This work explores how the choice of prescription isodose line (IDL) affects the dose gradient, target coverage, and treatment time for Gamma Knife radiosurgery when a smaller shot is encompassed within a larg...
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Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Παρασκευή 24 Νοεμβρίου 2017
Optimization of the prescription isodose line for Gamma Knife radiosurgery using the shot within shot technique
Optimization of the prescription isodose line for Gamma Knife radiosurgery using the shot within shot technique
This work explores how the choice of prescription isodose line (IDL) affects the dose gradient, target coverage, and treatment time for Gamma Knife radiosurgery when a smaller shot is encompassed within a larg...
http://ift.tt/2zB7tjI
A randomised phase II study of chemoradiotherapy with or without nimotuzumab in locally advanced oesophageal cancer: NICE trial
Source:European Journal of Cancer, Volume 88
Author(s): Gilberto de Castro Junior, José Getúlio Segalla, Sérgio Jobim de Azevedo, Carlos José Andrade, Daniel Grabarz, Bruno de Araújo Lima França, Auro Del Giglio, Nicolas Silva Lazaretti, Maria Nunes Álvares, José Luiz Pedrini, Celio Kussumoto, João Nunes de Matos Neto, Nora Manoukian Forones, Hezio Jadir Fernandes Júnior, Giuliano Borges, Gustavo Girotto, Ismael Dale Cotrim Guerreiro da Silva, Fauze Maluf-Filho, Nils Gunnar Skare
PurposeChemoradiotherapy is the standard treatment for patients with inoperable locally advanced oesophageal cancer. We sought to assess the safety and efficacy of chemoradiation combined with nimotuzumab, a humanised antibody directed against epidermal growth factor receptor (EGFR).Patients and methodsUntreated patients with inoperable locally advanced oesophageal cancer and no distant metastases were randomised to chemoradiotherapy (cisplatin and fluorouracil combined with external beam radiation) alone or in combination with nimotuzumab. The primary end-point was the endoscopic complete response (eCR) rate, and secondary end-points comprised quality of life (QoL) and safety. The combined eCR and pathologic complete response (cEPCR) and overall survival (OS) were also evaluated.ResultsWe enrolled 107 patients with a mean age of 59 years, and 93% had squamous cell carcinoma. Toxicity was manageable in both arms with no important differences in adverse events (AEs). We performed post-treatment endoscopies in 67 patients, including 60 who had a biopsy. In the intent-to-treat population, the eCR rates with and without nimotuzumab were 47.2% and 33.3% (P = 0.17), respectively, and the cEPCR rates were 62.3% and 37.0% (P = 0.02), respectively. With a median follow-up of 14.7 months, the hazard ratio (HR) for OS was 0.68 (95% confidence interval (CI): 0.44–1.07; P = 0.09) with a median OS of 15.9 months for the nimotuzumab arm and 11.5 months for the control arm. Regarding QoL, a significant difference was observed for the physical subscale score (P = 0.03) with lower values for the control arm.ConclusionCombined chemoradiotherapy plus nimotuzumab is safe for patients with locally advanced oesophageal cancer, it appears to increase the cEPCR rate, and without compromising QoL.Clinical trialsIdentification number: EF024-201; Trial registry: NCT01249352.
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Farewell to monomodality treatment in patients with WHO lower grade glioma?
Source:European Journal of Cancer
Author(s): Emilie Le Rhun, Thierry Gorlia
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Diagnostic accuracy of coronary opacification derived from coronary computed tomography angiography to detect ischemia: first validation versus single-photon emission computed tomography
Abstract
Background
Estimation of functional relevance of a coronary stenosis by fractional flow reserve (FFR) from coronary computed tomography angiography (CCTA) has recently provided encouraging results. Due to its limited availability, the corrected contrast opacification (CCO) decrease and the transluminal attenuation gradient (TAG) were suggested as less complex alternatives. The aim of the present study was to assess the accuracy of CCO decrease and TAG to predict ischemia as assessed by single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI).
Results
This retrospective study included 72 patients who underwent hybrid CCTA/SPECT MPI with at least one coronary artery stenosis. Of 127 vessels with a coronary stenosis in CCTA, 38 (30%) were causing ischemia in its subtending myocardium. The area under the curve (AUC) for CCO decrease to predict ischemia was 0.707 with sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of 74, 64, 85, 47, and 67%, respectively. For TAG, the AUC was 0.469.
Conclusions
CCTA-derived CCO decrease but not TAG predicts ischemia in SPECT MPI. The negative predictive value of CCO decrease of 85% may confer clinical implications in the diagnostic work-up of patients with a coronary stenosis.
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Evaluation of the novel TSPO radiotracer [ 18 F] VUIIS1008 in a preclinical model of cerebral ischemia in rats
Abstract
Background
In vivo positron-emission tomography (PET) imaging of transporter protein (TSPO) expression is an attractive and indispensable tool for the diagnosis and therapy evaluation of neuroinflammation after cerebral ischemia. Despite several radiotracers have shown an excellent capacity to image neuroinflammation, novel radiotracers such as [18F] VUIIS1008 have shown promising properties to visualize and quantify the in vivo expression of TSPO.
Methods
Longitudinal in vivo magnetic resonance (MRI) and PET imaging studies with the novel TSPO radiotracer 2-(5,7-diethyl-2-(4-(2-[18F] fluoroethoxy) phenyl) pyrazolo [1,5-a] pyrimidin-3-yl)-N, N-diethylacetamide ([18F] VUIIS1008), and (N, N-diethyl-2-(2-[4-(2-fluoroethoxy)-phenyl]-5,7-dimethyl-pyrazolo [1,5-a] yrimidin-3-yl)-acetamide ([18F] DPA-714) were carried out before and at days 1, 3, 7, 14, 21, and 28 following the transient middle cerebral artery occlusion (MCAO) in rats.
Results
MRI images showed the extension and evolution of the brain infarction after ischemic stroke in rats. PET imaging with [18F] VUIIS1008 and [18F] DPA714 showed a progressive increase in the ischemic brain hemisphere during the first week, peaking at day 7 and followed by a decline from days 14 to 28 after cerebral ischemia. [18F] DPA714 uptake showed a mild uptake increase compared to [18F] VUIIS1008 in TSPO-rich ischemic brain regions. In vivo [18F] VUIIS1008 binding displacement with VUIIS1008 was more efficient than DPA714. Finally, immunohistochemistry confirmed a high expression of TSPO in microglial cells at day 7 after the MCAO in rats.
Conclusions
Altogether, these results suggest that [18F] VUIIS1008 could become a valuable tool for the diagnosis and treatment evaluation of neuroinflammation following ischemic stroke.
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Diagnostic accuracy of coronary opacification derived from coronary computed tomography angiography to detect ischemia: first validation versus single-photon emission computed tomography
Abstract
Background
Estimation of functional relevance of a coronary stenosis by fractional flow reserve (FFR) from coronary computed tomography angiography (CCTA) has recently provided encouraging results. Due to its limited availability, the corrected contrast opacification (CCO) decrease and the transluminal attenuation gradient (TAG) were suggested as less complex alternatives. The aim of the present study was to assess the accuracy of CCO decrease and TAG to predict ischemia as assessed by single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI).
Results
This retrospective study included 72 patients who underwent hybrid CCTA/SPECT MPI with at least one coronary artery stenosis. Of 127 vessels with a coronary stenosis in CCTA, 38 (30%) were causing ischemia in its subtending myocardium. The area under the curve (AUC) for CCO decrease to predict ischemia was 0.707 with sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of 74, 64, 85, 47, and 67%, respectively. For TAG, the AUC was 0.469.
Conclusions
CCTA-derived CCO decrease but not TAG predicts ischemia in SPECT MPI. The negative predictive value of CCO decrease of 85% may confer clinical implications in the diagnostic work-up of patients with a coronary stenosis.
http://ift.tt/2i4JPop
Evaluation of the novel TSPO radiotracer [ 18 F] VUIIS1008 in a preclinical model of cerebral ischemia in rats
Abstract
Background
In vivo positron-emission tomography (PET) imaging of transporter protein (TSPO) expression is an attractive and indispensable tool for the diagnosis and therapy evaluation of neuroinflammation after cerebral ischemia. Despite several radiotracers have shown an excellent capacity to image neuroinflammation, novel radiotracers such as [18F] VUIIS1008 have shown promising properties to visualize and quantify the in vivo expression of TSPO.
Methods
Longitudinal in vivo magnetic resonance (MRI) and PET imaging studies with the novel TSPO radiotracer 2-(5,7-diethyl-2-(4-(2-[18F] fluoroethoxy) phenyl) pyrazolo [1,5-a] pyrimidin-3-yl)-N, N-diethylacetamide ([18F] VUIIS1008), and (N, N-diethyl-2-(2-[4-(2-fluoroethoxy)-phenyl]-5,7-dimethyl-pyrazolo [1,5-a] yrimidin-3-yl)-acetamide ([18F] DPA-714) were carried out before and at days 1, 3, 7, 14, 21, and 28 following the transient middle cerebral artery occlusion (MCAO) in rats.
Results
MRI images showed the extension and evolution of the brain infarction after ischemic stroke in rats. PET imaging with [18F] VUIIS1008 and [18F] DPA714 showed a progressive increase in the ischemic brain hemisphere during the first week, peaking at day 7 and followed by a decline from days 14 to 28 after cerebral ischemia. [18F] DPA714 uptake showed a mild uptake increase compared to [18F] VUIIS1008 in TSPO-rich ischemic brain regions. In vivo [18F] VUIIS1008 binding displacement with VUIIS1008 was more efficient than DPA714. Finally, immunohistochemistry confirmed a high expression of TSPO in microglial cells at day 7 after the MCAO in rats.
Conclusions
Altogether, these results suggest that [18F] VUIIS1008 could become a valuable tool for the diagnosis and treatment evaluation of neuroinflammation following ischemic stroke.
http://ift.tt/2jYrGck
Malignant acanthosis nigricans: an early diagnostic clue for gastric adenocarcinoma
Abstract
Background
Malignant acanthosis nigricans (MAN), characterized by the presence of a hyperpigmented, velvety cutaneous thickening, is recognized as a cutaneous sign of internal malignancy. Few MAN has been reported in the Asian race ever before.
Case presentation
Here, we report a rare case of MAN with severe mucosa and soles and extraordinary facial involvement in the Asian race. A 74-year-old man presented with hyperkeratotic eruption for 7 months. Physical examination revealed hyperkeratotic plaques on the face, dorsal skin of fingers and heels, and papillomatosis of buccal mucosa. Biopsy findings from skin lesion revealed hyperkeratosis, papillomatosis, and hyperpigmentation of the basal layer. The endoscopic ultrasound with biopsy of the gastric tissue revealed gastric cardia tubular adenocarcinoma. The patient was diagnosed with MAN associated with gastric adenocarcinoma, immediately following tumor resection and lymphadenectomy. A slight improvement was seen in the skin condition but died of cancer cachexia 3 months later.
Conclusions
We report our typical patient to highlight the importance of MAN, which was an early clue to the discovery of gastric adenocarcinoma.
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Malignant acanthosis nigricans: an early diagnostic clue for gastric adenocarcinoma
Abstract
Background
Malignant acanthosis nigricans (MAN), characterized by the presence of a hyperpigmented, velvety cutaneous thickening, is recognized as a cutaneous sign of internal malignancy. Few MAN has been reported in the Asian race ever before.
Case presentation
Here, we report a rare case of MAN with severe mucosa and soles and extraordinary facial involvement in the Asian race. A 74-year-old man presented with hyperkeratotic eruption for 7 months. Physical examination revealed hyperkeratotic plaques on the face, dorsal skin of fingers and heels, and papillomatosis of buccal mucosa. Biopsy findings from skin lesion revealed hyperkeratosis, papillomatosis, and hyperpigmentation of the basal layer. The endoscopic ultrasound with biopsy of the gastric tissue revealed gastric cardia tubular adenocarcinoma. The patient was diagnosed with MAN associated with gastric adenocarcinoma, immediately following tumor resection and lymphadenectomy. A slight improvement was seen in the skin condition but died of cancer cachexia 3 months later.
Conclusions
We report our typical patient to highlight the importance of MAN, which was an early clue to the discovery of gastric adenocarcinoma.
http://ift.tt/2iPldNj
PRDM14 directly interacts with heat shock proteins HSP90α and GRP78
Abstract
PRDM14 is overexpressed in various cancers and can regulate cancer phenotype under certain conditions. Inhibiting PRDM14 expression in breast and pancreatic cancers has been reported to reduce cancer stem-like phenotypes, which are associated with aggressive tumor properties. Therefore, PRDM14 is considered a promising target for cancer therapy. To develop a pharmaceutical treatment, the mechanism and interacting partners of PRDM14 needs to be clarified. Here, we identified the proteins interacting with PRDM14 in triple-negative breast cancer cells (TNBCs), which do not express the three most common types of receptors (estrogen receptors, progesterone receptors, and HER2). We obtained thirteen candidates that were pulled down with PRDM14 in TNBC HCC1937 and identified them by mass spectrometry. Two candidates - glucose-regulated protein 78 (GRP78) and heat shock protein 90-α (HSP90α) – were confirmed in immunoprecipitation assay in two TNBC cell lines (HCC1937 and MDA-MB231). Surface plasmon resonance (SPR) analysis using GST-PRDM14 revealed that these two proteins directly interacted with PRDM14 and that the interactions required the C-terminal region of PRDM14, which includes zinc finger motifs. We also confirmed the interactions in living cells by NanoLuc luciferase-based bioluminescence resonance energy transfer (NanoBRET) assay. Moreover, HSP90 inhibitors (17DMAG and HSP990) significantly decreased breast cancer stem-like CD24-CD44+ and side population (SP) cells in HCC1937 cells, but not in PRDM14 knockdown HCC1937 cells. The combination of the GRP78 inhibitor HA15 and PRDM14 knockdown significantly decreased cell proliferation and SP cell number in HCC1937 cells. These results suggested HSP90α and GRP78 interact with PRDM14 and participate in cancer regulation.
This article is protected by copyright. All rights reserved.
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PRDM14 directly interacts with heat shock proteins HSP90α and GRP78
Abstract
PRDM14 is overexpressed in various cancers and can regulate cancer phenotype under certain conditions. Inhibiting PRDM14 expression in breast and pancreatic cancers has been reported to reduce cancer stem-like phenotypes, which are associated with aggressive tumor properties. Therefore, PRDM14 is considered a promising target for cancer therapy. To develop a pharmaceutical treatment, the mechanism and interacting partners of PRDM14 needs to be clarified. Here, we identified the proteins interacting with PRDM14 in triple-negative breast cancer cells (TNBCs), which do not express the three most common types of receptors (estrogen receptors, progesterone receptors, and HER2). We obtained thirteen candidates that were pulled down with PRDM14 in TNBC HCC1937 and identified them by mass spectrometry. Two candidates - glucose-regulated protein 78 (GRP78) and heat shock protein 90-α (HSP90α) – were confirmed in immunoprecipitation assay in two TNBC cell lines (HCC1937 and MDA-MB231). Surface plasmon resonance (SPR) analysis using GST-PRDM14 revealed that these two proteins directly interacted with PRDM14 and that the interactions required the C-terminal region of PRDM14, which includes zinc finger motifs. We also confirmed the interactions in living cells by NanoLuc luciferase-based bioluminescence resonance energy transfer (NanoBRET) assay. Moreover, HSP90 inhibitors (17DMAG and HSP990) significantly decreased breast cancer stem-like CD24-CD44+ and side population (SP) cells in HCC1937 cells, but not in PRDM14 knockdown HCC1937 cells. The combination of the GRP78 inhibitor HA15 and PRDM14 knockdown significantly decreased cell proliferation and SP cell number in HCC1937 cells. These results suggested HSP90α and GRP78 interact with PRDM14 and participate in cancer regulation.
This article is protected by copyright. All rights reserved.
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Childhood cancer incidence and survival in Japan and England: A population-based study (1993-2010)
Abstract
This study aimed to compare cancer incidence and trends in survival for children diagnosed in Japan and England, using population-based cancer registry data. The analysis was based on 5,192 children with cancer (age 0-14 years) from six prefectural cancer registries in Japan and 21,295 children diagnosed in England during 1993-2010. Differences in incidence rates between the two countries were measured with Poisson regression models. Overall survival was estimated using the Kaplan-Meier method. Incidence rates for Hodgkin lymphoma, renal tumours, and Ewing sarcomas in England were more than twice as high as those in Japan. Incidence of germ cell tumours, hepatic tumours, neuroblastoma, and acute myeloid leukaemia (AML) was higher in Japan than in England. Incidence of all cancers combined decreased in Japan throughout the period 1993 to 2010, which was mainly explained by a decrease in registration of neuroblastoma in infants. For many cancers, 5-year survival improved in both countries. The improvement in survival in chronic myeloid leukaemia (CML) was particularly dramatic in both countries. However, 5-year survival remained less than 80% in 2005-2008 in both countries for AML, brain tumours, soft tissue sarcomas, malignant bone tumours, and neuroblastoma (age 1-14 years). There were significant differences in incidence of several cancers between countries, suggesting variation in genetic susceptibility and possibly environmental factors. The decrease in incidence for all cancers combined in Japan was related to the cessation of the national screening programme for neuroblastoma. The large improvement in survival from CML coincided with the introduction of effective therapy (imatinib).
This article is protected by copyright. All rights reserved.
http://ift.tt/2AaAsIh
Childhood cancer incidence and survival in Japan and England: A population-based study (1993-2010)
Abstract
This study aimed to compare cancer incidence and trends in survival for children diagnosed in Japan and England, using population-based cancer registry data. The analysis was based on 5,192 children with cancer (age 0-14 years) from six prefectural cancer registries in Japan and 21,295 children diagnosed in England during 1993-2010. Differences in incidence rates between the two countries were measured with Poisson regression models. Overall survival was estimated using the Kaplan-Meier method. Incidence rates for Hodgkin lymphoma, renal tumours, and Ewing sarcomas in England were more than twice as high as those in Japan. Incidence of germ cell tumours, hepatic tumours, neuroblastoma, and acute myeloid leukaemia (AML) was higher in Japan than in England. Incidence of all cancers combined decreased in Japan throughout the period 1993 to 2010, which was mainly explained by a decrease in registration of neuroblastoma in infants. For many cancers, 5-year survival improved in both countries. The improvement in survival in chronic myeloid leukaemia (CML) was particularly dramatic in both countries. However, 5-year survival remained less than 80% in 2005-2008 in both countries for AML, brain tumours, soft tissue sarcomas, malignant bone tumours, and neuroblastoma (age 1-14 years). There were significant differences in incidence of several cancers between countries, suggesting variation in genetic susceptibility and possibly environmental factors. The decrease in incidence for all cancers combined in Japan was related to the cessation of the national screening programme for neuroblastoma. The large improvement in survival from CML coincided with the introduction of effective therapy (imatinib).
This article is protected by copyright. All rights reserved.
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Delineation of the primary tumour Clinical Target Volumes (CTV-P) in laryngeal, hypopharyngeal, oropharyngeal and oral cavity squamous cell carcinoma: AIRO, CACA, DAHANCA, EORTC, GEORCC, GORTEC, HKNPCSG, HNCIG, IAG-KHT, LPRHHT, NCIC CTG, NCRI, NRG Oncology, PHNS, SBRT, SOMERA, SRO, SSHNO, TROG consensus guidelines
Few studies have reported large inter-observer variations in target volume selection and delineation in patients treated with radiotherapy for head and neck squamous cell carcinoma. Consensus guidelines have been published for the neck nodes (see Grégoire et al., 2003, 2014), but such recommendations are lacking for primary tumour delineation. For the latter, two main schools of thoughts are prevailing, one based on geometric expansion of the Gross Tumour Volume (GTV) as promoted by DAHANCA, and the other one based on anatomical expansion of the GTV using compartmentalization of head and neck anatomy.
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Low Arid1a Expression Correlates with Poor Prognosis and Promotes Cell Proliferation and Metastasis in Osteosarcoma
Abstract
AT-rich interactive domain-containing protein 1A (ARID1A) has been shown to function as a tumour suppressor in various malignancies. However, the biological role of ARID1A in osteosarcoma is not clear. The present study aimed to investigate the expression pattern, prognostic value and the biological role of ARID1A in human osteosarcoma. ARID1A expression in 53 osteosarcoma surgical specimens was examined by quantitative real-time polymerase chain reaction, and its clinical significance was analysed. The role of ARID1A in cell proliferation, apoptosis, and metastasis were examined. ARID1A mRNA expression were significantly down-regulated in osteosarcoma tumours from that in matched adjacent non-tumour tissues. ARID1A expression was significantly inversely correlated with tumour stage and distant metastasis, as well as poor overall survival in patients with osteosarcoma. Furthermore, ARID1A mRNA was down-regulated in four human osteosarcoma cell lines MG-63, U2OS, HOS and Saos-2. Restoring of ARID1A expression in MG-63 and U2OS cells significantly inhibited cell proliferation and metastasis in vitro. Collectively, our data demonstrate that ARID1A may serve as a tumour suppressor in osteosarcoma progression, and represent a valuable prognostic marker and potential therapeutic target for osteosarcoma.
http://ift.tt/2A36B6C
Low Arid1a Expression Correlates with Poor Prognosis and Promotes Cell Proliferation and Metastasis in Osteosarcoma
Abstract
AT-rich interactive domain-containing protein 1A (ARID1A) has been shown to function as a tumour suppressor in various malignancies. However, the biological role of ARID1A in osteosarcoma is not clear. The present study aimed to investigate the expression pattern, prognostic value and the biological role of ARID1A in human osteosarcoma. ARID1A expression in 53 osteosarcoma surgical specimens was examined by quantitative real-time polymerase chain reaction, and its clinical significance was analysed. The role of ARID1A in cell proliferation, apoptosis, and metastasis were examined. ARID1A mRNA expression were significantly down-regulated in osteosarcoma tumours from that in matched adjacent non-tumour tissues. ARID1A expression was significantly inversely correlated with tumour stage and distant metastasis, as well as poor overall survival in patients with osteosarcoma. Furthermore, ARID1A mRNA was down-regulated in four human osteosarcoma cell lines MG-63, U2OS, HOS and Saos-2. Restoring of ARID1A expression in MG-63 and U2OS cells significantly inhibited cell proliferation and metastasis in vitro. Collectively, our data demonstrate that ARID1A may serve as a tumour suppressor in osteosarcoma progression, and represent a valuable prognostic marker and potential therapeutic target for osteosarcoma.
http://ift.tt/2A36B6C
Adjuvant therapy in renal cell carcinoma: does higher risk for recurrence improve the chance for success?
Abstract
The success of targeted therapies, including inhibitors of the vascular endothelial growth factor pathway or the mammalian target of rapamycin, in the treatment of metastatic renal cell carcinoma (RCC) led to interest in testing their efficacy in the adjuvant setting. Results from the first trials are now available with other studies due to report imminently. This review provides an overview of adjuvant targeted therapy in RCC, including interpretation of currently available conflicting data and future direction of research.We discuss the key differences between the completed targeted therapy adjuvant trials, and highlight the importance of accurately identifying patients who are likely to benefit from adjuvant treatment. We also consider reasons why blinded independent radiology review and treatment dose may prove critical for adjuvant treatment success. The implications of using disease-free survival as a surrogate endpoint for overall survival from the patient perspective and measurement of health benefit have recently been brought into focus and are discussed. Finally, we discuss how the ongoing adjuvant trials with targeted therapies and checkpoint inhibitors may improve our understanding and ability to prevent tumor recurrence after nephrectomy in the future.http://ift.tt/2A9bPf9
Adjuvant therapy in renal cell carcinoma: does higher risk for recurrence improve the chance for success?
Abstract
The success of targeted therapies, including inhibitors of the vascular endothelial growth factor pathway or the mammalian target of rapamycin, in the treatment of metastatic renal cell carcinoma (RCC) led to interest in testing their efficacy in the adjuvant setting. Results from the first trials are now available with other studies due to report imminently. This review provides an overview of adjuvant targeted therapy in RCC, including interpretation of currently available conflicting data and future direction of research.We discuss the key differences between the completed targeted therapy adjuvant trials, and highlight the importance of accurately identifying patients who are likely to benefit from adjuvant treatment. We also consider reasons why blinded independent radiology review and treatment dose may prove critical for adjuvant treatment success. The implications of using disease-free survival as a surrogate endpoint for overall survival from the patient perspective and measurement of health benefit have recently been brought into focus and are discussed. Finally, we discuss how the ongoing adjuvant trials with targeted therapies and checkpoint inhibitors may improve our understanding and ability to prevent tumor recurrence after nephrectomy in the future.from Cancer via ola Kala on Inoreader http://ift.tt/2A9bPf9
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Cisplatin triggers cancer stem cell enrichment in platinum-resistant cells through NF-κB-TNFα-PIK3CA loop
Parallel to complex alteration in molecular and cellular events, enrichment of cancer stem cells (CSC) contributes significantly in deliberation and maintenance of cisplatin resistance. Cisplatin mediated CSC ...
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Hypermethylation and loss of retinoic acid receptor responder 1 expression in human choriocarcinoma
Human placental development resembles tumorigenesis, due to the invasive and fusogenic potential of trophoblasts. However, these features are tightly controlled in trophoblasts. Disturbance of this spatial and...
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ID1 promotes hepatocellular carcinoma proliferation and confers chemoresistance to oxaliplatin by activating pentose phosphate pathway
Drug resistance is one of the major concerns in the treatment of hepatocellular carcinoma (HCC). The aim of the present study was to determine whether aberrant high expression of the inhibitor of differentiati...
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Pilocytic astrocytoma with leptomeningeal spread in a patient with incontinentia pigmenti presenting with unilateral nystagmus
Abstract
Incontinentia pigmenti (IP) is a genetic disorder caused by mutations in IKBKG, leading to functional loss of nuclear factor kappa B (NF-ĸB). We report the case of a 6-month-old female child with IP who presented with unilateral nystagmus and was found to have a pilocytic astrocytoma with leptomeningeal spread. Enhanced understanding of the relationship between NF-ĸB, along with its upstream regulators, and tumorigenesis may shed light on whether a subset of patients with IP may be at increased risk for neoplasia.
http://ift.tt/2hOdCh4
Pilocytic astrocytoma with leptomeningeal spread in a patient with incontinentia pigmenti presenting with unilateral nystagmus
Abstract
Incontinentia pigmenti (IP) is a genetic disorder caused by mutations in IKBKG, leading to functional loss of nuclear factor kappa B (NF-ĸB). We report the case of a 6-month-old female child with IP who presented with unilateral nystagmus and was found to have a pilocytic astrocytoma with leptomeningeal spread. Enhanced understanding of the relationship between NF-ĸB, along with its upstream regulators, and tumorigenesis may shed light on whether a subset of patients with IP may be at increased risk for neoplasia.
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Phase II Study of Gemcitabine Plus Sirolimus in Previously Treated Patients with Advanced Soft-Tissue Sarcoma: a Spanish Group for Research on Sarcomas (GEIS) Study
Abstract
Background
Gemcitabine plus sirolimus enhances apoptosis in vitro and increases anti-tumor efficacy in vivo in soft-tissue sarcoma (STS) models.
Objective
The objective of this study was to evaluate the activity and toxicity of the combination of gemcitabine plus sirolimus in patients with STS after failure of standard chemotherapy.
Patients and Methods
Advanced STS patients, previously treated with doxorubicin and/or ifosfamide, were included in this single-arm phase II study. Patients received gemcitabine 800 mg/m2 intravenously (iv) at 10 mg/m2/min on days 1 and 8 every 3 weeks plus sirolimus 5 mg daily orally (po). After enrolment of the first 12 patients, the study protocol was amended due to toxicity and the starting dose of sirolimus was reduced to 3 mg daily po. Archival tumor samples were analyzed for extracellular signal-regulated kinase 1 and 2 (ERK1/2) expression and correlated with outcome. The primary endpoint was progression-free rate (PFR) at 3 months.
Results
From May 2012 to May 2013, 28 patients were enrolled at eight centers. PFR at 3 and 6 months was 44% and 20%, respectively, with 12 patients being free of progression at 3 months. Median progression-free survival (PFS) was 1.85 months (95% confidence interval [CI] 0.73–2.97) and median overall survival (OS) was 9.2 months (95% CI 5.8–12.5). No responses were observed. The most common grade 3–4 hematologic toxicities were neutropenia (48%) and leukopenia (41%) and the most frequent grade 3 non-hematologic toxicities were infection (18.5%), transaminitis (15%), fatigue (11%), and pneumonitis (11%). ERK1/2 expression was significantly correlated with PFS (p = 0.026).
Conclusions
The combination of gemcitabine and sirolimus is an active treatment in STS. Further investigation is warranted. ClinicalTrials.gov identifier: NCT01684449.
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