http://ift.tt/2Id7paD
Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Πέμπτη 8 Μαρτίου 2018
Fluorescence tumor imaging by i.v. administered indocyanine green in a mouse model of colitis-associated colon cancer
Summary
Fluorescence tumor imaging using exogenous fluorescent tumor-targeting agents has potential to improve early tumor detection. The fluorescent contrast agent indocyanine green (ICG) is used in medical diagnostics. The aim of the present study is to investigate the tumor imaging capability and the imaging mechanism of i.v. administered ICG in a mouse model of colitis-associated colon cancer. To do this, an azoxymethane/dextran sodium sulfate-induced colon cancer mouse model was used. Ex vivo imaging experiments were performed 1 hour after i.v. injection of ICG. ICG fluorescence was observed in the colon tumor tissues, with sufficient tumor to normal tissue ratio, correlating with tumor malignancy. In the tumor tissues, ICG fluorescence was localized in the vascular interstitial tissue. Immunofluorescence microscopy revealed that tumor cells formed tight junctions normally, suggesting an inability of tumor cellular uptake of ICG. In contrast, tumor tissues increased the CD31-immunoreactive endothelial cell area, and accumulated stromal cells immunoreactive for cyclooxygenase-2 (COX-2) and tumor cell population immunoreactive for inducible nitric oxide synthase (iNOS). vivo vascular permeability assay revealed that prostaglandin E2 promoted the endothelial cell permeability of ICG. In conclusion, our data demonstrated that fluorescence contrast-enhanced imaging following i.v. administered ICG can be applied to the detection of colon tumors in a mouse colitis-associated colon cancer model. The tumor tissue preference of ICG in the present model can be attributed to the enhanced vascular leakage of ICG involving inflammatory mediators, such as COX-2 and iNOS, in conjunction with increased tumor vascularity.
This article is protected by copyright. All rights reserved.
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CD169-positive sinus macrophages in the lymph nodes determine bladder cancer prognosis
Summary
CD169+ macrophages are suggested to play a pivotal role in establishing anti-tumor immunity. They capture dead tumor cell-associated antigens and transfer their information to lymphocytes including CD8+ T cells, which is important for successful tumor suppression. This study aimed to determine the prognostic significance of CD169+ macrophages residing in the tumor-draining lymph nodes from cases of bladder cancer. In this retrospective study, 44 bladder cancer patients who received radical cystectomy were examined. The abundance of CD169+ macrophages in the regional lymph nodes and the number of CD8+ T cells in the primary tumor were investigated by immunohistochemistry. A CD169 score was calculated based on the intensity of CD169 staining and the proportion of CD169+ macrophages, and the scores were compared to the patients' clinicopathological parameters. A high CD169 score was significantly associated with low T stage and with a high number of CD8+ T cells infiltrating into the tumor. The group with high CD169 expression had significantly longer cancer-specific survival than the group with low CD169 expression (5-year cancer-specific survival rate: 83.3% versus 31.3%). In a multivariate analysis, the CD169 score was identified as the strongest and independent favorable prognostic factor for cancer-specific survival. Our findings suggest that CD169+ macrophages in the lymph nodes enhance anti-tumor immunity by expanding CD8+ T cells in bladder cancer. The CD169 score may serve as a novel marker for the evaluation of bladder cancer prognosis.
This article is protected by copyright. All rights reserved.
http://ift.tt/2Hljvxb
A novel method for DNA methylation analysis using high-performance liquid chromatography and its clinical application
Summary
The aim of this study was to develop a new methodology that is suitable for DNA methylation diagnostics and to demonstrate its clinical applicability. We developed a new anion-exchange column for high-performance liquid chromatography (HPLC) with electrostatic and hydrophobic properties. Both cytosine and thymine, corresponding to methylated and unmethylated cytosine after bisulfite modification, respectively, are captured by electrostatic interaction and then discriminated from each other by their hydrophobic interactions. The DNA methylation levels of synthetic DNAs were quantified accurately and reproducibly within 10 minutes without time-consuming pretreatment of PCR products, and the measured values were unaffected by the distribution of methylated CpGs within the synthetic DNA fragments. When the DNA methylation status of the FAM150A gene, a marker of the CpG island methylator phenotype specific to clear cell renal cell carcinoma (ccRCC), was examined in 98 patients with ccRCCs, bulk specimens of tumorous tissue including cancer cells showing DNA methylation of the FAM150A gene were easily identifiable by simply viewing the differentiated chromatograms, even when the cancer cell content was low. Sixteen ccRCCs showing DNA methylation more frequently exhibited clinicopathological parameters reflecting tumor aggressiveness, i.e. a larger diameter, higher histological grade, vascular involvement, renal vein tumor thrombi, infiltrating growth, tumor necrosis, renal pelvis invasion and higher pathological Tumor-Node-Metastasis stage, and had significantly lower recurrence-free and overall survival rates. These data indicate that HPLC analysis using this newly developed anion-exchange column can be a powerful tool for DNA methylation diagnostics, including prognostication of patients with cancers, in a clinical setting.
This article is protected by copyright. All rights reserved.
http://ift.tt/2oWj1qm
Fluorescence tumor imaging by i.v. administered indocyanine green in a mouse model of colitis-associated colon cancer
Summary
Fluorescence tumor imaging using exogenous fluorescent tumor-targeting agents has potential to improve early tumor detection. The fluorescent contrast agent indocyanine green (ICG) is used in medical diagnostics. The aim of the present study is to investigate the tumor imaging capability and the imaging mechanism of i.v. administered ICG in a mouse model of colitis-associated colon cancer. To do this, an azoxymethane/dextran sodium sulfate-induced colon cancer mouse model was used. Ex vivo imaging experiments were performed 1 hour after i.v. injection of ICG. ICG fluorescence was observed in the colon tumor tissues, with sufficient tumor to normal tissue ratio, correlating with tumor malignancy. In the tumor tissues, ICG fluorescence was localized in the vascular interstitial tissue. Immunofluorescence microscopy revealed that tumor cells formed tight junctions normally, suggesting an inability of tumor cellular uptake of ICG. In contrast, tumor tissues increased the CD31-immunoreactive endothelial cell area, and accumulated stromal cells immunoreactive for cyclooxygenase-2 (COX-2) and tumor cell population immunoreactive for inducible nitric oxide synthase (iNOS). vivo vascular permeability assay revealed that prostaglandin E2 promoted the endothelial cell permeability of ICG. In conclusion, our data demonstrated that fluorescence contrast-enhanced imaging following i.v. administered ICG can be applied to the detection of colon tumors in a mouse colitis-associated colon cancer model. The tumor tissue preference of ICG in the present model can be attributed to the enhanced vascular leakage of ICG involving inflammatory mediators, such as COX-2 and iNOS, in conjunction with increased tumor vascularity.
This article is protected by copyright. All rights reserved.
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CD169-positive sinus macrophages in the lymph nodes determine bladder cancer prognosis
Summary
CD169+ macrophages are suggested to play a pivotal role in establishing anti-tumor immunity. They capture dead tumor cell-associated antigens and transfer their information to lymphocytes including CD8+ T cells, which is important for successful tumor suppression. This study aimed to determine the prognostic significance of CD169+ macrophages residing in the tumor-draining lymph nodes from cases of bladder cancer. In this retrospective study, 44 bladder cancer patients who received radical cystectomy were examined. The abundance of CD169+ macrophages in the regional lymph nodes and the number of CD8+ T cells in the primary tumor were investigated by immunohistochemistry. A CD169 score was calculated based on the intensity of CD169 staining and the proportion of CD169+ macrophages, and the scores were compared to the patients' clinicopathological parameters. A high CD169 score was significantly associated with low T stage and with a high number of CD8+ T cells infiltrating into the tumor. The group with high CD169 expression had significantly longer cancer-specific survival than the group with low CD169 expression (5-year cancer-specific survival rate: 83.3% versus 31.3%). In a multivariate analysis, the CD169 score was identified as the strongest and independent favorable prognostic factor for cancer-specific survival. Our findings suggest that CD169+ macrophages in the lymph nodes enhance anti-tumor immunity by expanding CD8+ T cells in bladder cancer. The CD169 score may serve as a novel marker for the evaluation of bladder cancer prognosis.
This article is protected by copyright. All rights reserved.
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A novel method for DNA methylation analysis using high-performance liquid chromatography and its clinical application
Summary
The aim of this study was to develop a new methodology that is suitable for DNA methylation diagnostics and to demonstrate its clinical applicability. We developed a new anion-exchange column for high-performance liquid chromatography (HPLC) with electrostatic and hydrophobic properties. Both cytosine and thymine, corresponding to methylated and unmethylated cytosine after bisulfite modification, respectively, are captured by electrostatic interaction and then discriminated from each other by their hydrophobic interactions. The DNA methylation levels of synthetic DNAs were quantified accurately and reproducibly within 10 minutes without time-consuming pretreatment of PCR products, and the measured values were unaffected by the distribution of methylated CpGs within the synthetic DNA fragments. When the DNA methylation status of the FAM150A gene, a marker of the CpG island methylator phenotype specific to clear cell renal cell carcinoma (ccRCC), was examined in 98 patients with ccRCCs, bulk specimens of tumorous tissue including cancer cells showing DNA methylation of the FAM150A gene were easily identifiable by simply viewing the differentiated chromatograms, even when the cancer cell content was low. Sixteen ccRCCs showing DNA methylation more frequently exhibited clinicopathological parameters reflecting tumor aggressiveness, i.e. a larger diameter, higher histological grade, vascular involvement, renal vein tumor thrombi, infiltrating growth, tumor necrosis, renal pelvis invasion and higher pathological Tumor-Node-Metastasis stage, and had significantly lower recurrence-free and overall survival rates. These data indicate that HPLC analysis using this newly developed anion-exchange column can be a powerful tool for DNA methylation diagnostics, including prognostication of patients with cancers, in a clinical setting.
This article is protected by copyright. All rights reserved.
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The role of primary lymph node sites in survival and mortality prediction in Hodgkin lymphoma: a SEER population-based retrospective study
Abstract
As diagnostic and therapeutic modalities for Hodgkin's Lymphoma (HL) continue to improve, patient-related factors affecting survival become more difficult to identify. Very little is known about the relationship between the primary site of lymph node (LN) involvement and survival of HL patients. We retrospectively analyzed the United States Surveillance, Epidemiology and End Results (SEER) database for 12,658 HL patients reported between 1973 and 2010 using survival analysis and time-interval multiple logistic regression (MLR) to disclose that relationship. The effect of all primary LN sites on the survival of HL patients was supported. The intra-abdominal (IAB) primary LN site was significantly associated with the worst survival. The pelvic (P) LN sites were significantly and independently associated with nearly 2 times and 2.5 times the probability of having 1-year overall mortality (OM) and 1-year cancer-specific mortality (CSM), respectively. Head, face and neck (HFN) primary LN sites were significant and independent predictors of better overall and HL-specific survival. A worse survival with the intra-abdominal primary LN site was probably related to their association with higher age, or advanced stages of HL. The biological basis behind the aggressiveness of intra-abdominal and pelvic LN sites is yet to be investigated.
Little is known about the role of primary lymph node sites in survival in Hodgkin lymphoma (HL). This study uses a huge population-based cohort using the SEER database. It was found that intra-abdominal LN sites predict the worst survival in HL patients and that pelvic LN sites were the most aggressive in predicting HL-specific 1-year mortality, and hence, we recommend that primary LN sites be added to future international prognostic scores for HL.
http://ift.tt/2GcgaRK
The role of primary lymph node sites in survival and mortality prediction in Hodgkin lymphoma: a SEER population-based retrospective study
Abstract
As diagnostic and therapeutic modalities for Hodgkin's Lymphoma (HL) continue to improve, patient-related factors affecting survival become more difficult to identify. Very little is known about the relationship between the primary site of lymph node (LN) involvement and survival of HL patients. We retrospectively analyzed the United States Surveillance, Epidemiology and End Results (SEER) database for 12,658 HL patients reported between 1973 and 2010 using survival analysis and time-interval multiple logistic regression (MLR) to disclose that relationship. The effect of all primary LN sites on the survival of HL patients was supported. The intra-abdominal (IAB) primary LN site was significantly associated with the worst survival. The pelvic (P) LN sites were significantly and independently associated with nearly 2 times and 2.5 times the probability of having 1-year overall mortality (OM) and 1-year cancer-specific mortality (CSM), respectively. Head, face and neck (HFN) primary LN sites were significant and independent predictors of better overall and HL-specific survival. A worse survival with the intra-abdominal primary LN site was probably related to their association with higher age, or advanced stages of HL. The biological basis behind the aggressiveness of intra-abdominal and pelvic LN sites is yet to be investigated.
Little is known about the role of primary lymph node sites in survival in Hodgkin lymphoma (HL). This study uses a huge population-based cohort using the SEER database. It was found that intra-abdominal LN sites predict the worst survival in HL patients and that pelvic LN sites were the most aggressive in predicting HL-specific 1-year mortality, and hence, we recommend that primary LN sites be added to future international prognostic scores for HL.
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Pediatric versus adult meningioma: comparison of epidemiology, treatments, and outcomes using the Surveillance, Epidemiology, and End Results database
Abstract
Pediatric meningiomas, which account for < 1% of all meningiomas, are thought to have unique features, including being more aggressive than their adult counterparts. The goal of this investigation was to compare pediatric and adult meningiomas in a large head-to-head comparison. We used the Surveillance, Epidemiology, and End Result (SEER) datasets to compare meningioma demographics, first treatments, and outcomes among children/adolescents (0–21 years), young adults (22–45 years), and older adults (> 45 years). During 2004–2012, SEER contained 59148 patients age 0–107 years diagnosed with meningioma, with children/adolescents accounting for 381 (0.64%) patients. Unlike older and young adults, children/adolescents with meningioma did not demonstrate female predominance, and had an equal 1:1 male-to-female ratio. Children/adolescents also had almost three-times as many spinal tumors (13.1%) than young adults (4.2%) and older adults (4.4%). Both children/adolescents and young adults had undergone more gross total resections (both 43%) versus older adults (25%), and were treated more with radiation (14.6%, and 12.0% respectively) than their older counterparts (8.5%). In addition, both children/adolescents and young adults had significantly lower all-cause mortality (4.5% in both) than older adults (24.6%), during median 35-month follow-up. Inherent limitations of the SEER datasets restrict our ability to answer important questions regarding comparisons of tumor grading, histological diagnosis, cause-specific mortality, and neurofibromatosis status. Pediatric meningiomas appear distinct from their adult counterparts as they do not display the typical female predominance and include more clinically relevant spinal tumors. More extensive surgeries, greater use of radiation therapy, and lower all-cause mortality were seen in both children/adolescents and young adults, which raises questions regarding the perceived uniquely aggressive nature of pediatric meningiomas. However, due to the significant limitations of the SEER datasets, our results must be interpreted cautiously and stand only to foster novel questions, which would be better answered in well-designed, prospective studies.
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Pediatric versus adult meningioma: comparison of epidemiology, treatments, and outcomes using the Surveillance, Epidemiology, and End Results database
Abstract
Pediatric meningiomas, which account for < 1% of all meningiomas, are thought to have unique features, including being more aggressive than their adult counterparts. The goal of this investigation was to compare pediatric and adult meningiomas in a large head-to-head comparison. We used the Surveillance, Epidemiology, and End Result (SEER) datasets to compare meningioma demographics, first treatments, and outcomes among children/adolescents (0–21 years), young adults (22–45 years), and older adults (> 45 years). During 2004–2012, SEER contained 59148 patients age 0–107 years diagnosed with meningioma, with children/adolescents accounting for 381 (0.64%) patients. Unlike older and young adults, children/adolescents with meningioma did not demonstrate female predominance, and had an equal 1:1 male-to-female ratio. Children/adolescents also had almost three-times as many spinal tumors (13.1%) than young adults (4.2%) and older adults (4.4%). Both children/adolescents and young adults had undergone more gross total resections (both 43%) versus older adults (25%), and were treated more with radiation (14.6%, and 12.0% respectively) than their older counterparts (8.5%). In addition, both children/adolescents and young adults had significantly lower all-cause mortality (4.5% in both) than older adults (24.6%), during median 35-month follow-up. Inherent limitations of the SEER datasets restrict our ability to answer important questions regarding comparisons of tumor grading, histological diagnosis, cause-specific mortality, and neurofibromatosis status. Pediatric meningiomas appear distinct from their adult counterparts as they do not display the typical female predominance and include more clinically relevant spinal tumors. More extensive surgeries, greater use of radiation therapy, and lower all-cause mortality were seen in both children/adolescents and young adults, which raises questions regarding the perceived uniquely aggressive nature of pediatric meningiomas. However, due to the significant limitations of the SEER datasets, our results must be interpreted cautiously and stand only to foster novel questions, which would be better answered in well-designed, prospective studies.
http://ift.tt/2IgkShN
Stability of matrix metalloproteinase-9 as biological marker in colorectal cancer
Abstract
Matrix metalloproteinases (MMPs) are believed to be of importance in the growth and spread of colorectal cancer (CRC). MMP-9 level has been suggested as a biological predictor of prognosis in CRC as well as in other types of cancer such as breast and cervical cancer. The purpose of this study was to investigate the stability over time of MMP-9 in cryopreserved plasma, colorectal tumor tissue extract and macroscopically tumor-free colon mucosa tissue extract samples. Plasma and tissue samples were taken from patients at primary CRC surgery and analyzed for MMP-9. Aliquots of samples from the same patients were stored at – 80 °C pending analysis. These aliquots were analyzed using identical methods after storage periods of nine (plasma) and twelve (tissue) years. No significant difference in plasma MMP-9 concentration was seen between baseline samples and those after 9 years of cryopreservation (median values 9.9 and 9.7 ng/mL, respectively; p > 0.05). MMP-9 levels in the tumor-free tissue extracts had increased to baseline (median values 7.1 and 8.1 ng/mL, respectively; p < 0.01). MMP-9 levels in the tumor tissue extracts had also increased significantly (median values 89.9 and 133.5 ng/mL, respectively; p < 0.01). We have demonstrated that MMP-9 levels in frozen citrated plasma are stable if stored at − 80 °C, whereas MMP-9 levels in extracts from tumor tissue and tumor-free intestinal mucosa appear to increase with time. We conclude that MMP-9 levels in cryopreserved plasma may be considered stable over time and are thus suitable for comparison purposes in consecutive series.
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Stability of matrix metalloproteinase-9 as biological marker in colorectal cancer
Abstract
Matrix metalloproteinases (MMPs) are believed to be of importance in the growth and spread of colorectal cancer (CRC). MMP-9 level has been suggested as a biological predictor of prognosis in CRC as well as in other types of cancer such as breast and cervical cancer. The purpose of this study was to investigate the stability over time of MMP-9 in cryopreserved plasma, colorectal tumor tissue extract and macroscopically tumor-free colon mucosa tissue extract samples. Plasma and tissue samples were taken from patients at primary CRC surgery and analyzed for MMP-9. Aliquots of samples from the same patients were stored at – 80 °C pending analysis. These aliquots were analyzed using identical methods after storage periods of nine (plasma) and twelve (tissue) years. No significant difference in plasma MMP-9 concentration was seen between baseline samples and those after 9 years of cryopreservation (median values 9.9 and 9.7 ng/mL, respectively; p > 0.05). MMP-9 levels in the tumor-free tissue extracts had increased to baseline (median values 7.1 and 8.1 ng/mL, respectively; p < 0.01). MMP-9 levels in the tumor tissue extracts had also increased significantly (median values 89.9 and 133.5 ng/mL, respectively; p < 0.01). We have demonstrated that MMP-9 levels in frozen citrated plasma are stable if stored at − 80 °C, whereas MMP-9 levels in extracts from tumor tissue and tumor-free intestinal mucosa appear to increase with time. We conclude that MMP-9 levels in cryopreserved plasma may be considered stable over time and are thus suitable for comparison purposes in consecutive series.
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The effect of neoadjuvant androgen deprivation therapy on tumour hypoxia in high-grade prostate cancer: a 18F-MISO PET/MRI imaging study.
Publication date: Available online 8 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Ismini C. Mainta, Thomas Zilli, Jean-Christophe Tille, Thomas De Perrot, Jean-Paul Vallée, Franz Buchegger, Valentina Garibotto, Raymond Miralbell
PurposeTumour hypoxia is associated with radio-resistance and poor prognosis after radiotherapy (RT) for prostate cancer (PCa). In this prospective pilot study we assessed the ability of 18F-misonidazole (18F-MISO) PET/MRI to detect hypoxia in high-grade PCa patients candidates for curative RT and we evaluated 18F-MISO PET/MRI modulation after 3 months of neoadjuvant androgen-deprivation therapy (nADT).MethodsEleven PCa patients with Gleason score (GS) ≥8 underwent 18F-Choline (18F-FCH) PET/CT at diagnosis and two 18F-MISO hybrid PET/MRI before and after 3 months of nADT, respectively. Immunohistochemistry (IHC) for tissue hypoxia and proliferation-related biomarkers (Glut1, CA-IX, VEGF-A, Ki67, HIF-1-alpha, EGFR) was performed in lesions bearing the highest GS. We used non-parametric tests to assess: 1. the presence of 18F-MISO positive regions (Tumour-to-Background ratios - TBR ≥ 1.4) at baseline; 2. The correlation between imaging parameters (PET tracers uptake, Prostate Imaging Reporting and Data System (PIRADS) scores, dynamic contrast enhancement perfusion markers) at baseline; 3. The difference in IHC staining between 18F-MISO positive and 18F-MISO negative lesions; 4. The changes in 18F-MISO PET/MRI imaging after nADT.Results18F-MISO uptake was significant in 7 patients, 5 of them being coincidental with the highest GS region. A significant correlation was found at baseline between GS and 18F-MISO TBR, between 18F-MISO TBR and MRI perfusion markers, between GS and 18F-FCH SUVmax, between GS and PIRADS and between 18F-FCH SUVmax and PIRADS. No difference was found between 18F-MISO positive and negative biopsies with respect to tissue biomarkers. 18F-MISO TBR diminished significantly after nADT only in high-grade lesions and in regions with a significant uptake at baseline.Conclusions18F-MISO PET imaging showed variable uptake in PCa, associated with a higher GS, lowering significantly after 3 months of nADT in high grade lesions. These results suggest the existence of a hypoxic microenvironment in PCa and a re-oxygenation effect of nADT.
Teaser
Tumour hypoxia is associated to treatment resistance. In this prospective study of 11 patients, we evaluated the occurrence of hypoxia in high-grade prostate cancer by multiparametric integrated18F-MISO PET/MRI before and after 3 months of androgen deprivation. Our results show the presence of hypoxic conditions in prostate carcinoma, correlated with tumour grade and responding to androgen ablation, thus supporting the re-oxygenation role of a neoadjuvant androgen deprivation therapy phase in combination with curative radiotherapy.from Cancer via ola Kala on Inoreader http://ift.tt/2IdFhE5
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Hypopituitarism after Single-Fraction Pituitary Adenoma Radiosurgery: Dosimetric Analysis based on Patients treated Using Contemporary Techniques
Publication date: Available online 8 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Christopher S. Graffeo, Michael J. Link, Paul D. Brown, William F. Young, Bruce E. Pollock
PurposeHypopituitarism is the most frequent complication after pituitary adenoma radiosurgery (SRS). The dosimetric factors associated with pituitary insufficiency remain unclear despite more than 30 years of clinical usage.Methods and MaterialsRetrospective review of 97 patients having single-fraction SRS from 2007 until 2014. Eligible patients had no history of prior radiation, normal age- and gender-specific pituitary function before SRS, and at least 24 months of endocrine follow-up. Forty patients (41%) had hormone secreting tumors; 57 patients had non-secreting tumors (59%). The median prescription isodose volume was 2.8 cm3 (IQR, 1.3-4.7); the median tumor margin dose was 20 Gy (IQR, 15-25).ResultsThe median follow-up after SRS was 48 months (IQR, 34-68). Twenty-seven patients (28%) developed pituitary insufficiency at a median of 22 months (IQR, 12-36) after SRS. The rate of new endocrine deficits was 17% at 2-years (95% CI 10%-25%) and 31% at 5-years (95% CI 20%-42%). Male sex (HR=2.38, 95% CI 1.05-5.26, P=0.04), smaller pituitary gland volume (HR=0.99, 95% CI 0.99-0.99, P=0.01), and higher mean pituitary gland dose (HR=1.31, 95% CI 1.16-1.47, P<0.001) were associated with post-SRS hypopituitarism in multivariable analysis. The rate of hypopituitarism for patients with a mean gland dose <11.0 Gy at 2-years was 2% (95% CI 0%-4%) and 5-years was 5% (95% CI 0%-11%) whereas rate of hypopituitarism for patients with a mean gland dose ≥11.0 Gy at 2-years was 31% (95% CI 17%-43%) and at 5-years was 51% (95% CI 34%-65%).ConclusionsHypopituitarism after pituitary adenoma SRS increases in a time- and dose-dependent manner. Reducing the radiation exposure to the identifiable gland to a mean dose <11.0 Gy whenever feasible may lower the incidence of new hormonal deficits after pituitary adenoma SRS.
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The effect of neoadjuvant androgen deprivation therapy on tumour hypoxia in high-grade prostate cancer: a 18F-MISO PET/MRI imaging study.
Publication date: Available online 8 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Ismini C. Mainta, Thomas Zilli, Jean-Christophe Tille, Thomas De Perrot, Jean-Paul Vallée, Franz Buchegger, Valentina Garibotto, Raymond Miralbell
PurposeTumour hypoxia is associated with radio-resistance and poor prognosis after radiotherapy (RT) for prostate cancer (PCa). In this prospective pilot study we assessed the ability of 18F-misonidazole (18F-MISO) PET/MRI to detect hypoxia in high-grade PCa patients candidates for curative RT and we evaluated 18F-MISO PET/MRI modulation after 3 months of neoadjuvant androgen-deprivation therapy (nADT).MethodsEleven PCa patients with Gleason score (GS) ≥8 underwent 18F-Choline (18F-FCH) PET/CT at diagnosis and two 18F-MISO hybrid PET/MRI before and after 3 months of nADT, respectively. Immunohistochemistry (IHC) for tissue hypoxia and proliferation-related biomarkers (Glut1, CA-IX, VEGF-A, Ki67, HIF-1-alpha, EGFR) was performed in lesions bearing the highest GS. We used non-parametric tests to assess: 1. the presence of 18F-MISO positive regions (Tumour-to-Background ratios - TBR ≥ 1.4) at baseline; 2. The correlation between imaging parameters (PET tracers uptake, Prostate Imaging Reporting and Data System (PIRADS) scores, dynamic contrast enhancement perfusion markers) at baseline; 3. The difference in IHC staining between 18F-MISO positive and 18F-MISO negative lesions; 4. The changes in 18F-MISO PET/MRI imaging after nADT.Results18F-MISO uptake was significant in 7 patients, 5 of them being coincidental with the highest GS region. A significant correlation was found at baseline between GS and 18F-MISO TBR, between 18F-MISO TBR and MRI perfusion markers, between GS and 18F-FCH SUVmax, between GS and PIRADS and between 18F-FCH SUVmax and PIRADS. No difference was found between 18F-MISO positive and negative biopsies with respect to tissue biomarkers. 18F-MISO TBR diminished significantly after nADT only in high-grade lesions and in regions with a significant uptake at baseline.Conclusions18F-MISO PET imaging showed variable uptake in PCa, associated with a higher GS, lowering significantly after 3 months of nADT in high grade lesions. These results suggest the existence of a hypoxic microenvironment in PCa and a re-oxygenation effect of nADT.
Teaser
Tumour hypoxia is associated to treatment resistance. In this prospective study of 11 patients, we evaluated the occurrence of hypoxia in high-grade prostate cancer by multiparametric integrated18F-MISO PET/MRI before and after 3 months of androgen deprivation. Our results show the presence of hypoxic conditions in prostate carcinoma, correlated with tumour grade and responding to androgen ablation, thus supporting the re-oxygenation role of a neoadjuvant androgen deprivation therapy phase in combination with curative radiotherapy.http://ift.tt/2IdFhE5
Hypopituitarism after Single-Fraction Pituitary Adenoma Radiosurgery: Dosimetric Analysis based on Patients treated Using Contemporary Techniques
Publication date: Available online 8 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Christopher S. Graffeo, Michael J. Link, Paul D. Brown, William F. Young, Bruce E. Pollock
PurposeHypopituitarism is the most frequent complication after pituitary adenoma radiosurgery (SRS). The dosimetric factors associated with pituitary insufficiency remain unclear despite more than 30 years of clinical usage.Methods and MaterialsRetrospective review of 97 patients having single-fraction SRS from 2007 until 2014. Eligible patients had no history of prior radiation, normal age- and gender-specific pituitary function before SRS, and at least 24 months of endocrine follow-up. Forty patients (41%) had hormone secreting tumors; 57 patients had non-secreting tumors (59%). The median prescription isodose volume was 2.8 cm3 (IQR, 1.3-4.7); the median tumor margin dose was 20 Gy (IQR, 15-25).ResultsThe median follow-up after SRS was 48 months (IQR, 34-68). Twenty-seven patients (28%) developed pituitary insufficiency at a median of 22 months (IQR, 12-36) after SRS. The rate of new endocrine deficits was 17% at 2-years (95% CI 10%-25%) and 31% at 5-years (95% CI 20%-42%). Male sex (HR=2.38, 95% CI 1.05-5.26, P=0.04), smaller pituitary gland volume (HR=0.99, 95% CI 0.99-0.99, P=0.01), and higher mean pituitary gland dose (HR=1.31, 95% CI 1.16-1.47, P<0.001) were associated with post-SRS hypopituitarism in multivariable analysis. The rate of hypopituitarism for patients with a mean gland dose <11.0 Gy at 2-years was 2% (95% CI 0%-4%) and 5-years was 5% (95% CI 0%-11%) whereas rate of hypopituitarism for patients with a mean gland dose ≥11.0 Gy at 2-years was 31% (95% CI 17%-43%) and at 5-years was 51% (95% CI 34%-65%).ConclusionsHypopituitarism after pituitary adenoma SRS increases in a time- and dose-dependent manner. Reducing the radiation exposure to the identifiable gland to a mean dose <11.0 Gy whenever feasible may lower the incidence of new hormonal deficits after pituitary adenoma SRS.
http://ift.tt/2p1lM9j
Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project
Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project
Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project, Published online: 09 March 2018; doi:10.1038/s41416-018-0007-z
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Physical activity, sedentary behaviour and colorectal cancer risk in the UK Biobank
Physical activity, sedentary behaviour and colorectal cancer risk in the UK Biobank
Physical activity, sedentary behaviour and colorectal cancer risk in the UK Biobank, Published online: 08 March 2018; doi:10.1038/bjc.2017.496
Physical activity, sedentary behaviour and colorectal cancer risk in the UK Biobankfrom Cancer via ola Kala on Inoreader http://ift.tt/2oUJswB
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Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project
Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project
Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project, Published online: 09 March 2018; doi:10.1038/s41416-018-0007-z
Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Projecthttp://ift.tt/2oYgISM
Physical activity, sedentary behaviour and colorectal cancer risk in the UK Biobank
Physical activity, sedentary behaviour and colorectal cancer risk in the UK Biobank
Physical activity, sedentary behaviour and colorectal cancer risk in the UK Biobank, Published online: 08 March 2018; doi:10.1038/bjc.2017.496
Physical activity, sedentary behaviour and colorectal cancer risk in the UK Biobankhttp://ift.tt/2oUJswB
Accelerating the Pace of Cancer Prevention- Right Now
As a nation, we underinvest in prevention and fail to implement strategies that ensure all population groups equitably share in the return on investment in prevention research and the benefits of prevention effectiveness. There is significant evidence indicating that by applying knowledge that we already have to reduce tobacco, inactivity, and obesity (known modifiable causes of cancer), we can prevent more than 50% of cancers. Vaccination against HPV, aspirin and selective estrogen receptor modulators, and screening programs further reduce risk. Evidence-based prevention strategies are inconsistently implemented across the United States. Substantial variation across States indicates that there is much room for improvement in implementation of prevention. Implementation science applies innovative approaches to identifying, understanding, and developing strategies for overcoming barriers to the adoption, adaptation, integration, scale-up, and sustainability of evidence-based interventions, tools, policies, and guidelines that will prevent cancer through application of evidence-based interventions. When we get implementation of prevention programs right and at scale, we achieve substantial population benefits. Although many efforts are underway to maximize our knowledge about the causes and treatments of cancer, we can achieve reductions in the cancer burden right now by doing what we already know. The time to start is now. Cancer Prev Res; 1–11. ©2018 AACR.
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A phase I trial of escalating doses of cixutumumab (IMC-A12) and sorafenib in the treatment of advanced hepatocellular carcinoma
Abstract
Purpose
The insulin-like growth factor (IGF) pathway is activated in hepatocarcinogenesis. Cixutumumab is a monoclonal antibody against human insulin-like growth factor-1 receptor (IGF-1R). Given the cross-talk between the IGF and VEGF pathways, we performed a phase I study of the combination of cixutumumab and sorafenib in hepatocellular cancer (HCC).
Methods
Eligible patients with no prior systemic therapy for advanced HCC and Child–Pugh A to B7 were treated with sorafenib 400 mg BID and escalating doses of cixutumumab (2, 4, or 6 mg/kg IV weekly) in a 3 + 3 design. Dose limiting toxicity (DLT) was defined as treatment-related grade 3 or 4 non-hematologic toxicity (except for a subset of manageable toxicities) or any grade 4 hematologic toxicities.
Results
In 21 patients enrolled, there were 3 DLTs; grade 3 hyperglycemia, grade 3 hypophosphatemia, and grade 5 peritonitis. The maximum tolerated dose of cixutumumab was 4 mg/kg IV weekly with standard dose sorafenib. Eighteen of 21 (86%) patients had grade 3 or above toxicities attributed to treatment. One patient also experienced grade 4 colonic perforation and grade 5 peritonitis. The median number of cycles completed was 4 (0–26). Of 16 patients evaluable for response, 81% achieved stable disease. The median progression free survival was 6.0 months (95% CI 3.6–undefined) and the median overall survival was 10.5 months (95% CI 7.1–undefined).
Conclusions
While the combination of cixutumumab and sorafenib had a toxicity profile similar to that of sorafenib monotherapy, it manifested limited clinical efficacy in unselected patients with HCC.
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Remembering Professor Stanley Dische (1927–2017)
Prof Stanley Dische, one of the great pioneers of modern radiotherapy, sadly died on 2nd November 2017 at the age of 90 years. Stanley Dische was born in London on 27th March 1927 and qualified in medicine from the Middlesex Hospital Medical School, London, in 1950. He worked initially as an Assistant Pathologist in the Bland Sutton Institute of Pathology at the Middlesex Hospital and subsequently as Pathologist to the Royal Air Force Institute of Pathology and Tropical Medicine. During this time he completed his research for his MD thesis entitled 'The investigation of symptomless glycosuria'.
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A phase I trial of escalating doses of cixutumumab (IMC-A12) and sorafenib in the treatment of advanced hepatocellular carcinoma
Abstract
Purpose
The insulin-like growth factor (IGF) pathway is activated in hepatocarcinogenesis. Cixutumumab is a monoclonal antibody against human insulin-like growth factor-1 receptor (IGF-1R). Given the cross-talk between the IGF and VEGF pathways, we performed a phase I study of the combination of cixutumumab and sorafenib in hepatocellular cancer (HCC).
Methods
Eligible patients with no prior systemic therapy for advanced HCC and Child–Pugh A to B7 were treated with sorafenib 400 mg BID and escalating doses of cixutumumab (2, 4, or 6 mg/kg IV weekly) in a 3 + 3 design. Dose limiting toxicity (DLT) was defined as treatment-related grade 3 or 4 non-hematologic toxicity (except for a subset of manageable toxicities) or any grade 4 hematologic toxicities.
Results
In 21 patients enrolled, there were 3 DLTs; grade 3 hyperglycemia, grade 3 hypophosphatemia, and grade 5 peritonitis. The maximum tolerated dose of cixutumumab was 4 mg/kg IV weekly with standard dose sorafenib. Eighteen of 21 (86%) patients had grade 3 or above toxicities attributed to treatment. One patient also experienced grade 4 colonic perforation and grade 5 peritonitis. The median number of cycles completed was 4 (0–26). Of 16 patients evaluable for response, 81% achieved stable disease. The median progression free survival was 6.0 months (95% CI 3.6–undefined) and the median overall survival was 10.5 months (95% CI 7.1–undefined).
Conclusions
While the combination of cixutumumab and sorafenib had a toxicity profile similar to that of sorafenib monotherapy, it manifested limited clinical efficacy in unselected patients with HCC.
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Double vascularized omentum lymphatic transplant (VOLT) for the treatment of lymphedema
Background and Objectives
Orthotopic vascularized lymph node transplant has been successfully used to treat lymphedema. A second, heterotopic lymph node transplant in the distal extremity may provide further improvement. The vascularized omentum lymphatic transplant (VOLT) provides adequate tissue for two simultaneous flap transfers to one limb. The purpose of this study was to review our experience with this technique.
Methods
We conducted a retrospective study of patients who underwent VOLT, with a subgroup analysis of patients who underwent double VOLT. Technical aspects of the procedure, complications, and early outcomes were reviewed.
Results
From May 2015 to August 2017, 54 VOLTs were performed in 38 patients, of whom 16 received double VOLT. Among patients in the double VOLT group with postoperative imaging at 1 year, uptake into the transplanted omentum was seen in three of six (50%) patients on lymphoscintigraphy and in one of five (20%) patients on indocyanine green lymphangiography. One patient (3.1%) in the double VOLT group required a return to the operating room. There were no donor site complications in the double VOLT group. The overall complication rate was 15.8%.
Conclusions
Double VOLT to the mid-level and proximal extremity is a safe and viable option.
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Ampullary adenocarcinoma: Defining predictors of survival and the impact of adjuvant therapy following surgical resection for stage I disease
Background and Objectives
Outcomes and recommendations regarding adjuvant therapy (AT) for stage I ampullary adenocarcinoma (AAC) are inadequately described. We sought to determine factors associated with survival and better define the impact of AT.
Methods
The NCDB was queried for stage I AAC patients undergoing resection. We evaluated variables influencing the administration of AT and affecting survival, including the receipt of AT.
Results
Five hundred thirty-seven patients were identified. 1, 3, and 5-year OS were 91.3%, 78.8%, and 67.4%, respectively. 103 received AT: 101 chemotherapy, 31 radiation, and 29 a combination of both. AT was more commonly utilized in patients with poorly differentiated and T2 tumors. Comorbid disease was inversely associated with use of AT. Age ≥65 was associated with decreased survival for stage IA and IB, while positive resection margins and sampling of <12 LNs were associated with decreased OS for stage IA and IB, respectively. After propensity matching key covariates, no significant difference in OS was observed between those receiving and not receiving AT (P = 0.449).
Conclusion
This analysis revealed a modest 5-year OS for stage I AAC. Age, positive resection margins, and evaluation of <12 LNs negatively influenced OS and AT did not convey a survival benefit.
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Chromatin organisation and cancer prognosis
Håvard Emil Danielsen joins The Lancet Oncology to discuss his latest paper on machine learning algorithms to analyse chromatin organisation as a prognostic marker for cancer.
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Fast and robust adaptation of organs-at-risk delineations from planning scans to match daily anatomy in pre-treatment scans for online-adaptive radiotherapy of abdominal tumors
To validate a novel deformable image registration (DIR) method for online adaptation of planning organ-at-risk (OAR) delineations to match daily anatomy during hypo-fractionated RT of abdominal tumors.
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Targeting BCL-2 in Hematologic Malignancies
Abstract
Resistance to apoptosis is one of the hallmarks of cancer and members of the B-cell lymphoma 2 (BCL-2) family of proteins are central regulators of apoptosis. Many cancers become resistant to chemotherapy and apoptosis by up-regulating BCL-2 and other family members, making these proteins attractive targets for cancer therapy. Venetoclax is an orally administered, small-molecule apoptosis stimulant that targets BCL-2 proteins by acting as a BCL-2 homology domain 3 (BH3) mimetic. The drug is approved in the USA and EU as a monotherapy for the for the treatment of certain patients with chronic lymphocytic leukemia (CLL) and is in phase III clinical development for multiple myeloma (MM), and in phase II or I/II clinical trials for acute myeloid leukemia, and several B-cell malignancies, including diffuse large B-cell lymphoma, Waldenstrom's macroglobulinaemia, follicular lymphoma, and mantle-cell lymphoma.
http://ift.tt/2G7KY66
Diagnostic Model of Serum miR-193a-5p, HE4 and CA125 Improves the Diagnostic Efficacy of Epithelium Ovarian Cancer
Abstract
Epithelium ovarian cancer (EOC) is currently the prevalent malignant cancer worldwide. However, there is a lack of efficient biomarkers for EOC screening. Accumulating evidence reveals that serum miRNA detectable in various types of cancer. Therefore, we explore the diagnostic value of combined detection of plasma miR-193a-5p, HE4 and CA125 for EOC. Serum samples were collected from 45 patients with primary EOC, 30 patients with benign ovarian tumor patients and 40 healthy controls. The expression of serum miR-193a-5p was detected by real-time quantitative PCR, and serum HE4 and CA125 were detected by chemiluminescent immunoassay. Moreover, a diagnostic model combining miR-193a-5p, HE4 and CA125 or alone in EOC patients was evaluated by ROC curve analysis. The relative expression quantity (RQ) of serum miR-193a-5p in EOC patients, benign ovarian tumor patients and healthy control groups were 0.419 (0.093, 2.215), 3.667 (1.633, 6.691) and 1.130 (1.000, 7.087), respectively. The RQ of serum miR-193a-5p in EOC patients was significantly lower than that in benign ovarian tumor patients and healthy controls (both P < 0.001), and there was no significant difference between benign ovarian tumor patients and healthy controls (both P > 0.05). There was no significant correlation between serum miR-193-5p, HE4 and CA125 levels (both P > 0.05). Additionally a risk model for miR-193a-5p, HE4 and CA125 was correlated with Grading and Lymph node metastasis (P = 0.016, P = 0.029). The area under the receiver operating characteristic curve of a risk model for distinguishing EOC patients from healthy individuals was 0.996, which higher than any single biomarker. Combined detection of miR-193-5p, HE4 and CA125 by logistic regression analysis could greatly improved the diagnostic ability of EOC and may prove to be a candidate biomarker, providing new directions for further investigation.
http://ift.tt/2G7IrJ4
Preradiotherapy Tumor Volume in Local Control of Squamous Cell Carcinoma of the Supraglottic Larynx
Objectives: Examine the utility of pretreatment computed tomography in predicting local control (LC) in squamous cell carcinoma of the supraglottic larynx treated with primary radiotherapy (RT). Methods: In total, 167 patients treated between 1983 and 2013 were reviewed. Patients had received pretreatment diagnostic computed tomographic imaging of the larynx and neck from which primary tumor volume (PrTV) was delineated. LC, larynx function at last follow-up, and RT complications were recorded. PrTV was evaluated with respect to outcome. Results: In this study, median age was 61 years, and mean follow-up was 96 months. In total, 43% had T1-T2, 46% had T3, and 11% had T4 disease; 49% had N0 disease. Median tumor volume, 5.1 cm3 (0.4 to 188 cm3). Mean dose, 74 Gy; 20% received concurrent chemotherapy. Overall, 10-year LC was 78.9%. Ten-year LC stratified by tumor volume was: 0 to 4.9 cm3, 90.8%; 5 to 8.9 cm3, 67.3%; and >9 cm3, 69.4%. Ten-year LC with preserved larynx function was: 0 to 4.9 cm3, 76.7%; 5 to 8.9 cm3, 61.5%; and >9 cm3, 53.4%. LC and LC with preserved larynx function was significantly different between PrTV groups (P
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http://ift.tt/2trrjeN
Impact of Health Insurance Status on Prostate Cancer Treatment Modality Selection in the United States
Objectives: A variety of treatment modalities are available for the management of clinically localized prostate cancer in the United States. In addition to clinical factors, treatment modality choice may be influenced by a patient's insurance status. Using a national data set, we investigated the relationship between insurance status and prostate cancer treatment modality selection among nonelderly men in the United States. Methods: Nonelderly men age 18 to 64 years treated for localized prostate cancer from 2010 to 2014 were identified within the National Cancer Database. Patients with no insurance, Medicaid, or private insurance were included. The χ2 and multivariable logistic regression analyses were used to evaluate the association of insurance status, other demographic and facility factors, and D'Amico risk classification with treatment modality. Results: We identified 135,937 patients with either no insurance (2.8%), Medicaid (4.2%), or private insurance (92.9%) treated for prostate cancer who underwent cancer-directed treatment or active surveillance between 2010 and 2014. Patients with private insurance were more likely to receive minimally invasive surgery (61.4% vs. 35.4%, respectively; P
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http://ift.tt/2Dbrquj
Overall Survival Results of the Feasibility Study of Adjuvant Chemotherapy With Docetaxel Plus Cisplatin Followed by Long-term Single-agent Administration of S-1 in Patients With Completely Resected Non–Small Cell Lung Cancer: Thoracic Oncology Research Group (TORG) 0809
Objectives: The TORG0809 study was a multicenter feasibility study of long-term single-agent therapy with S-1 after docetaxel plus cisplatin therapy in patients with completely resected stage II or stage IIIA non–small cell lung cancer. We report the results of the final overall survival (OS) analysis. Patients and Methods: A total of 129 eligible patients received 3 cycles of docetaxel (60 mg/m2, day 1) plus cisplatin (80 mg/m2, day 1), followed by S-1 at 40 mg/m2 twice daily for 14 consecutive days, for >6 months (maximum, 1 y). Results: At the cutoff date of April 13, 2016, the median follow-up time was 6.0 years. Of the 129 patients, 43 had died, and 74 patients developed disease recurrence or died. The median OS had not been reached. The 5-year OS rate was 71% [95% confidence interval (CI), 62-78]. The 5-year OS rates in the patients with stage II and stage IIIA were 76% and 68%, respectively. The median recurrence-free survival (RFS) duration was 3.4 years (95% CI, 2.3-5.7). The 5-year RFS rate was 44% (95% CI, 36-53). The 5-year RFS rates in patients with stage II and stage IIIA disease were 57% and 38%, respectively. Disease recurrence occurred in 68 patients, and 62 of these patients received second-line chemotherapy. The most common sites of recurrence were the brain (n=22) and mediastinal lymph nodes (n=22). Conclusion: The survival data obtained from this study are promising and comparable to those reported from a previous study conducted in Japan. Supported by TORG by Taiho Pharmaceutical Co. Ltd under the research contract. Presented in part at the Congress of European Society of Medical Oncology, October 7-11, 2016, Copenhagen, Denmark. S.N., N.I., K.S., H.S., T.K., H.O., T.S., H.K., and M.T. have received honoraria from Taiho Pharmaceutical Co. Ltd. N.I. and T.S. received research funding from Taiho Pharmaceutical Co. Ltd. The other authors declare no conflicts of interest. Reprints: Seiji Niho, MD, PhD, Department of Thoracic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan. E-mail: siniho@east.ncc.go.jp. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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http://ift.tt/2G5jJZG
Emphasis on Systemic Therapy in Women With Pelvic Bone Metastasis at Time of Diagnosis of Cervical Cancer
Objective: Cervical cancer presenting with metastases to the bony pelvis is rare. No available literature addresses the treatment and prognosis of these patients. Our objective was to review our experience treating women with this rare presentation. Methods: We performed a review of all patients treated for cervical cancer at a single institution between January 1, 2007 and November 30, 2014. All patients had pretreatment imaging with computed tomography or positron emission tomography/computed tomography. Included patients had evidence of pelvic bone metastases by imaging before initiation of treatment. Results: A total of 349 women were treated for cervical cancer during the study interval. Of these, 13 (3.7%) were identified as having pelvic bone metastases at initial presentation. Four of 13 patients had pelvic-confined disease and were treated with curative-intent radiation. The remainder had disseminated disease and were treated with palliative radiation. Only one complete response was seen. Seven patients received salvage chemotherapy. The median overall survival was 8.5 months. Survival was statistically similar in those who received palliative rather than curative radiotherapy (8.7 vs. 8.1 mo, P=0.76) and in those who received any postradiation chemotherapy (8.9 vs. 6.1 mo, P=0.066). Chemotherapy with bevacizumab resulted in the only 2 long-term survivors (both alive at 32.4 and 37.5 mo). All others have died of disease. Conclusions: Cervical cancer metastatic to the bony pelvis at initial presentation portends a dismal prognosis. Patients should be informed about this poor prognosis, and allowed to make an informed decision when considering curative-intent versus palliative treatment. Incorporation of bevacizumab appears to improve survival. The authors declare no conflicts of interest. Reprints: Travis T. Sims, MD, 5323 Harry Hines Blvd., Dallas, TX 75390-9032. E-mail: travis.sims@phhs.org. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2DbDL1F
http://ift.tt/2DbDL1F
Preradiotherapy Tumor Volume in Local Control of Squamous Cell Carcinoma of the Supraglottic Larynx
Objectives: Examine the utility of pretreatment computed tomography in predicting local control (LC) in squamous cell carcinoma of the supraglottic larynx treated with primary radiotherapy (RT). Methods: In total, 167 patients treated between 1983 and 2013 were reviewed. Patients had received pretreatment diagnostic computed tomographic imaging of the larynx and neck from which primary tumor volume (PrTV) was delineated. LC, larynx function at last follow-up, and RT complications were recorded. PrTV was evaluated with respect to outcome. Results: In this study, median age was 61 years, and mean follow-up was 96 months. In total, 43% had T1-T2, 46% had T3, and 11% had T4 disease; 49% had N0 disease. Median tumor volume, 5.1 cm3 (0.4 to 188 cm3). Mean dose, 74 Gy; 20% received concurrent chemotherapy. Overall, 10-year LC was 78.9%. Ten-year LC stratified by tumor volume was: 0 to 4.9 cm3, 90.8%; 5 to 8.9 cm3, 67.3%; and >9 cm3, 69.4%. Ten-year LC with preserved larynx function was: 0 to 4.9 cm3, 76.7%; 5 to 8.9 cm3, 61.5%; and >9 cm3, 53.4%. LC and LC with preserved larynx function was significantly different between PrTV groups (P
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Impact of Health Insurance Status on Prostate Cancer Treatment Modality Selection in the United States
Objectives: A variety of treatment modalities are available for the management of clinically localized prostate cancer in the United States. In addition to clinical factors, treatment modality choice may be influenced by a patient's insurance status. Using a national data set, we investigated the relationship between insurance status and prostate cancer treatment modality selection among nonelderly men in the United States. Methods: Nonelderly men age 18 to 64 years treated for localized prostate cancer from 2010 to 2014 were identified within the National Cancer Database. Patients with no insurance, Medicaid, or private insurance were included. The χ2 and multivariable logistic regression analyses were used to evaluate the association of insurance status, other demographic and facility factors, and D'Amico risk classification with treatment modality. Results: We identified 135,937 patients with either no insurance (2.8%), Medicaid (4.2%), or private insurance (92.9%) treated for prostate cancer who underwent cancer-directed treatment or active surveillance between 2010 and 2014. Patients with private insurance were more likely to receive minimally invasive surgery (61.4% vs. 35.4%, respectively; P
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Overall Survival Results of the Feasibility Study of Adjuvant Chemotherapy With Docetaxel Plus Cisplatin Followed by Long-term Single-agent Administration of S-1 in Patients With Completely Resected Non–Small Cell Lung Cancer: Thoracic Oncology Research Group (TORG) 0809
Objectives: The TORG0809 study was a multicenter feasibility study of long-term single-agent therapy with S-1 after docetaxel plus cisplatin therapy in patients with completely resected stage II or stage IIIA non–small cell lung cancer. We report the results of the final overall survival (OS) analysis. Patients and Methods: A total of 129 eligible patients received 3 cycles of docetaxel (60 mg/m2, day 1) plus cisplatin (80 mg/m2, day 1), followed by S-1 at 40 mg/m2 twice daily for 14 consecutive days, for >6 months (maximum, 1 y). Results: At the cutoff date of April 13, 2016, the median follow-up time was 6.0 years. Of the 129 patients, 43 had died, and 74 patients developed disease recurrence or died. The median OS had not been reached. The 5-year OS rate was 71% [95% confidence interval (CI), 62-78]. The 5-year OS rates in the patients with stage II and stage IIIA were 76% and 68%, respectively. The median recurrence-free survival (RFS) duration was 3.4 years (95% CI, 2.3-5.7). The 5-year RFS rate was 44% (95% CI, 36-53). The 5-year RFS rates in patients with stage II and stage IIIA disease were 57% and 38%, respectively. Disease recurrence occurred in 68 patients, and 62 of these patients received second-line chemotherapy. The most common sites of recurrence were the brain (n=22) and mediastinal lymph nodes (n=22). Conclusion: The survival data obtained from this study are promising and comparable to those reported from a previous study conducted in Japan. Supported by TORG by Taiho Pharmaceutical Co. Ltd under the research contract. Presented in part at the Congress of European Society of Medical Oncology, October 7-11, 2016, Copenhagen, Denmark. S.N., N.I., K.S., H.S., T.K., H.O., T.S., H.K., and M.T. have received honoraria from Taiho Pharmaceutical Co. Ltd. N.I. and T.S. received research funding from Taiho Pharmaceutical Co. Ltd. The other authors declare no conflicts of interest. Reprints: Seiji Niho, MD, PhD, Department of Thoracic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan. E-mail: siniho@east.ncc.go.jp. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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Emphasis on Systemic Therapy in Women With Pelvic Bone Metastasis at Time of Diagnosis of Cervical Cancer
Objective: Cervical cancer presenting with metastases to the bony pelvis is rare. No available literature addresses the treatment and prognosis of these patients. Our objective was to review our experience treating women with this rare presentation. Methods: We performed a review of all patients treated for cervical cancer at a single institution between January 1, 2007 and November 30, 2014. All patients had pretreatment imaging with computed tomography or positron emission tomography/computed tomography. Included patients had evidence of pelvic bone metastases by imaging before initiation of treatment. Results: A total of 349 women were treated for cervical cancer during the study interval. Of these, 13 (3.7%) were identified as having pelvic bone metastases at initial presentation. Four of 13 patients had pelvic-confined disease and were treated with curative-intent radiation. The remainder had disseminated disease and were treated with palliative radiation. Only one complete response was seen. Seven patients received salvage chemotherapy. The median overall survival was 8.5 months. Survival was statistically similar in those who received palliative rather than curative radiotherapy (8.7 vs. 8.1 mo, P=0.76) and in those who received any postradiation chemotherapy (8.9 vs. 6.1 mo, P=0.066). Chemotherapy with bevacizumab resulted in the only 2 long-term survivors (both alive at 32.4 and 37.5 mo). All others have died of disease. Conclusions: Cervical cancer metastatic to the bony pelvis at initial presentation portends a dismal prognosis. Patients should be informed about this poor prognosis, and allowed to make an informed decision when considering curative-intent versus palliative treatment. Incorporation of bevacizumab appears to improve survival. The authors declare no conflicts of interest. Reprints: Travis T. Sims, MD, 5323 Harry Hines Blvd., Dallas, TX 75390-9032. E-mail: travis.sims@phhs.org. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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Adjusted calculation model of heparin management during cardiopulmonary bypass in obese patients: A randomised controlled trial
BACKGROUND Anticoagulation during cardiopulmonary bypass (CPB) is usually adapted to total body weight (TBW). This may be inaccurate in obese patients and lead to heparin overdose with a risk of bleeding. OBJECTIVES To validate the efficacy and safety of an adjusted calculation model of heparin dosing based on ideal body weight (IBW) rather than TBW in obese CPB patients, with an expected target mean plasma heparin concentration of 4.5 IU ml−1 after onset of CPB in the experimental group. DESIGN Prospective, randomised controlled study. SETTING University hospital. PATIENTS Sixty obese patients (BMI ≥ 30 kg m−2) scheduled for CPB were included from January to June 2016. INTERVENTIONS Patients received a bolus dose of unfractionated heparin of either 300 IU kg−1 of TBW or 340 IU kg−1 of IBW before onset of CPB. Additional adjusted boluses were injected to maintain an activated clotting time (ACT) of at least 400 s. MAIN OUTCOME MEASURES Plasma heparin concentration and ACT were measured at different time points. Total heparin doses and transfusion requirements were recorded. RESULTS The target heparin concentration of 4.5 IU ml−1 was reached in the IBW group at the onset of CPB and maintained at all time points during CPB. Heparin concentrations were significantly higher in the TBW group after the bolus (6.52 ± 0.97 vs. 4.54 ± 1.13 IU ml−1, P
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Spinal anaesthesia with chloroprocaine 1% versus total intravenous anaesthesia for outpatient knee arthroscopy: A randomised controlled trial
BACKGROUND Both general and spinal anaesthesia with short-acting local anaesthetics are suitable and reliable for knee arthroscopy as an ambulatory procedure. Chloroprocaine (CP) 1% seems to be the ideal spinal local anaesthetic for this indication. OBJECTIVE The aim of this study was to compare spinal anaesthesia using CP 1% with general for outpatient knee arthroscopy with regard to procedure times, occurrence of pain, patient satisfaction and recovery, and also costs. DESIGN A randomised controlled single-centre trial. SETTING University Medical Centre Mannheim, Department of Anaesthesiology and Surgical Intensive Care Medicine, Mannheim, Germany. April 2014 to August 2015. PATIENTS A total of 50 patients (women/men, 18 to 80 years old, ASA I to III) undergoing outpatient knee arthroscopy were included. A contra-indication to an allocated anaesthetic technique or an allergy to medication required in the protocol led to exclusion. INTERVENTIONS Either general anaesthesia with sufentanil, propofol and a laryngeal mask for airway-management or spinal with 40-mg CP 1% were used. We noted procedure times, patient satisfaction/recovery and conducted a 7-day follow-up. MAIN OUTOMES Primary outcome was duration of stay in the day-surgery centre. Secondary outcomes were first occurrence of pain, patient satisfaction, quality of recovery and adverse effects. In addition, we analysed treatment costs. RESULTS Spinal had faster recovery than general anaesthesia with patients reaching discharge criteria significantly earlier [117 min (66 to 167) versus 142 min (82 to 228), P = 0.0047]. Pain occurred significantly earlier in the general anaesthesia group (P = 0.0072). Costs were less with spinal anaesthesia (cost ratio spinal: general 0.57). Patients felt significantly more uncomfortable after general anaesthesia (P = 0.0096). CONCLUSION Spinal anaesthesia with 40-mg CP 1% leads to a significantly earlier discharge and is cheaper compared with general. TRIAL REGISTRATION German Clinical Trials Register, www.drks.de, identifier: DRKS00005989. Correspondence to Prof. Dr. med. Marc D. Schmittner, Head, Department of Anaesthesiology, Intensive Care and Pain Medicine, BG Klinikum Unfallkrankenhaus Berlin gGmbH, Warener Str. 7, 12683 Berlin, Germany Tel: +49 (0) 30 56 81 3100; fax: +49 (0) 30 56 81 3103; e-mail: marc.schmittner@ukb.de © 2018 European Society of Anaesthesiology
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Cancer immunotherapy in patients with brain metastases
Abstract
The exclusion of "real-world" patients from registration clinical trials of cancer immunotherapy represents a significant emerging issue. For instance, a large fraction of cancer patients develops brain metastases during the course of the disease, but results from large prospective clinical trials investigating this considerable proportion of the cancer patient population are currently lacking. To provide a useful tool for the clinician in a "real-world" setting, we have reviewed the available literature regarding the safety and efficacy of immune check-point inhibitors in patients with cancer metastatic to the brain. Overall, these data provide encouraging evidence that these therapeutic agents can induce intracranial objective responses, particularly in patients with asymptomatic and previously untreated brain metastases. Larger prospective studies are needed to confirm these initial results.
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Cancer immunotherapy in patients with brain metastases
Abstract
The exclusion of "real-world" patients from registration clinical trials of cancer immunotherapy represents a significant emerging issue. For instance, a large fraction of cancer patients develops brain metastases during the course of the disease, but results from large prospective clinical trials investigating this considerable proportion of the cancer patient population are currently lacking. To provide a useful tool for the clinician in a "real-world" setting, we have reviewed the available literature regarding the safety and efficacy of immune check-point inhibitors in patients with cancer metastatic to the brain. Overall, these data provide encouraging evidence that these therapeutic agents can induce intracranial objective responses, particularly in patients with asymptomatic and previously untreated brain metastases. Larger prospective studies are needed to confirm these initial results.
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Cancer immunotherapy in patients with brain metastases
Abstract
The exclusion of "real-world" patients from registration clinical trials of cancer immunotherapy represents a significant emerging issue. For instance, a large fraction of cancer patients develops brain metastases during the course of the disease, but results from large prospective clinical trials investigating this considerable proportion of the cancer patient population are currently lacking. To provide a useful tool for the clinician in a "real-world" setting, we have reviewed the available literature regarding the safety and efficacy of immune check-point inhibitors in patients with cancer metastatic to the brain. Overall, these data provide encouraging evidence that these therapeutic agents can induce intracranial objective responses, particularly in patients with asymptomatic and previously untreated brain metastases. Larger prospective studies are needed to confirm these initial results.
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Diagnostic Model of Serum miR-193a-5p, HE4 and CA125 Improves the Diagnostic Efficacy of Epithelium Ovarian Cancer
Abstract
Epithelium ovarian cancer (EOC) is currently the prevalent malignant cancer worldwide. However, there is a lack of efficient biomarkers for EOC screening. Accumulating evidence reveals that serum miRNA detectable in various types of cancer. Therefore, we explore the diagnostic value of combined detection of plasma miR-193a-5p, HE4 and CA125 for EOC. Serum samples were collected from 45 patients with primary EOC, 30 patients with benign ovarian tumor patients and 40 healthy controls. The expression of serum miR-193a-5p was detected by real-time quantitative PCR, and serum HE4 and CA125 were detected by chemiluminescent immunoassay. Moreover, a diagnostic model combining miR-193a-5p, HE4 and CA125 or alone in EOC patients was evaluated by ROC curve analysis. The relative expression quantity (RQ) of serum miR-193a-5p in EOC patients, benign ovarian tumor patients and healthy control groups were 0.419 (0.093, 2.215), 3.667 (1.633, 6.691) and 1.130 (1.000, 7.087), respectively. The RQ of serum miR-193a-5p in EOC patients was significantly lower than that in benign ovarian tumor patients and healthy controls (both P < 0.001), and there was no significant difference between benign ovarian tumor patients and healthy controls (both P > 0.05). There was no significant correlation between serum miR-193-5p, HE4 and CA125 levels (both P > 0.05). Additionally a risk model for miR-193a-5p, HE4 and CA125 was correlated with Grading and Lymph node metastasis (P = 0.016, P = 0.029). The area under the receiver operating characteristic curve of a risk model for distinguishing EOC patients from healthy individuals was 0.996, which higher than any single biomarker. Combined detection of miR-193-5p, HE4 and CA125 by logistic regression analysis could greatly improved the diagnostic ability of EOC and may prove to be a candidate biomarker, providing new directions for further investigation.
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Postoperative cesarean pain: real but is it preventable?
Purpose of review Cesarean section is the most common surgical procedure performed in the world. Postoperative pain management remains a challenge, particularly in a context of enhanced recovery after surgery. Several barriers related to the specific condition of 'postpartum recovery' may prevent application of effective analgesia in this population. The present review focuses on novel approaches of cesarean section postoperative pain assessment, beyond pain-rating intensity, including objective patient-centered recovery parameters. Predictive tools currently available to target patients at high risk of acute and chronic pain are also examined. Recent findings Postoperative pain after cesarean section is more severe than reported in the majority of randomized control trials. Pain seriously interferes with early and also late functional recovery, although Enhanced Recovery after Surgery (ERAS) programmes are being promoted. Pain-rating scores can differ from scores of physical comfort and physical independence, which are priorities for postpartum patients. Further, the value of subjective pain intensity rating to adapt analgesic prescription is misleading and may promote opioid over-prescription. Available tools to predict at-risk patients for severe pain after cesarean section are not easy to use in daily clinical practice and have, at best, moderate predictive value. Summary Patient and healthcare provider education on reported pain and well tolerated analgesic use is the key to improve postpartum pain management after cesarean section. Correspondence to Patricia Lavand'homme, MD, PhD, Department of Anesthesiology, Cliniques Universitaires St Luc - University Catholic of Louvain, Av Hippocrate 10, B-1200 Brussels, Belgium. Tel: +32 2 764 18 21; fax: +32 2 764 36 99; e-mail: patricia.lavandhomme@uclouvain.be Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.
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Dose-dense weekly chemotherapy in advanced ovarian cancer: An updated meta-analysis of randomized controlled trials
Publication date: Available online 7 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): C. Marchetti, F. De Felice, A. Di Pinto, O. D'Oria, N. Aleska, A. Musella, I. Palaia, L. Muzii, V. Tombolini, P. Benedetti Panici
ObjectiveThe use of dose-dense weekly chemotherapy in the management of advanced ovarian cancer (OC) remains controversial. The aim of this meta-analysis was to evaluate the efficacy of dose-dense regimen to improve clinical outcomes in OC patients with the inclusion of new trials.MethodsFor this updated meta-analysis, PubMed Medline and Scopus databases and meeting proceedings were searched for eligible studies with the limitation of randomized controlled trials, comparing dose-dense chemotherapy versus standard treatment. Trials were grouped in two types of dose-dense chemotherapy: weekly dose-dense (both paclitaxel and carboplatin weekly administration) and semi-weekly dose-dense (weekly paclitaxel and three weekly carboplatin administration). Data were extracted independently and were analyzed using RevMan statistical software version 5.3 (http://www.cochrane.org). Primary end-point was progression-free survival (PFS).ResultsFour randomized controlled trials comprising 3,698 patients were identified as eligible. Dose-dense chemotherapy had not a significant benefit on PFS (HR 0.92, 95% CI 0.81–1.04, p = 0.20). When the analysis was restricted to both weekly and semi-weekly dose-dense data, a no significant interaction between dose-dense and standard regimen was confirmed (HR 1.01, 95% CI 0.93–1.10 and HR 0.82, 95% CI 0.63–1.08, respectively).ConclusionsIn the absence of PFS superiority of dose-dense schedule, three weekly schedule should remain the standard of care for advanced OC.
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Circulating Tumor Cells Count as a Predictor of Survival in Lung Cancer
Publication date: Available online 7 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Konstantinos Syrigos, Oraianthi Fiste, Andriani Charpidou, Dimitra Grapsa
The presence of circulating tumor cells (CTCs) in the peripheral blood of cancer patients was first described in the second half of the 19th century, but research interest in their potential clinical utility has intensified and greatly expanded only in recent years. Herein, we summarize and critically discuss current knowledge on CTC count as a predictor of survival in lung cancer, and comment on the existing challenges and future perspectives in this field. The majority of data published to date, including the results of almost all large cohorts, are strongly supportive of the value of CTC enumeration as a predictor of survival, mainly in advanced/metastatic non-small and small cell lung cancer (NSCLC and SCLC, respectively). Nonetheless, additional research is warranted to establish the prognostic relevance of CTC count in other clinical settings, mainly encompassing earlier-stage disease as well as specific molecular subtypes of NSCLC (e.g. EGFR mutation-positive or ALK-positive cases).
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Treatment of Spinal Metastases in Renal Cell Carcinoma: A Critical Review
Publication date: Available online 6 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Diego Teyssonneau, Marine Gross-Goupil, Charlotte Domblides, Thibaud Haaser, Vincent Pointillart, Amaury Daste, Olivier Hauger, Alain Ravaud
Kidney cancer is the 9th most common cancer in men and the 14th most common in women worldwide. Renal cell carcinoma (RCC) constitutes 90% of all malignancies of the kidney. RCC, is known to be highly vascular and relatively radioresistant. Bone metastases are one of the most common metastatic sites and occur in around 30% of RCCs. They significantly impact the quality of life of patients causing pain and pathological fractures. Spinal metastases represent a particular case with regard to symptoms and treatment. Indeed, neurological pain is often added to the nociceptive pain caused by metastases. More importantly, neurological impairment can be seen, caused by spinal cord or nerve root compression (MSCC). Due to close contact with the spinal cord, the treatment of spinal bone metastases is challenging and requires a multidisciplinary approach.Specific treatment is currently focused on 4 main avenues which are surgery, radiotherapy, interventional radiology and systemic treatment.In June 2017 we carried out an extensive search on PubMed, Web of Science, and Cochrane Library to review the various treatment options and to establish a treatment strategy.This article presents the result of our critical review of the literature, given our expertise in the field.
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Dose-dense weekly chemotherapy in advanced ovarian cancer: An updated meta-analysis of randomized controlled trials
Publication date: Available online 7 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): C. Marchetti, F. De Felice, A. Di Pinto, O. D'Oria, N. Aleska, A. Musella, I. Palaia, L. Muzii, V. Tombolini, P. Benedetti Panici
ObjectiveThe use of dose-dense weekly chemotherapy in the management of advanced ovarian cancer (OC) remains controversial. The aim of this meta-analysis was to evaluate the efficacy of dose-dense regimen to improve clinical outcomes in OC patients with the inclusion of new trials.MethodsFor this updated meta-analysis, PubMed Medline and Scopus databases and meeting proceedings were searched for eligible studies with the limitation of randomized controlled trials, comparing dose-dense chemotherapy versus standard treatment. Trials were grouped in two types of dose-dense chemotherapy: weekly dose-dense (both paclitaxel and carboplatin weekly administration) and semi-weekly dose-dense (weekly paclitaxel and three weekly carboplatin administration). Data were extracted independently and were analyzed using RevMan statistical software version 5.3 (http://www.cochrane.org). Primary end-point was progression-free survival (PFS).ResultsFour randomized controlled trials comprising 3,698 patients were identified as eligible. Dose-dense chemotherapy had not a significant benefit on PFS (HR 0.92, 95% CI 0.81–1.04, p = 0.20). When the analysis was restricted to both weekly and semi-weekly dose-dense data, a no significant interaction between dose-dense and standard regimen was confirmed (HR 1.01, 95% CI 0.93–1.10 and HR 0.82, 95% CI 0.63–1.08, respectively).ConclusionsIn the absence of PFS superiority of dose-dense schedule, three weekly schedule should remain the standard of care for advanced OC.
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Circulating Tumor Cells Count as a Predictor of Survival in Lung Cancer
Publication date: Available online 7 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Konstantinos Syrigos, Oraianthi Fiste, Andriani Charpidou, Dimitra Grapsa
The presence of circulating tumor cells (CTCs) in the peripheral blood of cancer patients was first described in the second half of the 19th century, but research interest in their potential clinical utility has intensified and greatly expanded only in recent years. Herein, we summarize and critically discuss current knowledge on CTC count as a predictor of survival in lung cancer, and comment on the existing challenges and future perspectives in this field. The majority of data published to date, including the results of almost all large cohorts, are strongly supportive of the value of CTC enumeration as a predictor of survival, mainly in advanced/metastatic non-small and small cell lung cancer (NSCLC and SCLC, respectively). Nonetheless, additional research is warranted to establish the prognostic relevance of CTC count in other clinical settings, mainly encompassing earlier-stage disease as well as specific molecular subtypes of NSCLC (e.g. EGFR mutation-positive or ALK-positive cases).
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Treatment of Spinal Metastases in Renal Cell Carcinoma: A Critical Review
Publication date: Available online 6 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Diego Teyssonneau, Marine Gross-Goupil, Charlotte Domblides, Thibaud Haaser, Vincent Pointillart, Amaury Daste, Olivier Hauger, Alain Ravaud
Kidney cancer is the 9th most common cancer in men and the 14th most common in women worldwide. Renal cell carcinoma (RCC) constitutes 90% of all malignancies of the kidney. RCC, is known to be highly vascular and relatively radioresistant. Bone metastases are one of the most common metastatic sites and occur in around 30% of RCCs. They significantly impact the quality of life of patients causing pain and pathological fractures. Spinal metastases represent a particular case with regard to symptoms and treatment. Indeed, neurological pain is often added to the nociceptive pain caused by metastases. More importantly, neurological impairment can be seen, caused by spinal cord or nerve root compression (MSCC). Due to close contact with the spinal cord, the treatment of spinal bone metastases is challenging and requires a multidisciplinary approach.Specific treatment is currently focused on 4 main avenues which are surgery, radiotherapy, interventional radiology and systemic treatment.In June 2017 we carried out an extensive search on PubMed, Web of Science, and Cochrane Library to review the various treatment options and to establish a treatment strategy.This article presents the result of our critical review of the literature, given our expertise in the field.
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JAMA Oncology Peer Reviewers in 2017
We sincerely thank the 876 peer reviewers who completed manuscript reviews for JAMA Oncology in 2017.
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Pacritinib vs Best Available Therapy in Patients With Myelofibrosis
This phase 3 randomized clinical trial compares the efficacy and safety of Janus kinase 2 inhibitor pacritinib with that of best available therapy, including ruxolitinib, in patients with myelofibrosis and thrombocytopenia.
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Possible Underestimation of the Provision of Palliative Care
To the Editor In their Viewpoint, Schenker and Arnold reflect about the currently published American Society of Clinical Oncology (ASCO) guideline that recommends that all patients with advanced cancer should receive palliative care. In doing this, they plead for a public health approach (instead of palliative care by palliative care specialists only) of providing palliative care as a core component of the health care system. We also believe that such an approach is the right way to go. Yet, we also believe that this Viewpoint neglects some important aspects that need to be explored beforehand, for example, whether and when patients in fact receive inadequate palliative care.
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Radiographic Progression-Free Survival as End Point in Prostate Cancer
This phase 3 randomized clinical trial uses prespecified sensitivity analyses from 1717 men with chemotherapy-naive metastatic castration-resistant prostate cancer to assess the clinical relevance of the Prostate Cancer Working Group 2 definition of radiographic progression-free survival.
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Possible Underestimation of the Provision of Palliative Care—Reply
In Reply We agree with Buiting and de Graas that not all provision of palliative care is labeled as palliative care and that many oncology clinicians provide palliative care beautifully without calling it such. Traditionally, alleviating suffering in serious illness was simply called good medical care. We agree with that view. To the degree to which core palliative care domains (eg, symptom management, good communication) are viewed as a specialty task, rather than a part of good clinical care, this is a problem.
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Refusing to Become a “Potted Plant”
This article describes the experience of a physician in the Netherlands who has performed euthanasia at the request of a patient.
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FDA Approval of Adjuvant Sunitinib for Renal Cell Cancer
This Viewpoint examines the data and circumstances behind the US Food and Drug Administration approval of sunitinib as adjuvant treatment for patients with resected renal cell carcinoma who are at a high risk of relapse.
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JAMA Oncology —The Year in Review, 2017
This has been a terrific year for JAMA Oncology. Our debut impact factor of 16.56 placed us as one of the highest-ranking oncology journals. JAMA Oncology published 30 of the top 50 papers among oncology journals as measured by Altmetric. We would like to thank our authors, reviewers, and readers for the significant contributions made to the journal this past year. The editorial board and I are honored to have the opportunity to serve the oncology community by offering original, innovative, and timely scientific content that has a direct impact on researchers, clinicians, and the patients we serve.
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Carfilzomib-Associated Cardiovascular Adverse Events
This systematic review with meta-analysis examines the rates of cardiovascular adverse events among patients receiving carfilzomib for the treatment of multiple myeloma.
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Alterations in Main Driver Genes in Patients With Pancreatic Adenocarcinoma
This study examines the protein expression and DNA alteration for the KRAS, CDKN2A, SMAD4, and TP53 main driver genes to determine their association with patient outcomes after pancreatic cancer surgical resection.
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Patient Portal Use in Oncology Practice
This study examines the association of accessing electronic oncology patient portal data with patient characteristics and type of portal content.
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Taxane Followed by Anthracycline or Vice Versa—Reply
In Reply Dr Altundag suggests that giving a taxane first followed by an anthracycline, as was done in the FinXX trial, might be beneficial to patients who also receive capecitabine in the adjuvant setting. In the FinXX trial, the patients were randomly allocated to either 3 cycles of docetaxel followed by 3 cycles of cyclophosphamide, epirubicin, and fluorouracil or to 3 cycles of docetaxel plus capecitabine followed by 3 cycles of cyclophosphamide, epirubicin, and capecitabine. Therefore, the patients who participated in this trial received a taxane (docetaxel) first, followed by an anthracycline (epirubicin).
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Costs of Medical Education and Oncology Workforce Diversity
This Viewpoint examines the financial burden of medical school for aspiring oncologists from underrepresented backgrounds and suggests potential programs to help alleviate the financial burden.
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Not Just Digital Pathology, Intelligent Digital Pathology
This commentary discusses a study in JAMA that compared the ability of machine learning algorithms vs clinical pathologists to detect cancer metastases in whole-slide images of axillary lymph nodes dissected from women with breast cancer.
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The Danger of Applying the ProtecT Trial to Minority Populations
This Viewpoint examines the generalizability of the results of ProtecT Trial to minority populations.
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All Thiopurines Are Equal But Some Thiopurines Are More Equal—Reply
In Reply Meijer and de Boer offer a valid examination of our study conclusions for azathioprine sodium association with therapy-related myeloid neoplasm that excludes mention of 6-mercaptopurine. As highlighted in our article's Limitations section, small sample size, particularly for individual drug classification, limits interpretation, because many of these comparisons are underpowered, resulting in nonsignificant odds ratios and associated wide confidence intervals. Notably, only 12 patients received mercaptopurine in our study of 86 patients (3 cases and 9 controls), resulting odds ratio, 0.62 (95% CI, 0.15-2.53), thus statistically nonsignificant at P = .51. Indeed, a multivariate model was constructed in which agents with P < .20 were included and only azathioprine remained significant (odds ratio, 6.92; 95% CI, 2.21-21.66) when controlling for cyclophosphamide, methotrexate sodium, and leflunomide use. To elucidate further questions on nonsignificant results from our study requires a larger sample size or prospective investigations.
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History of Lymphoma
"History of lymphoma." I hate those words. Not because I had lymphoma. I actually had AML (acute myeloid leukemia) and a stem-cell transplant, and thank you, that was enough for me. I hate those words because that is the sum total of what is mentioned in the medical history of far too many primary care physicians' (PCPs) medical records for childhood and adult lymphoma survivors. You could substitute breast cancer, lung cancer, colon cancer, or any other malignancy, and you will find the same lack of information.
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Faith Healer
I went to the faith healertoday to cure my cancerthinking that perhaps it wasmy lack of faith that had caused itin the first place.
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Treating ERBB2/HER-2 –Negative Breast Cancer With Nab-paclitaxel
This randomized clinical trial determines whether nab-paclitaxel improves the outcomes of early and locally advanced ERBB2/HER2-negative breast cancer compared with paclitaxel when delivered in a neoadjuvant setting.
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miR-181a targets GATA6 to inhibit the progression of human laryngeal squamous cell carcinoma
Future Oncology, Ahead of Print.
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YB-1 promotes laryngeal squamous cell carcinoma progression by inducing miR-155 expression via c-Myb
Future Oncology, Ahead of Print.
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Thermal ablation versus surgical resection for localized hepatocellular carcinoma: a population study using the SEER database
Future Oncology, Ahead of Print.
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miR-181a targets GATA6 to inhibit the progression of human laryngeal squamous cell carcinoma
Future Oncology, Ahead of Print.
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YB-1 promotes laryngeal squamous cell carcinoma progression by inducing miR-155 expression via c-Myb
Future Oncology, Ahead of Print.
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Thermal ablation versus surgical resection for localized hepatocellular carcinoma: a population study using the SEER database
Future Oncology, Ahead of Print.
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Characterization of metastatic urothelial carcinoma via comprehensive genomic profiling of circulating tumor DNA
BACKGROUND
Biomarker-guided clinical trials are increasingly common in metastatic urothelial carcinoma (mUC), yet patients for whom contemporary tumor tissue is not available are not eligible. Technological advancements in sequencing have made cell-free circulating DNA (cfDNA) next-generation sequencing (NGS) readily available in the clinic. The objective of the current study was to determine whether the genomic profile of mUC detected by NGS of cfDNA is similar to historical tumor tissue NGS studies. A secondary objective was to determine whether the frequency of genomic alterations (GAs) differed between lower tract mUC (mLTUC) and upper tract mUC (mUTUC).
METHODS
Patients from 13 academic medical centers in the United States who had a diagnosis of mUC between 2014 and 2017 and for whom cfDNA NGS results were available were included. cfDNA profiling was performed using a commercially available platform (Guardant360) targeting 73 genes.
RESULTS
Of 369 patients with mUC, 294 were diagnosed with mLTUC and 75 with mUTUC. A total of 2130 GAs were identified in the overall mUC cohort: 1610 and 520, respectively, in the mLTUC and mUTUC cohorts. In the mLTUC cohort, frequently observed GAs were similar between cfDNA NGS and historical tumor tissue studies, including tumor protein p53 (TP53) (P = 1.000 and .115, respectively), AT-rich interaction domain 1A (ARID1A) (P = .058 and .058, respectively), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) (P = .058 and .067, respectively), erb-b2 receptor tyrosine kinase 2 (ERBB2) (P = .565 and .074, respectively), and fibroblast growth factor receptor 3 (FGFR3) (P = .164 and .014, respectively). No significant difference was observed with regard to the frequency of GAs between patients with mLTUC and mUTUC.
CONCLUSIONS
Among patients with mUC for whom no tumor tissue was available, cfDNA NGS was able to identify a similar profile of GAs for biomarker-driven clinical trials compared with tumor tissue. Despite the more aggressive clinical course, cases of mUTUC demonstrated a circulating tumor DNA genomic landscape that was similar to that of mLTUC. Cancer 2018. © 2018 American Cancer Society.
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