMT promoter methylation status. LR+ can be used as a key factor that evaluates cutoff. The promoter methylation level of MGMT by PSQ in GBM patients had prognostic value.
from Cancer via ola Kala on Inoreader http://ift.tt/2rsbCyU
via IFTTT
Defining optimal cutoff value of MGMT promoter methylation by ROC analysis for clinical setting in glioblastoma patients
Abstract
Resistance to temozolomide (TMZ) chemotherapy poses a significant challenge in the treatment of glioblastoma (GBM). Hypermethylation in O6-methylguanine-DNA methyltransferase (MGMT) promoter is thought to play a critical role in this resistance. Pyrosequencing (PSQ) has been shown to be accurate and robust for MGMT promoter methylation testing. The unresolved issue is the determination of a cut-off value for dichotomization of quantitative MGMT PSQ results into "MGMT methylated" and "MGMT unmethylated" patient subgroups as a basis for further treatment decisions. In this study, receiver operating characteristic (ROC) curve analysis was used to identify an optimal cutoff of MGMT promoter methylation by testing mean percentage of methylation of 4 CpG islands (76–79) within MGMT exon 1. The area under the ROC (AUC) as well as the best cutoff to classify the methylation were calculated. Positive likelihood ratio (LR+) was chosen as a diagnostic parameter for defining an optimal cut-off. Meanwhile, we also analyzed whether mean percentage of methylation at the investigated CpG islands could be regarded as a marker for evaluating prognostication. ROC analysis showed that the optimal threshold was 12.5% (sensitivity: 60.87%; specificity: 76%) in response to the largest LR+ 2.54. 12.5% was established to distinguish MGMT promoter methylation, which was confirmed using validation set. According to the cutoff value, the MGMT promoter methylation was found in 58.3% of GBM. Mean methylation level of the investigated CpG sites strong correlated with overall survival (OS), which means GBM patients with a high level of methylation survived longer than those with low level of methylation(log-rank test, P = 0.017). In conclusion, ROC curve analysis enables the best cutoff for discriminating MGMT promoter methylation status. LR+ can be used as a key factor that evaluates cutoff. The promoter methylation level of MGMT by PSQ in GBM patients had prognostic value.
from Cancer via ola Kala on Inoreader http://ift.tt/2rsbCyU
via IFTTT
Defining optimal cutoff value of MGMT promoter methylation by ROC analysis for clinical setting in glioblastoma patients
Abstract
Resistance to temozolomide (TMZ) chemotherapy poses a significant challenge in the treatment of glioblastoma (GBM). Hypermethylation in O6-methylguanine-DNA methyltransferase (MGMT) promoter is thought to play a critical role in this resistance. Pyrosequencing (PSQ) has been shown to be accurate and robust for MGMT promoter methylation testing. The unresolved issue is the determination of a cut-off value for dichotomization of quantitative MGMT PSQ results into "MGMT methylated" and "MGMT unmethylated" patient subgroups as a basis for further treatment decisions. In this study, receiver operating characteristic (ROC) curve analysis was used to identify an optimal cutoff of MGMT promoter methylation by testing mean percentage of methylation of 4 CpG islands (76–79) within MGMT exon 1. The area under the ROC (AUC) as well as the best cutoff to classify the methylation were calculated. Positive likelihood ratio (LR+) was chosen as a diagnostic parameter for defining an optimal cut-off. Meanwhile, we also analyzed whether mean percentage of methylation at the investigated CpG islands could be regarded as a marker for evaluating prognostication. ROC analysis showed that the optimal threshold was 12.5% (sensitivity: 60.87%; specificity: 76%) in response to the largest LR+ 2.54. 12.5% was established to distinguish MGMT promoter methylation, which was confirmed using validation set. According to the cutoff value, the MGMT promoter methylation was found in 58.3% of GBM. Mean methylation level of the investigated CpG sites strong correlated with overall survival (OS), which means GBM patients with a high level of methylation survived longer than those with low level of methylation(log-rank test, P = 0.017). In conclusion, ROC curve analysis enables the best cutoff for discriminating MGMT promoter methylation status. LR+ can be used as a key factor that evaluates cutoff. The promoter methylation level of MGMT by PSQ in GBM patients had prognostic value.
http://ift.tt/2rsbCyU
Immunothérapie et radiothérapie
Source:Cancer/Radiothérapie
Author(s): S. Bockel, D. Antoni, É. Deutsch, F. Mornex
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Immunothérapie et radiothérapie
Source:Cancer/Radiothérapie
Author(s): S. Bockel, D. Antoni, É. Deutsch, F. Mornex
http://ift.tt/2rghMoy
TUmor-volume to breast-volume RAtio for improving COSmetic results in breast cancer patients (TURACOS); a randomized controlled trial
Abstract
Background
Cosmetic result following breast conserving surgery (BCS) for cancer influences quality of life and psychosocial functioning in breast cancer patients. A preoperative prediction of expected cosmetic result following BCS is not (yet) standard clinical practice and therefore the choice for either mastectomy or BCS is still subjective. Recently, we showed that tumour volume to breast volume ratio as well as tumour location in the breast are independent predictors of superior cosmetic result following BCS. Implementation of a prediction model including both factors, has not been studied in a prospective manner. This study aims to improve cosmetic outcome by implementation of a prediction model in the treatment decision making for breast cancer patients opting for BCS.
Methods/design
Multicentre, single-blinded, randomized controlled trial comparing standard preoperative work-up to a preoperative work-up with addition of the prediction model. Tumour volume to breast volume ratio and tumour location in the breast will be used to predict cosmetic outcome in invasive breast cancer patients opting for BCS. Three dimensional (3D)-ultrasonography will be used to measure the tumour volume to breast volume ratio needed for the prediction model. Sample size was estimated based on a 14% improvement in incidence of superior cosmetic result one year after BCS (71% in the control group versus 85% in the intervention group). Primarily cosmetic outcome will be evaluated by a 6-member independent panel. Secondary endpoints include; (1) patient reported outcome measured by BREAST-Q, EORTC-QLQ-C30/BR23 and EQ-5D-5 L (2) cosmetic outcome as assessed through the BCCT.core software, (3) radiation-induced reaction (4) surgical treatment performed, (5) pathological result and (6) cost-effectiveness. Follow-up data will be collected for 3 years after surgery or finishing radiotherapy.
Discussion
This randomized controlled trial examines the value of a preoperative prediction model for the treatment-decision making. It aims for a superior cosmetic result in breast cancer patients opting for BCS. We expect improvement of patients' quality of life and psychosocial functioning in a cost-effective way.
Trial registration
Prospectively registered, February 17th 2015, at 'Nederlands Trialregister - NTR4997'.
from Cancer via ola Kala on Inoreader http://ift.tt/2rrGkHx
via IFTTT
High lymphatic vessel density and presence of lymphovascular invasion both predict poor prognosis in breast cancer
Abstract
Background
Lymphatic vessel density and lymphovascular invasion are commonly assessed to identify the clinicopathological outcomes in breast cancer. However, the prognostic values of them on patients' survival are still uncertain.
Methods
Databases of PubMed, Embase, and Web of Science were searched from inception up to 30 June 2016. The hazard ratio with its 95% confidence interval was used to determine the prognostic effects of lymphatic vessel density and lymphovascular invasion on disease-free survival and overall survival in breast cancer.
Results
Nineteen studies, involving 4215 participants, were included in this study. With the combination of the results of lymphatic vessel density, the pooled hazard ratios and 95% confidence intervals were 2.02 (1.69–2.40) for disease-free survival and 2.88 (2.07–4.01) for overall survival, respectively. For lymphovascular invasion study, the pooled hazard ratios and 95% confidence intervals were 1.81 (1.57–2.08) for disease-free survival and 1.64 (1.43–1.87) for overall survival, respectively. In addition, 29.56% (827/2798) of participants presented with lymphovascular invasion in total.
Conclusions
Our study demonstrates that lymphatic vessel density and lymphovascular invasion can predict poor prognosis in breast cancer. Standardized assessments of lymphatic vessel density and lymphovascular invasion are needed.
from Cancer via ola Kala on Inoreader http://ift.tt/2rrIYgn
via IFTTT
TUmor-volume to breast-volume RAtio for improving COSmetic results in breast cancer patients (TURACOS); a randomized controlled trial
Abstract
Background
Cosmetic result following breast conserving surgery (BCS) for cancer influences quality of life and psychosocial functioning in breast cancer patients. A preoperative prediction of expected cosmetic result following BCS is not (yet) standard clinical practice and therefore the choice for either mastectomy or BCS is still subjective. Recently, we showed that tumour volume to breast volume ratio as well as tumour location in the breast are independent predictors of superior cosmetic result following BCS. Implementation of a prediction model including both factors, has not been studied in a prospective manner. This study aims to improve cosmetic outcome by implementation of a prediction model in the treatment decision making for breast cancer patients opting for BCS.
Methods/design
Multicentre, single-blinded, randomized controlled trial comparing standard preoperative work-up to a preoperative work-up with addition of the prediction model. Tumour volume to breast volume ratio and tumour location in the breast will be used to predict cosmetic outcome in invasive breast cancer patients opting for BCS. Three dimensional (3D)-ultrasonography will be used to measure the tumour volume to breast volume ratio needed for the prediction model. Sample size was estimated based on a 14% improvement in incidence of superior cosmetic result one year after BCS (71% in the control group versus 85% in the intervention group). Primarily cosmetic outcome will be evaluated by a 6-member independent panel. Secondary endpoints include; (1) patient reported outcome measured by BREAST-Q, EORTC-QLQ-C30/BR23 and EQ-5D-5 L (2) cosmetic outcome as assessed through the BCCT.core software, (3) radiation-induced reaction (4) surgical treatment performed, (5) pathological result and (6) cost-effectiveness. Follow-up data will be collected for 3 years after surgery or finishing radiotherapy.
Discussion
This randomized controlled trial examines the value of a preoperative prediction model for the treatment-decision making. It aims for a superior cosmetic result in breast cancer patients opting for BCS. We expect improvement of patients' quality of life and psychosocial functioning in a cost-effective way.
Trial registration
Prospectively registered, February 17th 2015, at 'Nederlands Trialregister - NTR4997'.
http://ift.tt/2rrGkHx
High lymphatic vessel density and presence of lymphovascular invasion both predict poor prognosis in breast cancer
Abstract
Background
Lymphatic vessel density and lymphovascular invasion are commonly assessed to identify the clinicopathological outcomes in breast cancer. However, the prognostic values of them on patients' survival are still uncertain.
Methods
Databases of PubMed, Embase, and Web of Science were searched from inception up to 30 June 2016. The hazard ratio with its 95% confidence interval was used to determine the prognostic effects of lymphatic vessel density and lymphovascular invasion on disease-free survival and overall survival in breast cancer.
Results
Nineteen studies, involving 4215 participants, were included in this study. With the combination of the results of lymphatic vessel density, the pooled hazard ratios and 95% confidence intervals were 2.02 (1.69–2.40) for disease-free survival and 2.88 (2.07–4.01) for overall survival, respectively. For lymphovascular invasion study, the pooled hazard ratios and 95% confidence intervals were 1.81 (1.57–2.08) for disease-free survival and 1.64 (1.43–1.87) for overall survival, respectively. In addition, 29.56% (827/2798) of participants presented with lymphovascular invasion in total.
Conclusions
Our study demonstrates that lymphatic vessel density and lymphovascular invasion can predict poor prognosis in breast cancer. Standardized assessments of lymphatic vessel density and lymphovascular invasion are needed.
http://ift.tt/2rrIYgn
Onco-testicular sperm extraction (onco-TESE) for bilateral testicular tumors: two case reports
Most patients with testicular cancer are infertile; thus, the preservation of the sperm after surgery is an important factor to consider. We report two cases of bilateral testicular cancer in patients who unde...
http://ift.tt/2rg0yYf
Prospective External Validation of Three Preoperative Risk Scores for Prediction of New Onset Atrial Fibrillation After Cardiac Surgery.
BACKGROUND: Postoperative atrial fibrillation (POAF) is associated with early and late morbidity and mortality of cardiac surgical patients. Prophylactic treatment of atrial fibrillation (AF) has been recommended to improve outcome in cardiac surgical patients at high risk of developing POAF. Reliable models for prediction of POAF are needed to achieve that goal. This study attempted to externally validate 3 risk models proposed for preoperative prediction of POAF in cardiac surgical patients: the POAF score, the CHA2DS2-VASc score, and the Atrial Fibrillation Risk Index. METHODS: This was a prospective cohort study of 1416 adult patients who underwent nonemergent coronary artery bypass graft and/or valve surgery in a single cardiac surgical center between February 2014 and September 2015. A risk score for each of the 3 prediction models was calculated in each patient. All patients were followed for up to 2 weeks, or until hospital discharge, to observe the primary outcome of new onset AF requiring treatment. Discrimination was assessed using receiver operating characteristic curves. Calibration was assessed using the Pearson [chi]2 goodness-of-fit test and calibration plots. Utility of the score to implement AF prophylaxis based on the risk of POAF, in comparison to strategies of treating all patients, or not treating any patients, was assessed via a net benefit analysis. RESULTS: Of the 1416 patients included in this study, 478 had the primary outcome (33.8%). The areas under the receiver operating characteristic curve for prediction of POAF in the population subsets for which the scores were validated were as follows: 0.651 (95% confidence interval [CI], 0.621-0.681) for the POAF score, 0.593 (95% CI, 0.557-0.629) for the CHA2DS2-VASc score (P
http://ift.tt/2rrflf1
http://ift.tt/2rrflf1
Preoperative Warming Versus no Preoperative Warming for Maintenance of Normothermia in Women Receiving Intrathecal Morphine for Cesarean Delivery: A Single Blinded, Randomized Controlled Trial.
BACKGROUND: Rates of hypothermia for women undergoing spinal anesthesia for cesarean delivery are high and prevention is desirable. This trial compared the effectiveness of preoperative warming versus usual care among women receiving intrathecal morphine, which is thought to exacerbate perioperative heat loss. METHODS: A prospective, single-blinded, randomized controlled trial compared 20 minutes of forced air warming (plus intravenous fluid warming) versus no active preoperative warming (plus intravenous fluid warming) in 50 healthy American Society of Anesthesiologists graded II women receiving intrathecal morphine as part of spinal anesthesia for elective cesarean delivery. The primary outcome of maternal temperature change was assessed via aural canal and bladder temperature measurements at regular intervals. Secondary outcomes included maternal thermal comfort, shivering, mean arterial pressure, agreement between aural temperature, and neonatal outcomes (axillary temperature at birth, Apgar scores, breastfeeding, and skin-to-skin contact). The intention-to-treat population was analyzed with descriptive statistics, general linear model analysis, linear mixed-model analysis, [chi]2 test of independence, Mann-Whitney, and Bland-Altman analysis. Full ethical approval was obtained, and the study was registered on the Australia and New Zealand Clinical Trials Registry (Trial No: 367160, registered at http://ift.tt/17L6Qgm). RESULTS: Intention-to-treat analysis (n = 50) revealed no significant difference in aural temperature change from baseline to the end of the procedure between groups: F (1, 47) = 1.2, P = .28. There were no other statistically significant differences between groups in any of the secondary outcomes. CONCLUSIONS: A short period of preoperative warming is not effective in preventing intraoperative temperature decline for women receiving intrathecal morphine. A combination of preoperative and intraoperative warming modalities may be required for this population. (C) 2017 International Anesthesia Research Society
http://ift.tt/2rrwR2V
http://ift.tt/2rrwR2V
Patient Blood Management in Major Orthopedic Surgery: Less Erythropoietin and More Iron?.
Relationship Between a Sepsis Intervention Bundle and In-Hospital Mortality Among Hospitalized Patients: A Retrospective Analysis of Real-World Data.
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Use of the Fluid Challenge in Critically Ill Adult Patients: A Systematic Review.
http://ift.tt/2rryC07
An Etomidate Analogue With Less Adrenocortical Suppression, Stable Hemodynamics, and Improved Behavioral Recovery in Rats.
BACKGROUND: ET-26 hydrochloride (ET-26HCl) is a novel etomidate analogue designed to alleviate the adrenocortical suppression caused by etomidate while retaining the rapid sedative-hypnotic onset and stable hemodynamic features of etomidate. This study compared the anesthetic effect, hemodynamic stability, and recovery profiles of ET-26HCl, etomidate, and the sedative-hypnotic drug propofol in rats. METHODS: The metabolic half-life of ET-26HCl was determined in vitro using high performance liquid chromatography analysis of samples of rat plasma and liver homogenates taken from 3 animals. Hypnotic median effective doses (HD50) of ET-26HCl, etomidate, and propofol were determined by up-and-down methods. Anesthesia effect and mean arterial pressure were estimated using equivalent intravenous (IV) doses of propofol, etomidate, and ET-26HCl in the rats. Serum concentrations of corticosterone were analyzed by enzyme-linked immunosorbent assay. The ability of rats to recover from the sedative-hypnotic effects of the drugs was evaluated using open field and Morris water maze tests at equipotent doses of propofol, etomidate, ET-26HCl, and normal saline. RESULTS: The metabolic half-life of ET-26HCl was 81 +/- 6 minutes in rat plasma and 126 +/- 12 minutes in incubation liver homogenate (mean +/- standard deviation), respectively. In vivo experiments showed that the potency of ET-26HCl to cause a loss of righting reflex in rats was 3 times lower than that of etomidate in the rats. IV propofol caused a greater decrease in mean arterial pressure relative to the baseline (-27.9 mm Hg) than did ET-26HCl (-10.7 mm Hg) and etomidate (-19.4 mm Hg) at equipotent doses. Serum corticosterone levels after drug administration were significantly higher in the ET-26HCl group than in the etomidate group at equivalent doses when measured 15 (P
http://ift.tt/2qtduJE
http://ift.tt/2qtduJE
Cancellation of Elective Cases in a Recently Opened, Tertiary/Quaternary-Level Hospital in the Middle East.
Case cancellations have a negative financial impact due to revenue loss and the potential costs of underutilized time. The goals of this study at a recently opened hospital in the Middle East were to measure the cancellation rates for elective surgical or endoscopic cases and to identify the reasons for cancellation. During the 1-month study period, 170 (22.4%) of the 760 scheduled cases were cancelled. Cultural norms and patient no-shows on the day of surgery accounted for the majority of case cancellations. Understanding local factors on hospital functions may be vital for organizations expanding into new geographic areas. (C) 2017 International Anesthesia Research Society
http://ift.tt/2rrcjHC
http://ift.tt/2rrcjHC
Cerebral Oxygen Saturation in Children With Congenital Heart Disease and Chronic Hypoxemia.
BACKGROUND: Increased hemoglobin (Hb) concentration accompanying hypoxemia is a compensatory response to maintain tissue oxygen delivery. Near infrared spectroscopy (NIRS) is used clinically to detect abnormalities in the balance of cerebral tissue oxygen delivery and consumption, including in children with congenital heart disease (CHD). Although NIRS-measured cerebral tissue O2 saturation (ScO2) correlates with arterial oxygen saturation (SaO2), jugular bulb O2 saturation (SjbO2), and Hb, little data exist on the interplay between these factors and cerebral O2 extraction (COE). This study investigated the associations of ScO2 and [DELTA]SaO2-ScO2 with SaO2 and Hb and verified the normal range of ScO2 in children with CHD. METHODS: Children undergoing cardiac catheterization for CHD were enrolled in a calibration and validation study of the FORE-SIGHT NIRS monitor. Two pairs of simultaneous arterial and jugular bulb samples were drawn for co-oximetry, calculation of a reference ScO2 (REF CX), and estimation of COE. Pearson correlation and linear regression were used to determine relationships between O2 saturation parameters and Hb. Data were also analyzed according to diagnostic group defined as acyanotic (SaO2 >= 90%) and cyanotic (SaO2
http://ift.tt/2qt8RPu
http://ift.tt/2qt8RPu
Strategies for Management of Relapsed or Refractory Hodgkin Lymphoma
The advent of effective therapies has improved outcomes for those with newly diagnosed Hodgkin lymphoma (HL), with a resulting cure rate of at least 80%. However, with limited data on therapeutic options in the setting of advanced disease, individualized treatment is recommended, and potential long-term effects of therapy remain a key consideration. At the NCCN 22nd Annual Conference, Dr. Leo I. Gordon explored strategies for systemic therapy in the relapsed or refractory setting, focusing primarily on the standard of high-dose therapy/autologous stem cell rescue, the CD30-targeted antibody drug conjugate brentuximab vedotin, and checkpoint inhibition.
http://ift.tt/2pX0oQS
Life After Treatment: Quality-of-Life Concerns in Patients Treated for Cancer
Traditionally, the physical, psychological, and psychosocial long-term needs of cancer survivors have received little attention compared with screening for cancer recurrence and secondary cancers. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Survivorship offer recommendations for various survivorship concerns, and those for improving menopausal symptoms were presented at the NCCN 22nd Annual Conference. Key considerations in managing menopausal symptoms in cancer survivors were reviewed, with chemotherapy-induced amenorrhea, fertility concerns, and both hormonal and nonhormonal therapeutic options featured.
http://ift.tt/2pWPafm
NCCN Roundtable Tackles Disparities in Cancer Care
During a roundtable on disparities in cancer care at the recent NCCN 22nd Annual Conference: Improving the Quality, Effectiveness, and Efficiency of Cancer Care, panelists from a variety of disciplines brought professional and personal experiences to the discussion of eliminating cancer disparities and reducing differences in incidence and mortality rates among minority populations. The panel agreed that these issues must be addressed through research in prevention, screening, clinical trials, and equal access to quality care.
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Minimally Invasive Techniques for Treating Gynecologic Malignancies
For many women with endometrial and cervical cancers, minimally invasive surgery represents an alternative standard of care to open abdominal procedures, with fewer complications, better postoperative quality of life, and overall lower cost. At the NCCN 22nd Annual Conference, Amanda N. Fader, MD, reviewed several minimally invasive strategies for treating gynecologic cancers, including conventional laparoscopy, robotic-assisted laparoscopy, sentinel lymph node technology, and single-port surgery; highlighted some of the contemporary literature on the role of these procedures; and explored some of the challenges and barriers to their successful performance.
http://ift.tt/2pWPniD
Use of Biomarkers and Multigene Assays in Breast Cancer
All patients with early breast cancer should be classified by subgroup through testing estrogen receptor, progesterone receptor, and HER2 status, with or without Ki-67 proliferation percentage. Genomic expression profiling aids clinical decision-making in most patients, because most are estrogen receptor–positive. The commercially available classifiers are prognostic for distant recurrence in node-negative and also node-positive patients. Patients at genomically low risk have excellent 5-year outcomes with endocrine therapy alone. Some assays also predict for benefit from adjuvant endocrine therapy and chemotherapy in node-negative and node-positive patients, but with varying levels of evidence. Genomic classifiers are also prognostic of late relapse and may predict benefit from extended adjuvant endocrine therapy.
http://ift.tt/2qshdqv
New Treatment Options for the Management of Multiple Myeloma
Multiple myeloma (MM) is a complex disease characterized by considerable genetic heterogeneity. The updated NCCN Guidelines for MM have added new "preferred" regimens for transplant and nontransplant candidates, and have moved some formerly "preferred" regimens to the "other" category. Supportive care has improved outcomes for patients, and new treatments in combination have extended survival for patients with MM. Novel agents on the horizon are poised to raise the bar even further.
http://ift.tt/2pX1Bra
New Approaches to Endocrine Therapy for Breast Cancer
The management of advanced hormone receptor–positive disease has evolved with the emergence of CDK4/6 inhibitors. Improvements in progression-free survival of approximately 10 months were noted in pivotal trials of palbociclib. Strong efficacy was also seen with ribociclib, which was recently approved by the FDA. In the adjuvant treatment setting of hormone receptor–positive disease, an important issue for consideration is the duration of endocrine therapy.
http://ift.tt/2qs7oZC
Active Systemic Treatment of Pancreatic Cancer
By 2020, pancreatic cancer is expected to be the second most common cause of cancer-related death, exceeded only by lung cancer. During her presentation at the NCCN 22nd Annual Conference, Dr. Margaret Tempero offered an update on the current state of systemic treatment of pancreatic cancer, focusing on resectable/borderline resectable, locally advanced, and metastatic disease.
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NCCN Guidelines Update: Evolving Radiation Therapy Recommendations for Breast Cancer
In the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer, among adjuvant radiotherapy options for whole-breast irradiation after breast-conserving surgery, hypofractionation is preferred. For the use of accelerated partial-breast irradiation, the NCCN Guidelines have adopted the updated definition of "suitability" used by the American Society for Radiation Oncology. Regional nodal irradiation is indicated—either in the setting of breast-conserving surgery or after mastectomy—for women with ≥4 positive nodes and should be strongly considered for 1 to 3 positive lymph nodes and select patients with node-negative disease deemed at high risk for recurrence.
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Novel Treatment Options for Neuroendocrine Tumors
Neuroendocrine tumors (NETs) are not as rare as once thought, with a current prevalence that is estimated to be higher than that of many other gastrointestinal tumors. Multiple treatment options are available for these tumors, which are categorized according to their histology and site of origin. For patients with metastatic disease, somatostatin analogues are often the initial treatment, with other options considered when these drugs fail.
http://ift.tt/2pWPhr5
What, When, and How of Biomarker Testing in Non-Small Cell Lung Cancer
Biomarker testing is recommended for all patients diagnosed with non–small cell lung cancer. At a minimum, testing should include the mutations/fusions EGFR, ALK, ROS1, and the protein programmed death ligand-1 (PD-L1), because FDA-approved therapies are available for these alterations. Other actionable molecular findings include RET rearrangements, BRAFV600E mutations, and MET exon 14 alterations. If adequate testing was not performed at treatment initiation, molecular testing should be performed before administration of subsequent lines of therapy. In patients with EGFR-mutant lung cancer, when resistance develops, physicians should seek to identify the T790M mutation using plasma and tissue assays, because osimertinib therapy is available for this mutation.
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Biomarker-Based Treatment Selection in Non-Small Cell Lung Cancer
Patients with non–small cell lung cancer must be tested for biomarkers. Currently, treatments directed against EGFR, ALK, and ROS1 mutations are standard of care. A number of emerging new targets and treatments are on the horizon.
http://ift.tt/2qs1UOA
Chronic Lymphocytic Leukemia: Individualizing Treatment Approach
A host of new therapies are now available for treating patients with chronic lymphocytic leukemia (CLL) in both the upfront and relapsed or refractory settings. Although the optimal use of these agents is still being defined, established and emerging prognostic markers aid in the selection of appropriate treatment with the best chance of success. At the NCCN 22nd Annual Conference, Dr. Andrew Zelenetz discussed the role of the CLL-International Prognostic Index for risk stratification, reviewed optimal first-line therapy options, and then presented updated clinical trial data on the novel agents being used in the relapsed or refractory setting. The hope is that chronic therapy will be replaced by combinations that provide high rates of minimal residual disease negativity with durable remissions.
http://ift.tt/2pWZkwk
Immunotherapies for Lung Cancer
In 2017, immunotherapy is the standard of care for patients with non–small cell lung cancer (NSCLC) either in the first or second line depending on programmed death ligand-1 (PD-L1) and mutation status. For first-line therapy, pembrolizumab is currently the standard of care for patients whose tumors express PD-L1 >50%. All patients with NSCLC should undergo PD-L1 testing before initiating treatment on pembrolizumab. For patients not eligible in the first line, immunotherapy is the standard of care for most in the second line. Nivolumab and atezolizumab are approved in all patients as second-line therapies after platinum-based doublet failure regardless PD-L1 expression level, although pembrolizumab is approved as second-line therapy for those whose tumors express PD-L1 >1%.
http://ift.tt/2pX0rfn
NCCN Debuts New Guidelines for Myeloproliferative Neoplasms
For the first time, NCCN has published guidelines specifically geared toward treating myeloproliferative neoplasms (MPNs). The first set of guidelines was developed for myelofibrosis (MF), and was presented at the NCCN 22nd Annual Conference. Future guidelines will be issued for polycythemia vera, essential thrombocytopenia, and atypical MPNs. Patients with MF can have an unpredictable course, one that is largely dependent on the presence of certain molecular alterations. Models are currently emerging that take into account molecular factors. Only one drug is currently approved for MF, the oral JAK1/2 inhibitor ruxolitinib, which has been shown to significantly reduce splenomegaly and improve symptoms.
http://ift.tt/2qrUJWs
Keynote Address: When Breath Becomes Air--As Physician Becomes Patient
As part of the NCCN 22nd Annual Conference: Improving the Quality, Effectiveness, and Efficiency of Cancer Care, Lucy Kalanithi, MD, wife of now-deceased best-selling author Paul Kalanithi (When Breath Becomes Air), and Heather Wakelee, MD, Paul's oncologist, discussed—for the first time together in a public forum—Paul's experience of going from a neurosurgery resident to a patient with cancer with a terminal diagnosis. Robert Carlson, MD, moderated the discussion.
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Opportunities and Challenges: Human Papillomavirus and Cancer
Mucosal exposure to human papillomavirus (HPV) can lead to anogenital and head and neck (H&N) cancer. Vaccination at a young age can be almost 100% effective in preventing HPV infection with the viral subtypes in both men and women, at least for disease in the anogenital tract. Therapeutic strategies targeting HPV in cervical dysplasia and cancer are showing promise as well in regressing dysplasia and controlling disease. That HPV-positive H&N cancer is a different disease from HPV-negative disease, with different molecular and clinical features and prognosis, is becoming better appreciated. At this time, however, the NCCN Guidelines for H&N Cancers do not distinguish between the types. This is expected to change.
http://ift.tt/2qs1k34
Systemic Management of Colorectal Cancer
Advances have been made in the systemic treatment of colorectal cancer, with approximately 12 chemotherapy or biologic agents approved for use as a single agent or in a combination. However, numerous gaps in our understanding of the disease remain, such as the lack of benefit with biologics in the adjuvant setting, the absence of biomarkers for most systemic therapies, and the reason why left-sided and right-sided tumors behave differently. At the 22nd NCCN Annual Conference, Dr. Wells A. Messersmith presented several impactful updates to the 2017 NCCN Clinical Practice Guidelines in Oncology for Colon Cancer and reviewed the outcomes with a host of therapies used for both early-stage and metastatic disease.
http://ift.tt/2pXbfdo
ACTH-secreting medullary thyroid cancer: a case series
Summary
Medullary thyroid cancer (MTC) is a rare neuroendocrine tumour that originates from the parafollicular cells of the thyroid gland. The most common presentation of MTC is with a single nodule; however, by the time of diagnosis, most have spread to the surrounding cervical lymph nodes. Cushing's syndrome is a rare complication of MTC and is due to ectopic adrenocorticotrophic hormone (ACTH) secretion by tumour cells. Cushing's syndrome presents a challenging diagnostic and management issue in patients with MTC. Tyrosine kinase inhibitors (TKI) previously used for the management of metastatic MTC have become an important therapeutic option for the management of ectopic ACTH in metastatic MTC. The article describes three cases of ectopic ACTH secretion in MTC and addresses the significant diagnostic and management challenges related to Cushing's syndrome in metastatic MTC.
Learning points:Medullary thyroid cancer (MTC) is a rare neuroendocrine tumour.
Cushing's syndrome is a rare complication of MTC that has a significant impact on patients' morbidity and mortality.
Tyrosine kinase inhibitors (TKI) provide an important therapeutic option for the management of ectopic ACTH in metastatic MTC.
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Locoregional therapy with α-emitting trastuzumab against peritoneal metastasis of HER2-positive gastric cancer in mice
Abstract
Peritoneal metastasis of gastric cancer (PMGC) is incurable and thus has an extremely poor prognosis. We have found however that locoregionally administered trastuzumab armed with a radionuclide astatine-211 (211At)-emitting α-particle (211At-trastuzumab) is effective against HER2-positive PMGC in a xenograft mouse model. We first observed that 211At-trastuzumab can specifically bind and effectively kill NCI-N87 (N87) cells, which are HER2-positive human metastatic GC cells, both in vitro and in subcutaneous tumors. We established a PMGC mouse model using N87 xenografts stably expressing luciferase to test α-particle radioimmunotherapy with 211At-trastuzumab against PMGC. Biodistribution analysis in this PMGC mouse model revealed that the intraperitoneal administration of 211At-trastuzumab (1 MBq) was a more efficient means of delivery of 211At into metastatic tumors than intravenous injection; the maximum tumor uptake with intraperitoneal administration was over 60 percent injected dose per gram (%ID/g) compared to about 18%ID/g with intravenous injection. Surprisingly, a single intraperitoneal injection of 211At-trastuzumab (1 MBq) was sufficient to completely eradicate intraperitoneally disseminated HER2-positive GC xenografts in two of six treated mice by inducing DNA double-strand breaks, and to drastically reduce the tumor burden in three further mice. No body weight loss, leukocytopenia or significant biochemical changes in liver and kidney function were observed in the treatment group. Accordingly, locoregionally administered 211At-trastuzumab significantly prolonged the survival time of HER2-positive PMGC mice compared with control treatments. Our results provide a proof-of-concept demonstration that locoregional therapy with 211At-trastuzumab may offer a new treatment option for HER2-positive PMGC.
This article is protected by copyright. All rights reserved.
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Small bowel obstruction due to ingestion of rubber balls
Abstract
We report a case of a 10-month-old girl who presented with a 10-day history of emesis that became bilious on the last day. The initial evaluation suggested small bowel obstruction. An upper gastrointestinal study confirmed the normal location of the duodenojejunal junction with normal rotation and no evidence of midgut volvulus. Ultrasound (US) evaluation demonstrated two intraluminal lesions that do not follow the typical features of solid or cystic lesions. Two rubber balls were found at surgery to be responsible for the small bowel obstruction. Foreign body ingestion is common in children, but this case demonstrates a unusual foreign object to be ingested as well as the US appearance of this particular foreign body.
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