Current status of ramucirumab in gastroesophageal adenocarcinoma

Future Oncology Ahead of Print.


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Current status of ramucirumab in gastroesophageal adenocarcinoma

Future Oncology Ahead of Print.


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A pseudotumour of the thigh: tensor fasciae latae muscle hypertrophy due to an underlying abductor tendon tear

We present a patient with an asymptomatic unilateral swelling of the anterolateral thigh. MRI showed hypertrophy of the tensor fasciae latae muscle due to an underlying gluteus minimus tendon tear.

Abductor tendon tears can present with swelling of the thigh due to secondary tensor fasciae latae muscle hypertrophy.

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Current status of ramucirumab in gastroesophageal adenocarcinoma

Future Oncology Ahead of Print.


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PARP Inhibitors May Be Effective in Brain, Other Cancers with IDH Mutations

Studies presented at the 2017 AACR annual meeting suggest that therapies which take advantage of the mutations in the IDH gene may be more effective than drugs that block it.

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Hypofractionated short-course radiotherapy in elderly patients with glioblastoma multiforme: an analysis of the National Cancer Database

Abstract

For elderly patients with glioblastoma multiforme (GBM), randomized trials have shown similar survival with hypofractionated short-course radiotherapy (SCRT) compared to conventionally fractionated long-course radiotherapy (LCRT). We evaluated the adoption of SCRT along with associated factors and survival in a national patient registry. Using the National Cancer Data Base (NCDB), we identified patients aged ≥70 years with GBM, diagnosed between 1998 and 2011, who received SCRT (34–42 Gy in 2.5–3.4 Gy fractions), or LCRT (58–63 Gy in 1.8–2.0 Gy fractions). Crude and adjusted hazard ratios (HR) were calculated using Cox regression modeling. 4598 patients were identified, 304 (6.6%) in the SCRT group and 4294 (93.4%) in the LCRT group. Median follow-up was 8.4 months. Median age was 78 versus 75 years, respectively (P < 0.0001). Patients who received SCRT had higher Charlson–Deyo comorbidity scores versus LCRT (score of ≥2: 16.9% vs. 10.8%, respectively; P = 0.006), and were more likely to be female (53.0% vs. 44.6%, P = 0.005). Patients who received SCRT were less likely to undergo chemotherapy (42.8% vs. 79.3%, P < 0.0001), more likely to undergo biopsy only (34.5% vs. 19.5%, P < 0.0001), and more likely to receive treatment at academic/research programs (49.2% vs. 37.2%, P = 0.0001). Median survival was 4.9 months versus 8.9 months, respectively (P < 0.0001). The survival detriment with SCRT persisted on multivariable analysis [HR 1.51 (95% CI: 1.33–1.73, P < 0.0001)], adjusting for age, gender, race, comorbidities, diagnosis year, facility type, surgery, and chemotherapy. In conclusion, hypofractionated SCRT was associated with worse survival compared to conventionally fractionated LCRT for elderly patients with GBM. Patients who received SCRT were older with worse comorbidities, and were less likely to undergo chemotherapy or resection.

In this analysis of elderly patients with glioblastoma multiforme registered in the National Cancer Data Base, hypofractionated short-course radiotherapy was associated with worse survival compared to conventionally fractionated long-course radiotherapy. Patients who received short-course radiotherapy were older, had more comorbidities, and were less likely to undergo chemotherapy or tumor resection.

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Elevated glypican-1 expression is associated with an unfavorable prognosis in pancreatic ductal adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer in humans, with a 5-year survival rate of <5%. Recently, glypican-1 (GPC1)-expressing circulating exosomes were found to be a promising diagnostic tool for PDAC. However, the aberrant expression of GPC1 has not been systematically evaluated in large-scale clinical samples of PDAC. Here, we performed a comprehensive analysis of GPC1 mRNA and protein expression features. Included in this study were 178 PDAC patients from the cancer genome atlas (TCGA) and 186 subjects whose tissues were used in immunohistochemical staining assays. We demonstrated that GPC1 mRNA was silenced in normal pancreata; however, it was re-expressed in PDAC tissues probably because of the promoter hypomethylation. The GPC1 protein was barely expressed in the normal and adjacent noncancerous pancreata. In tumor tissues, 59.7% (111/186) of the detected samples showed positive expression. Notably, GPC1 was elevated in 63.6% (34/55) of early stage cases. High levels of GPC1 were associated with poorer differentiation and larger tumor diameters. Kaplan–Meier analysis showed a significant difference in overall survival between the groups categorized by GPC1 expression (P = 0.0028). Multivariate analyses indicated that GPC1 was a significant risk factor for poor overall survival with a 1.82-fold increase in the hazard ratio (P = 0.0022). In conclusion, during pancreatic tumorigenesis, GPC1 was ectopically expressed and served as an independent poor prognostic factor. Our findings highlighted the alluring prospect of GPC1 as an early diagnostic and prognostic marker as well as a therapeutic target for PDAC.

GPC1 protein expression was associated with poor prognosis in PDAC.

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MiR-145 inhibits human colorectal cancer cell migration and invasion via PAK4-dependent pathway

Abstract

MicroRNA-145 (miR-145), as a tumor-suppressive miRNA, has been demonstrated down-regulated in colorectal cancer (CRC) cells, and could inhibit CRC cells growth. However, the molecular pathway in which miR-145 modulates CRC malignant transformation has not been fully revealed. Here, we reported an intense correlation between the expressions of PAK4 and miR-145 in human CRC cell lines. Transwell assay verified overexpression of miR-145, as well as knockdown of PAK4, significantly suppressed cell migration and invasion ability. The impaired migration and invasion ability of SW1116 cells was affected through the down-regulation of phosphorylation level of LIMK1 and cofilin in a PAK4-dependent manner. Collectively, we have demonstrated that miR-145 suppressed CRC migration and invasion through PAK4 pathway, which provides an attractive microRNA-based therapeutic target for CRC.

The molecular mechanism by which miR-145, a tumor-suppressive miRNA, modulates colorectal cancer cells malignant transformation has been revealed in this manuscript.

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Overcoming Linsitinib intrinsic resistance through inhibition of nuclear factor-κB signaling in esophageal squamous cell carcinoma

Abstract

The aim of this study is to evaluate the efficacy of insulin-like growth factor 1 receptor (IGF-1R) inhibitor Linsitinib, in esophageal squamous cell carcinoma (ESCC), and to characterize special biomarker to screen Linsitinib-sensitive patients as well as explore the molecular-resistant mechanism to Linsitinib in ESCC. Our study evaluated the sensitivity of insulin-like growth factor 1 receptor (IGF-1R) inhibitor, Linsitinib in ESCC cells with MTT assay. After Linsitinib treatment, the expressions of downstream signaling molecules and apoptosis pathways were measured by western blot. And the antitumor effect of Linsitinib and JSH-23, an inhibitor of nuclear factor-κB transcriptional activity, was analyzed both as single agent and in combination in ESCC. Apoptosis, cell viability, and clonogenic survival analysis were also investigated. The sensitivity of Linsitinib was relatively variable in patient-derived primary ESCC cells as well as in human commercial cell lines. And the downstream AKT/mTOR and ERK signaling pathways were inhibited by Linsitinib, while phosphorylation level of NF-κB p65 was obviously activated to reduce apoptosis effect in Linsitinib-resistant cell lines. Most importantly, blockage of NF-κB activity by JSH-23 could sensitize resistant cells to Linsitinib treatment. Results from this study demonstrated that the intrinsic resistance to Linsitinib was predominantly mediated by NF-κB activation in ESCC. Moreover, combination of Linsitinib and JSH-23 as therapy provides a novel strategy to overcome resistance to Linsitinib in ESCC.

The intrinsic resistance of esophageal squamous cell carcinoma (ESCC) to Linsitinib may be mediated by NF-κB activation. A combined therapy that targets both IGF-1R and NF-κB provides a novel strategy to overcome resistance to Linsitinib in ESCC.

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MiR-372-3p promotes cell growth and metastasis by targeting FGF9 in lung squamous cell carcinoma

Abstract

The aim of this study was to study the role of miR-372-3p in lung squamous cell carcinoma (LSCC) cell proliferation and invasion by suppressing FGF9. RT-PCR was used to determine miR-372-3p and FGF9 mRNA expression in tissues and cells. Western blot was used to determine FGF9 expression in tissues and NCI-H520 cell line. Dual luciferase reporter gene assay was conducted to confirm that FGF9 can be directly targeted by miR-372-3p. MTT, colony formation assays were conducted to investigate the effects of ectopic miR-372-3p and FGF9 expression on NCI-H520 cell growth. Flow cytometry was used to analyze the influence of miR-372-3p and FGF9 expression on cell cycle distribution and apoptosis. Transwell assay was also conducted to see the effects of miR-372-3p and FGF9 expression on NCI-H520 cell invasiveness. MiR-372-3p was found significantly overexpressed in both LSCC tissues and cell lines, whereas FGF9 mRNA was found underexpressed in LSCC tissues. MiR-372-3p directly bound to wild-type FGF9 mRNA 3′UTR, therefore led to the reduction in FGF9 expression. The upregulation of FGF9 or the downregulation of miR-372-3p substantially retarded LSCC cell growth, mitosis, and invasion. MiR-372-3p enhanced LSCC cell proliferation and invasion through inhibiting FGF9.

MiR-372-3p enhanced LSCC cell proliferation and invasion through inhibiting FGF9.

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miR-148b inhibits glycolysis in gastric cancer through targeting SLC2A1

Abstract

Although the molecular biology of GC has been well characterized, early diagnostic biomarkers and effective therapeutic options in gastric cancer are still under investigation. Here, we found that miR-148b expression decreased in human gastric cancer tissues compared with matched adjacent nontumor tissues by q-PCR analysis and in situ hybridization. Further investigation revealed that overexpression of miR-148b limited glycolysis including glucose consumption, lactate production in gastric cancer cell lines BGC-823 and MKN45. Bioinformatics prediction uncovered that a dedicated transporters solute carrier family 2 member 1 (SLC2A1), also called GLUT1, was the direct target of miR-148b. The target effects were further confirmed by luciferase assay and western blot analysis. Besides, a reverse correlation was observed between relative SLC2A1 and miR-148b expression in human GC tissues compared with matched adjacent nontumor tissues. Subsequently, SLC2A1 suppression by SLC2A1 siRNA or specific inhibitor restricted the reduced effects of glycolysis mediated by miR-148b while SLC2A1 overexpression abrogated the effect of miR-148b on glycolysis. Our findings provided new evidence of miR-148b in GC development through restraining glycolysis, highlighting the role of miR-148b as a new target for GC treatment.

miR-148b inhibits GC development through restraining glycolysis, highlighting the role of miR-148b as a new target for GC treatment.

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CKS1BP7, a Pseudogene of CKS1B, is Co-Amplified with IGF1R in Breast Cancers

Abstract

Pseudogenes have been reported to exhibit functional roles. Amplification or overexpression of CDC28 protein kinase regulatory subunit 1B (CKS1B) was found in various human cancers. But it was known little about CKS1B pseudogene 7 (CKS1BP7), a pseudogene sharing considerable sequence identity with CKS1B. The aim of this study was to evaluate copy number alterations (CNAs) of CKS1BP7 and address its potential roles in breast cancer. We detected copy numbers of CKS1BP7 and insulin-like growth factor 1 receptor (IGF1R) using quantitative multi-gene fluorescence in situ hybridization (QM-FISH) technique, compared their status in both invasive carcinoma and ductal carcinoma in situ (DCIS) components within the same tumors, and investigated the associations of CNAs with tumor features and patients outcomes. Amplification of CKS1BP7 (dot-like pattern) was found in 28.8% of all cases, while amplified IGF1R (cluster pattern) was identified in 24.2% of all patients. The two events often co-existed (p = 0.01). Within the same tumors, identical CNAs of CKS1BP7 and IGF1R were found in DCIS and invasive carcinoma. Moreover, amplification of both genes was more frequent in aneuploidy tumors and the tumors with high ki67, but wasn't associated with patients' outcome. In summary, CKS1BP7 amplification is a frequent event in breast cancer and often co-occurs with amplified IGF1R, which provides evidence supporting the interactions between CKS1BP7 and IGF1R during mammary carcinogenesis. Our findings suggest that CKS1BP7 as well as IGF1R may serve as potential biomarkers for early detection and predict prognosis in breast cancer.

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Prognostic relevance of miR-124-3p and its target TP53INP1 in pediatric ependymoma

Abstract

Ependymoma is a malignant pediatric brain tumor, often incurable under the current treatment regimen. We aimed to evaluate the expression of microRNAs (miRs) in pediatric ependymoma tumors in an attempt to identify prognostic molecular markers which would lead to potential therapeutic targets. Following miR-array expression analysis, we focused on 9 miRs that correlated with relapse which were further validated by quantitative real time PCR (qRT-PCR) in a cohort of 67 patients. Western blotting and immunohistochemistry were used to measure target protein expression in 20 and 34 tumor samples, respectively. High expression of miR-124-3p significantly correlated with the lower progression-free survival (PFS) of 16% compared to 67% in those expressing low levels (p=0.002). Interestingly, in the group of patients with local disease (n=56) expression levels of this miR distinguished 2 subgroups with a significantly different outcome (p=0.001). miR-124-3p was identified as an independent prognostic factor of relapse in the multivariate analysis performed in the whole cohort and in the group with localized disease. In the localized group, a patient expressing high levels of miR-124-3p had a 4.1-fold increased risk for relapse (p=0.005). We demonstrated the direct binding of miR-124-3p to its target TP53INP1. Negative TP53INP1 protein levels correlated with a poor outcome (p=0.034). We propose miR-124-3p and TP53INP1 as new biomarkers for prognostic stratification that may be possible therapeutic targets for ependymoma. This article is protected by copyright. All rights reserved.

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A Diagnostic Microdosing Approach to Investigate Platinum Sensitivity in Non-Small Cell Lung Cancer

Abstract

The platinum-based drugs cisplatin, carboplatin and oxaliplatin are often used for chemotherapy, but drug resistance is common. The prediction of resistance to these drugs via genomics is a challenging problem since hundreds of genes are involved. A possible alternative is to use mass spectrometry to determine the propensity for cells to form drug-DNA adducts—the pharmacodynamic drug-target complex for this class of drugs. The feasibility of predictive diagnostic microdosing was assessed in non-small cell lung cancer (NSCLC) cell culture and a pilot clinical trial. Accelerator mass spectrometry (AMS) was used to quantify [¹⁴C]carboplatin-DNA monoadduct levels in the cell lines induced by microdoses and therapeutic doses of carboplatin, followed by correlation with carboplatin IC₅₀ values for each cell line. The adduct levels in cell culture experiments were linearly proportional to dose (R²=0.95, p<0.0001) and correlated with IC₅₀ across all cell lines for microdose and therapeutically relevant carboplatin concentrations (p=0.02 and p=0.01, respectively). A pilot microdosing clinical trial was conducted to define protocols and gather preliminary data. Plasma pharmacokinetics (PK), and [¹⁴C]carboplatin-DNA adducts in white blood cells and tumor tissues from six NSCLC patients were quantified via AMS. The blood plasma half-life of [¹⁴C]carboplatin administered as a microdose was consistent with the known PK of therapeutic dosing. The optimal [¹⁴C]carboplatin formulation for the microdose was 10⁷ dpm/kg of body weight and 1% of the therapeutic dose for the total mass of carboplatin. No microdose-associated toxicity was observed in the patients. Additional accruals are required to significantly correlate adduct levels with response. This article is protected by copyright. All rights reserved.

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Prognostic relevance of miR-124-3p and its target TP53INP1 in pediatric ependymoma

Abstract

Ependymoma is a malignant pediatric brain tumor, often incurable under the current treatment regimen. We aimed to evaluate the expression of microRNAs (miRs) in pediatric ependymoma tumors in an attempt to identify prognostic molecular markers which would lead to potential therapeutic targets. Following miR-array expression analysis, we focused on 9 miRs that correlated with relapse which were further validated by quantitative real time PCR (qRT-PCR) in a cohort of 67 patients. Western blotting and immunohistochemistry were used to measure target protein expression in 20 and 34 tumor samples, respectively. High expression of miR-124-3p significantly correlated with the lower progression-free survival (PFS) of 16% compared to 67% in those expressing low levels (p=0.002). Interestingly, in the group of patients with local disease (n=56) expression levels of this miR distinguished 2 subgroups with a significantly different outcome (p=0.001). miR-124-3p was identified as an independent prognostic factor of relapse in the multivariate analysis performed in the whole cohort and in the group with localized disease. In the localized group, a patient expressing high levels of miR-124-3p had a 4.1-fold increased risk for relapse (p=0.005). We demonstrated the direct binding of miR-124-3p to its target TP53INP1. Negative TP53INP1 protein levels correlated with a poor outcome (p=0.034). We propose miR-124-3p and TP53INP1 as new biomarkers for prognostic stratification that may be possible therapeutic targets for ependymoma. This article is protected by copyright. All rights reserved.

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TCRP1 promotes NIH/3T3 cell transformation by over-activating PDK1 and AKT1

TCRP1 promotes NIH/3T3 cell transformation by over-activating PDK1 and AKT1

Oncogenesis 6, e323 (April 2017). doi:10.1038/oncsis.2017.18

Authors: C Wang, H Liu, Q Qiu, Z Zhang, Y Gu & Z He

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CRB3 downregulation confers breast cancer stem cell traits through TAZ/β-catenin

CRB3 downregulation confers breast cancer stem cell traits through TAZ/β-catenin

Oncogenesis 6, e322 (April 2017). doi:10.1038/oncsis.2017.24

Authors: P Li, Y Wang, X Mao, Y Jiang, J Liu, J Li, J Wang, R Wang, J She, J Zhang, J Yang, Y Liu & P Liu

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TCRP1 promotes NIH/3T3 cell transformation by over-activating PDK1 and AKT1

TCRP1 promotes NIH/3T3 cell transformation by over-activating PDK1 and AKT1

Oncogenesis 6, e323 (April 2017). doi:10.1038/oncsis.2017.18

Authors: C Wang, H Liu, Q Qiu, Z Zhang, Y Gu & Z He

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CRB3 downregulation confers breast cancer stem cell traits through TAZ/β-catenin

CRB3 downregulation confers breast cancer stem cell traits through TAZ/β-catenin

Oncogenesis 6, e322 (April 2017). doi:10.1038/oncsis.2017.24

Authors: P Li, Y Wang, X Mao, Y Jiang, J Liu, J Li, J Wang, R Wang, J She, J Zhang, J Yang, Y Liu & P Liu

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The safety and efficacy of percutaneous intraductal radiofrequency ablation in unresectable malignant biliary obstruction: A single-institution experience

Abstract

Background

Patients with unresectable malignant biliary obstruction have limited life expectancy because of limited stent patency and tumor progression. The aim of our study was to retrospectively evaluate the safety and efficacy of combining intraductal RFA with biliary metal stent placement for patients with malignant biliary obstruction.

Methods

Patients who received percutaneous intraductal RFA and biliary stent placement for malignant biliary obstruction between 2013 and 2015 were identified. Outcomes were stent patency, technique and clinical success rate, overall survival (OS) and complication rates. Kaplan-Meier and Cox regression analyses were used to examine the association of various factors with stent patency and OS. Complications and laboratory abnormalities were recorded.

Results

Fifty patients were treated with percutaneous RFA and stent placement. The rates of technical success and clinical success were 98% and 92%, respectively. The median stent patency was 7.0 (95% confidence interval [CI]: 5.3, 8.7) months and OS was 5.0 (95% CI: 4.0, 6.0) months. On univariable analysis, previously cholangitis was an independent poor prognosis factor for recurrent biliary obstruction. OS was improved in patients who received more than one intervention compared to those who received only one intervention (log-rank P = 0.007), and in those treated without versus those treated with sequential chemotherapy (log-rank P = 0.017). On multivariable analysis, the occurrence of more than one intervention (P = 0.019) had independent prognostic significance for OS.

Conclusion

Percutaneous RFA and stent placement is a technically safe and feasible therapeutic option for the palliative treatment of malignant biliary obstruction. The long-term efficacy and safety of the procedure is promising, but further study is required via randomized and prospective trials.

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The safety and efficacy of percutaneous intraductal radiofrequency ablation in unresectable malignant biliary obstruction: A single-institution experience

Abstract

Background

Patients with unresectable malignant biliary obstruction have limited life expectancy because of limited stent patency and tumor progression. The aim of our study was to retrospectively evaluate the safety and efficacy of combining intraductal RFA with biliary metal stent placement for patients with malignant biliary obstruction.

Methods

Patients who received percutaneous intraductal RFA and biliary stent placement for malignant biliary obstruction between 2013 and 2015 were identified. Outcomes were stent patency, technique and clinical success rate, overall survival (OS) and complication rates. Kaplan-Meier and Cox regression analyses were used to examine the association of various factors with stent patency and OS. Complications and laboratory abnormalities were recorded.

Results

Fifty patients were treated with percutaneous RFA and stent placement. The rates of technical success and clinical success were 98% and 92%, respectively. The median stent patency was 7.0 (95% confidence interval [CI]: 5.3, 8.7) months and OS was 5.0 (95% CI: 4.0, 6.0) months. On univariable analysis, previously cholangitis was an independent poor prognosis factor for recurrent biliary obstruction. OS was improved in patients who received more than one intervention compared to those who received only one intervention (log-rank P = 0.007), and in those treated without versus those treated with sequential chemotherapy (log-rank P = 0.017). On multivariable analysis, the occurrence of more than one intervention (P = 0.019) had independent prognostic significance for OS.

Conclusion

Percutaneous RFA and stent placement is a technically safe and feasible therapeutic option for the palliative treatment of malignant biliary obstruction. The long-term efficacy and safety of the procedure is promising, but further study is required via randomized and prospective trials.

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Modified frailty index predicts postoperative outcomes in older gastrointestinal cancer patients

Background and Objectives

Frailty disproportionately impacts older patients with gastrointestinal cancer, rendering them at increased risk for poor outcomes. A frailty index may aid in preoperative risk stratification. We hypothesized that high modified frailty index (mFI) scores are associated with adverse outcomes after tumor resection in older, gastrointestinal cancer patients.

Methods

Patients (60-90 years old) who underwent gastrointestinal tumor resection were identified in the 2005-2012 NSQIP Participant Use File. mFI was defined by 11 previously described, preoperative variables. Frailty was defined by an mFI score >0.27. The postoperative course was evaluated using univariate and multivariate analysis.

Results

41 455 patients (mean age 72.4 years, 47.4% female) were identified. The most prevalent form of cancer was colorectal (69.3%, n = 28 708) and 2.8% of patients were frail (n = 1,164). Frail patients were significantly more likely to have increased length of stay (11.7 vs 9.0 days), major complications (29.1% vs 17.9%), and 30-day mortality (5.6% vs 2.5%), (all P < 0.001). Multivariate analysis identified mFI as an independent predictor of major complications (OR 1.52, 95%CI 1.39-1.65, P < 0.001) and 30-day mortality (OR 1.48, 95%CI 1.24-1.75, P < 0.001).

Conclusions

mFI was associated with the incidence of postoperative complications and mortality in older surgical patients with gastrointestinal cancer.

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Impact of a risk-based follow-up in patients affected by gastrointestinal stromal tumour

Publication date: June 2017
Source:European Journal of Cancer, Volume 78
Author(s): Lorenzo D'Ambrosio, Erica Palesandro, Paola Boccone, Francesco Tolomeo, Sara Miano, Danilo Galizia, Antonio Manca, Gabriele Chiara, Ilaria Bertotto, Filippo Russo, Delia Campanella, Tiziana Venesio, Dario Sangiolo, Ymera Pignochino, Dimitrios Siatis, Michele De Simone, Alessandro Ferrero, Alberto Pisacane, Angelo Paolo Dei Tos, Sandra Aliberti, Massimo Aglietta, Giovanni Grignani
BackgroundFollow-up aims to precociously identify recurrences, metastases or treatment-related adverse events so as to undertake the appropriate therapy. Guidelines admit lack of knowledge on optimal surveillance schedule, but suggest follow-up based on experts' opinion and risk stratification. To identify the impact, if any, of regular follow-up, we interrogated our prospectively collected database whether early detection of recurrences affected both clinical management and, likely, the outcome.Patients and methodsWe required information to be available on primary surgery and ≥3°years of follow-up for non-recurring patients. We analysed recurrence characteristics (asymptomatic versus symptomatic, low- versus high tumour burden) and computed tomography (CT) scan counts to detect one recurrence. Kaplan–Meier method estimated recurrence-free survival (RFS), post-recurrence progression-free survival (PR-PFS), and disease-specific overall survival (OS). Comparisons used Hazard ratios (HR) with 95% confidence intervals (CIs). Multivariate analyses employed the Cox proportional hazards model. All tests were two-sided.ResultsBetween 01/2001 and 12/2012 we found 233 study-eligible patients. Estimated 5- and 10-year RFS were 61.8% and 50.4%, respectively. After a 68-month median follow-up, we observed 94 (40.3%) recurrences [73/94 (77.7%) asymptomatic versus 21/94 (22.3%) symptomatic and 45/94 (47.9%) low- versus 49/94 (52.1%) high tumour burden]. Multivariate analysis revealed that symptomatic and high tumour burden recurrences were highly predictive of both worse PR-PFS (HR:3.19, P < 0.001; HR:2.80, P = 0.003, respectively) and OS (HR:3.65, P < 0.001; HR:2.38, P = 0.026, respectively). Finally, 29 second (primary) cancers were detected during follow-up.ConclusionsRegular follow-up detects recurrences at an earlier stage and may be associated with a better PR-PFS and OS for these patients. In the absence of randomised trials, these evidences support follow-up effort and cost.



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Therapeutic efficacy of α-radioimmunotherapy with different activity levels of the 213 Bi-labeled monoclonal antibody MX35 in an ovarian cancer model

Abstract

Background

The aim of this study was to compare the therapeutic efficacy of two different activity levels of the ²¹³Bi-labeled monoclonal antibody MX35 in an ovarian cancer model. Sixty female BALB/c (nu/nu) mice were inoculated intraperitoneally with human ovarian cancer cells (OVCAR-3). Two weeks later, 40 mice were injected intraperitoneal (i.p.) with 1 ml of ²¹³Bi-MX35, 3 MBq/mL (n = 20), or 9 MBq/mL (n = 20). An additional 20 mice received unlabeled MX35. Incidence of tumors and ascites was investigated 8 weeks after therapy. Body weight and white blood cell counts were monitored after treatment for possible signs of toxicity.

Results

The tumor-free fraction of the animals treated with 3 MBq/mL of ²¹³Bi-MX35 was 0.55, whereas that of animals treated with 9 MBq/mL of ²¹³Bi-MX35 was 0.78. The control group treated with unlabeled MX35 had a tumor-free fraction of 0.15. No significant reduction in white blood cell counts or weight loss was observed.

Conclusions

Tumor growth after i.p. treatment with ²¹³Bi-MX35 was significantly reduced compared to treatment with unlabeled MX35. Treatment with 9 MBq/mL of ²¹³Bi-MX35 resulted in higher tumor-free fraction compared with 3 MBq/mL of ²¹³Bi-MX35, but this difference was not statistically significant. No signs of toxicity were observed in the treated animals.

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Effective dose estimation for oncological and neurological PET/CT procedures

Abstract

Background

The aim of this study was to retrospectively evaluate the patient effective dose (ED) for different PET/CT procedures performed with a variety of PET radiopharmaceutical compounds.

PET/CT studies of 210 patients were reviewed including Torso (n = 123), Whole body (WB) (n = 36), Head and Neck Tumor (HNT) (n = 10), and Brain (n = 41) protocols with ¹⁸FDG (n = 170), ¹¹C-CHOL (n = 10), ¹⁸FDOPA (n = 10), ¹¹C-MET (n = 10), and ¹⁸F-florbetapir (n = 10). ED was calculated using conversion factors applied to the radiotracer activity and to the CT dose-length product.

Results

Total ED (mean ± SD) for Torso-¹¹C-CHOL, Torso-¹⁸FDG, WB-¹⁸FDG, and HNT-¹⁸FDG protocols were 13.5 ± 2.2, 16.5 ± 4.5, 20.0 ± 5.6, and 15.4 ± 2.8 mSv, respectively, where CT represented 77, 62, 69, and 63% of the protocol ED, respectively. For ¹⁸FDG, ¹⁸FDOPA, ¹¹C-MET, and ¹⁸F-florbetapir brain PET/CT studies, ED values (mean ± SD) were 6.4 ± 0.6, 4.6 ± 0.4, 5.2 ± 0.5, and 9.1 ± 0.4 mSv, respectively, and the corresponding CT contributions were 11, 14, 23, and 26%, respectively. In ¹⁸FDG PET/CT, variations in scan length and arm position produced significant differences in CT ED (p < 0.01). For dual-time-point imaging, the CT ED (mean ± SD) for the delayed scan was 3.8 ± 1.5 mSv.

Conclusions

The mean ED for body and brain PET/CT protocols with different radiopharmaceuticals ranged between 4.6 and 20.0 mSv. The major contributor to total ED for body protocols is CT, whereas for brain studies, it is the PET radiopharmaceutical.

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Therapeutic efficacy of α-radioimmunotherapy with different activity levels of the 213 Bi-labeled monoclonal antibody MX35 in an ovarian cancer model

Abstract

Background

The aim of this study was to compare the therapeutic efficacy of two different activity levels of the ²¹³Bi-labeled monoclonal antibody MX35 in an ovarian cancer model. Sixty female BALB/c (nu/nu) mice were inoculated intraperitoneally with human ovarian cancer cells (OVCAR-3). Two weeks later, 40 mice were injected intraperitoneal (i.p.) with 1 ml of ²¹³Bi-MX35, 3 MBq/mL (n = 20), or 9 MBq/mL (n = 20). An additional 20 mice received unlabeled MX35. Incidence of tumors and ascites was investigated 8 weeks after therapy. Body weight and white blood cell counts were monitored after treatment for possible signs of toxicity.

Results

The tumor-free fraction of the animals treated with 3 MBq/mL of ²¹³Bi-MX35 was 0.55, whereas that of animals treated with 9 MBq/mL of ²¹³Bi-MX35 was 0.78. The control group treated with unlabeled MX35 had a tumor-free fraction of 0.15. No significant reduction in white blood cell counts or weight loss was observed.

Conclusions

Tumor growth after i.p. treatment with ²¹³Bi-MX35 was significantly reduced compared to treatment with unlabeled MX35. Treatment with 9 MBq/mL of ²¹³Bi-MX35 resulted in higher tumor-free fraction compared with 3 MBq/mL of ²¹³Bi-MX35, but this difference was not statistically significant. No signs of toxicity were observed in the treated animals.

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Effective dose estimation for oncological and neurological PET/CT procedures

Abstract

Background

The aim of this study was to retrospectively evaluate the patient effective dose (ED) for different PET/CT procedures performed with a variety of PET radiopharmaceutical compounds.

PET/CT studies of 210 patients were reviewed including Torso (n = 123), Whole body (WB) (n = 36), Head and Neck Tumor (HNT) (n = 10), and Brain (n = 41) protocols with ¹⁸FDG (n = 170), ¹¹C-CHOL (n = 10), ¹⁸FDOPA (n = 10), ¹¹C-MET (n = 10), and ¹⁸F-florbetapir (n = 10). ED was calculated using conversion factors applied to the radiotracer activity and to the CT dose-length product.

Results

Total ED (mean ± SD) for Torso-¹¹C-CHOL, Torso-¹⁸FDG, WB-¹⁸FDG, and HNT-¹⁸FDG protocols were 13.5 ± 2.2, 16.5 ± 4.5, 20.0 ± 5.6, and 15.4 ± 2.8 mSv, respectively, where CT represented 77, 62, 69, and 63% of the protocol ED, respectively. For ¹⁸FDG, ¹⁸FDOPA, ¹¹C-MET, and ¹⁸F-florbetapir brain PET/CT studies, ED values (mean ± SD) were 6.4 ± 0.6, 4.6 ± 0.4, 5.2 ± 0.5, and 9.1 ± 0.4 mSv, respectively, and the corresponding CT contributions were 11, 14, 23, and 26%, respectively. In ¹⁸FDG PET/CT, variations in scan length and arm position produced significant differences in CT ED (p < 0.01). For dual-time-point imaging, the CT ED (mean ± SD) for the delayed scan was 3.8 ± 1.5 mSv.

Conclusions

The mean ED for body and brain PET/CT protocols with different radiopharmaceuticals ranged between 4.6 and 20.0 mSv. The major contributor to total ED for body protocols is CT, whereas for brain studies, it is the PET radiopharmaceutical.

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Serous adenocarcinoma of retroperitoneum: a case report

Abstract

Primary retroperitoneal serous adenocarcinoma (PRSA) is an extremely rare malignancy, with only seven cases having been previously reported. We report a case of PRSA in a 42-year-old woman treated with surgical resection and adjuvant chemotherapy. The histopathological findings of PRSA resemble those of ovarian serous carcinoma, which indicates that a combination of complete surgical resection with adjuvant chemotherapy may be the best treatment option for PRSA.

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Serous adenocarcinoma of retroperitoneum: a case report

Abstract

Primary retroperitoneal serous adenocarcinoma (PRSA) is an extremely rare malignancy, with only seven cases having been previously reported. We report a case of PRSA in a 42-year-old woman treated with surgical resection and adjuvant chemotherapy. The histopathological findings of PRSA resemble those of ovarian serous carcinoma, which indicates that a combination of complete surgical resection with adjuvant chemotherapy may be the best treatment option for PRSA.

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CKS1BP7, a Pseudogene of CKS1B, is Co-Amplified with IGF1R in Breast Cancers

Abstract

Pseudogenes have been reported to exhibit functional roles. Amplification or overexpression of CDC28 protein kinase regulatory subunit 1B (CKS1B) was found in various human cancers. But it was known little about CKS1B pseudogene 7 (CKS1BP7), a pseudogene sharing considerable sequence identity with CKS1B. The aim of this study was to evaluate copy number alterations (CNAs) of CKS1BP7 and address its potential roles in breast cancer. We detected copy numbers of CKS1BP7 and insulin-like growth factor 1 receptor (IGF1R) using quantitative multi-gene fluorescence in situ hybridization (QM-FISH) technique, compared their status in both invasive carcinoma and ductal carcinoma in situ (DCIS) components within the same tumors, and investigated the associations of CNAs with tumor features and patients outcomes. Amplification of CKS1BP7 (dot-like pattern) was found in 28.8% of all cases, while amplified IGF1R (cluster pattern) was identified in 24.2% of all patients. The two events often co-existed (p = 0.01). Within the same tumors, identical CNAs of CKS1BP7 and IGF1R were found in DCIS and invasive carcinoma. Moreover, amplification of both genes was more frequent in aneuploidy tumors and the tumors with high ki67, but wasn't associated with patients' outcome. In summary, CKS1BP7 amplification is a frequent event in breast cancer and often co-occurs with amplified IGF1R, which provides evidence supporting the interactions between CKS1BP7 and IGF1R during mammary carcinogenesis. Our findings suggest that CKS1BP7 as well as IGF1R may serve as potential biomarkers for early detection and predict prognosis in breast cancer.

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Histiocytic sarcoma: New insights into FNA cytomorphology and molecular characteristics

BACKGROUND

Histiocytic sarcoma (HS) is a rare malignant neoplasm showing morphologic and immunophenotypic features of histiocytes. Molecular characteristics of HS and fine-needle aspiration (FNA) criteria for its diagnosis have not been established.

METHODS

A case series of HS in 8 FNA samples from 6 patients was reviewed along with histopathologic and clinical data. Immunohistochemistry was performed on cell blocks (3 cases), core biopsies (5 cases), and surgical specimens (4 cases). Targeted-exome next-generation sequencing (NGS) was performed on surgical resection specimens in 4 cases.

RESULTS

Four patients had a known history of hematolymphoid malignancy. Cytomorphologic features included variably cellular smears composed of large epithelioid cells with reniform nuclei and abundant vacuolated cytoplasm, in an inflammatory background, with occasional cytophagocytosis and lymphoglandular bodies. Marked pleomorphism, multinucleated monster cells, and binucleated histiocytoid cells with partially overlapping, eccentrically placed nuclei resembling Pac-Man were common. Most cases expressed histiocytic markers CD68 (6 of 7 cases), CD163 (5 of 5 cases), and PU.1 (3 of 4 cases). In 3 cases, NGS analysis revealed alterations in lysine methyltransferase 2D (KMT2D)/mixed-lineage leukemia 2 (MLL2), a gene involved in chromatin regulation and previously implicated in the pathogenesis of follicular lymphoma.

CONCLUSIONS

Although diagnosing HS with FNA alone is extremely challenging, the presence of pleomorphic and epithelioid large cells with binucleation and/or multinucleation in an inflammatory background should prompt the diagnosis of HS with judicious use of confirmatory histiocytic lineage markers. The detection of recurrent KMT2D/MLL2 alterations implicates epigenetic regulation in the pathogenesis of HS and supports the notion of transdifferentiation from a genetically similar but phenotypically distinct tumor of a different lineage. Cancer Cytopathol 2017. © 2017 American Cancer Society.

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“…That which we call a Rose…”: A critical analysis of rapid on-site evaluation

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Histiocytic sarcoma: New insights into FNA cytomorphology and molecular characteristics

BACKGROUND

Histiocytic sarcoma (HS) is a rare malignant neoplasm showing morphologic and immunophenotypic features of histiocytes. Molecular characteristics of HS and fine-needle aspiration (FNA) criteria for its diagnosis have not been established.

METHODS

A case series of HS in 8 FNA samples from 6 patients was reviewed along with histopathologic and clinical data. Immunohistochemistry was performed on cell blocks (3 cases), core biopsies (5 cases), and surgical specimens (4 cases). Targeted-exome next-generation sequencing (NGS) was performed on surgical resection specimens in 4 cases.

RESULTS

Four patients had a known history of hematolymphoid malignancy. Cytomorphologic features included variably cellular smears composed of large epithelioid cells with reniform nuclei and abundant vacuolated cytoplasm, in an inflammatory background, with occasional cytophagocytosis and lymphoglandular bodies. Marked pleomorphism, multinucleated monster cells, and binucleated histiocytoid cells with partially overlapping, eccentrically placed nuclei resembling Pac-Man were common. Most cases expressed histiocytic markers CD68 (6 of 7 cases), CD163 (5 of 5 cases), and PU.1 (3 of 4 cases). In 3 cases, NGS analysis revealed alterations in lysine methyltransferase 2D (KMT2D)/mixed-lineage leukemia 2 (MLL2), a gene involved in chromatin regulation and previously implicated in the pathogenesis of follicular lymphoma.

CONCLUSIONS

Although diagnosing HS with FNA alone is extremely challenging, the presence of pleomorphic and epithelioid large cells with binucleation and/or multinucleation in an inflammatory background should prompt the diagnosis of HS with judicious use of confirmatory histiocytic lineage markers. The detection of recurrent KMT2D/MLL2 alterations implicates epigenetic regulation in the pathogenesis of HS and supports the notion of transdifferentiation from a genetically similar but phenotypically distinct tumor of a different lineage. Cancer Cytopathol 2017. © 2017 American Cancer Society.

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“…That which we call a Rose…”: A critical analysis of rapid on-site evaluation

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Desmoid-Type Fibromatosis: Who, When, and How to Treat

Opinion statement

Desmoid-type fibromatosis is a sarcoma subtype that gathers some singular characteristics, making it a difficult challenge to face in clinical practice. Despite its excellent survival prognosis, these tumors may be unpredictable, ranging from an asymptomatic indolent course to persistent, local, and extended recurrences that significantly impair quality of life. Although surgery was initially considered the first elective treatment, collected published data during the past few years are now pointing to the "wait and see" approach as a reasonable initial strategy because many patients can live a long life with the disease without having symptoms. When symptoms appear or there is a risk of functional impairment, a wide spectrum of therapies (local and systemic) can be useful in improving symptoms and controlling the disease. Because of the low incidence of desmoid-type fibromatosis, there is scarce scientific evidence supporting any specific treatment. Nonetheless, if volumetric responses are needed, chemotherapy may be a reasonable early option. However, if long-term control of disease is desirable, hormonal therapy, NSAIDs, and TKIs are the likely treatments of choice. Recent new findings in the biologic development of these tumors, such as the role of Wnt/β-catenin dependent pathway, have shown that the prognostic information provided by specific CTNNB1 gene mutations and other genetic profiles can lead to better methods of selecting patients as candidates for other approaches. Based on recent research, the Notch pathway inhibition in DF is one of the most promising potential targets to explore. As an orphan disease, it is mandatory that as many patients as possible be included in clinical trials.

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The Changing Landscape of Genetic Testing for Inherited Breast Cancer Predisposition

Opinion statement

The advent of multiple-gene germline panel testing has led to significant advances in hereditary breast and ovarian cancer risk assessment. These include guideline-specific cancer risk management recommendations for patients and their families, such as screening with breast magnetic resonance imaging and risk-reducing surgeries, which have the potential to reduce substantially the morbidity and mortality associated with a hereditary cancer predisposition. However, controversy remains about the clinical validity and actionability of genetic testing in a broader patient population. We discuss events leading to the wider availability of commercialized multiple-gene germline panel testing, the recent data that support using this powerful tool to improve cancer risk assessment and reduction strategies, and remaining challenges to clinical optimization of this new genetic technology.

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Adjuvant Endocrine Therapy in Breast Cancer : Evolving Paradigms in Premenopausal Women

Opinion statement

In the last few years, new adjuvant endocrine treatment options have become available in young women with early breast cancer, such as the addition of ovarian function suppression to tamoxifen or aromatase inhibitors. Treatment duration has been also adapted in the latest guidelines based on the individual risk of recurrence. The oncologist is therefore challenged to precisely assess the risk of recurrence according to currently available predictive and prognostic factors in order to offer the most appropriate therapeutic option to the individual patient, considering also potential side effects, quality of life, pregnancy planning and patients' preferences. The adjuvant treatment planning should always be discussed and agreed in a multidisciplinary context. Tamoxifen remains the standard of care in low-risk patients or in case of intolerance to combined treatment with pharmacological ovarian function suppression or aromatase inhibitors. Combination treatment is indicated in intermediate high-risk disease. The patient should always be considered an active partner in the treatment decision process, to improve treatment motivation and adherence. Finally, the therapeutic choice should take into account drug availability and pharmacoeconomic issues, which unfortunately may prevent, in many low-income countries, the provision of such effective treatments.

http://ift.tt/2q6OpRb

Desmoid-Type Fibromatosis: Who, When, and How to Treat

Opinion statement

Desmoid-type fibromatosis is a sarcoma subtype that gathers some singular characteristics, making it a difficult challenge to face in clinical practice. Despite its excellent survival prognosis, these tumors may be unpredictable, ranging from an asymptomatic indolent course to persistent, local, and extended recurrences that significantly impair quality of life. Although surgery was initially considered the first elective treatment, collected published data during the past few years are now pointing to the "wait and see" approach as a reasonable initial strategy because many patients can live a long life with the disease without having symptoms. When symptoms appear or there is a risk of functional impairment, a wide spectrum of therapies (local and systemic) can be useful in improving symptoms and controlling the disease. Because of the low incidence of desmoid-type fibromatosis, there is scarce scientific evidence supporting any specific treatment. Nonetheless, if volumetric responses are needed, chemotherapy may be a reasonable early option. However, if long-term control of disease is desirable, hormonal therapy, NSAIDs, and TKIs are the likely treatments of choice. Recent new findings in the biologic development of these tumors, such as the role of Wnt/β-catenin dependent pathway, have shown that the prognostic information provided by specific CTNNB1 gene mutations and other genetic profiles can lead to better methods of selecting patients as candidates for other approaches. Based on recent research, the Notch pathway inhibition in DF is one of the most promising potential targets to explore. As an orphan disease, it is mandatory that as many patients as possible be included in clinical trials.

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The Changing Landscape of Genetic Testing for Inherited Breast Cancer Predisposition

Opinion statement

The advent of multiple-gene germline panel testing has led to significant advances in hereditary breast and ovarian cancer risk assessment. These include guideline-specific cancer risk management recommendations for patients and their families, such as screening with breast magnetic resonance imaging and risk-reducing surgeries, which have the potential to reduce substantially the morbidity and mortality associated with a hereditary cancer predisposition. However, controversy remains about the clinical validity and actionability of genetic testing in a broader patient population. We discuss events leading to the wider availability of commercialized multiple-gene germline panel testing, the recent data that support using this powerful tool to improve cancer risk assessment and reduction strategies, and remaining challenges to clinical optimization of this new genetic technology.

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Adjuvant Endocrine Therapy in Breast Cancer : Evolving Paradigms in Premenopausal Women

Opinion statement

In the last few years, new adjuvant endocrine treatment options have become available in young women with early breast cancer, such as the addition of ovarian function suppression to tamoxifen or aromatase inhibitors. Treatment duration has been also adapted in the latest guidelines based on the individual risk of recurrence. The oncologist is therefore challenged to precisely assess the risk of recurrence according to currently available predictive and prognostic factors in order to offer the most appropriate therapeutic option to the individual patient, considering also potential side effects, quality of life, pregnancy planning and patients' preferences. The adjuvant treatment planning should always be discussed and agreed in a multidisciplinary context. Tamoxifen remains the standard of care in low-risk patients or in case of intolerance to combined treatment with pharmacological ovarian function suppression or aromatase inhibitors. Combination treatment is indicated in intermediate high-risk disease. The patient should always be considered an active partner in the treatment decision process, to improve treatment motivation and adherence. Finally, the therapeutic choice should take into account drug availability and pharmacoeconomic issues, which unfortunately may prevent, in many low-income countries, the provision of such effective treatments.

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Serum G-CSF May Be a More Valuable Biomarker than Image Evaluation in G-CSF-Producing Urothelial Carcinoma: A Case Report

Granulocyte colony-stimulating factor (G-CSF)-producing urothelial carcinomas (UCs) are rare and have a poor prognosis. According to the literature, treatment for G-CSF-producing UCs is very difficult. We experienced 2 cases of UC presenting with leukocytosis. In these cases, serum G-CSF levels were higher than the reference value with leukocytosis at diagnosis, and the resected specimens were positive for anti-G-CSF immunostaining. One case had a good prognosis and the other case died after 9 months from diagnosis. A change in serum G-CSF levels was reportedly an effective tumor marker in several reports. In the present cases, evaluation of serum G-CSF levels was found to be more sensitive than computerized tomography. The treatment and outcomes of UC-producing G-CSFs and the efficacy of serum G-CSF as a tumor marker are discussed based on our cases and a review of the literature.
Case Rep Oncol 2017;10:377–382

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Sarcoidosis-Lymphoma Syndrome Associated with Folliculotropic Peripheral T Cell Lymphoma Not Otherwise Specified

Sarcoidosis is occasionally accompanied by hematologic malignancies, including cutaneous T-cell lymphoma, called sarcoidosis-lymphoma syndrome. Although the mechanism underlying the induction of lymphomas is still unknown, understanding the immunological background of sarcoidosis could help explain the possible mechanisms of the induction of lymphomas. In this report, we describe a case of sarcoidosis-lymphoma syndrome associated with folliculotropic peripheral T cell lymphoma not otherwise specified, which caused dense infiltration of CD30+ CD163+ tumor-associated macrophages (TAMs) only in the lesional skin. Our present case might suggest the significance of TAMs in developing sarcoid-lymphoma syndrome.
Case Rep Oncol 2017;10:372–376

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Successful Treatment of Sudden Hepatitis Induced by Long-Term Nivolumab Administration

Immune checkpoint inhibitors have drastically changed in the treatment of many kinds of malignancies, especially malignant melanoma. The focus of the recent experiments has not only been on their efficacy but also immune-related adverse events (irAEs). We report a case of fulminant hepatitis due to nivolumab. In this case, the patient had undergone long-term nivolumab therapy. He did not complain of any symptoms but his liver enzyme levels were extremely elevated (grade 4). We promptly decided to start oral corticosteroids in the patient. His liver function rapidly improved. The dose of corticosteroids was gradually reduced. Our case demonstrates that sudden onset fulminant hepatitis can occur despite the safe use of long-term nivolumab therapy. The irAE can improve rapidly with proper corticosteroid treatment. This report will be useful for the physicians who always use immune checkpoint inhibitors.
Case Rep Oncol 2017;10:368–371

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Nivolumab Therapy for Synchronous ALK-Positive Lung Cancer and Gastric Cancer

Nivolumab is an immune checkpoint inhibitor with demonstrated efficacy against several malignant tumors. Alterations in driver oncogenes such as EGFR and ALK are a poor prognostic factor in nivolumab therapy for non-small cell lung cancer (NSCLC), whereas a smoking history is a well-known, favorable prognostic factor. However, an efficacy of nivolumab therapy for multiple primary malignant tumors (MPMTs) has not been reported, and its efficacy for driver oncogene-positive NSCLC in smokers is unclear. Herein, we report the case of a patient with a history of heavy smoking who developed synchronous ALK-positive NSCLC and gastric cancer that responded to nivolumab therapy. A 76-year-old man who was a heavy smoker presented to our hospital with symptoms of hoarseness and dysphagia. He was ultimately diagnosed with ALK-positive advanced NSCLC. An ALK inhibitor (alectinib) was administered, and the lung cancer lesions showed improvement. The alectinib therapy was continued for 5 months. Thereafter, the lesions in the left lower lobe of the lung showed regrowth. During the same period, the patient experienced epigastric pain. Gastrointestinal endoscopy examination revealed gastric cancer. He was administered nivolumab to treat both the lung cancer and the gastric cancer. Two months later, both the lung lesions and the gastric lesions had diminished in size. Nivolumab therapy might be an effective therapy for synchronous MPMTs and NSCLC in heavy smokers, even if the lung cancer possesses driver oncogene mutations.
Case Rep Oncol 2017;10:361–367

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The Key Genes of Chronic Pancreatitis which Bridge Chronic Pancreatitis and Pancreatic Cancer Can be Therapeutic Targets

Abstract

An important question in systems biology is what role the underlying molecular mechanisms play in disease progression. The relationship between chronic pancreatitis and pancreatic cancer needs further exploration in a system view. We constructed the disease network based on gene expression data and protein-protein interaction. We proposed an approach to discover the underlying core network and molecular factors in the progression of pancreatic diseases, which contain stages of chronic pancreatitis and pancreatic cancer. The chronic pancreatitis and pancreatic cancer core network and key factors were revealed and then verified by gene set enrichment analysis of pathways and diseases. The key factors provide the microenvironment for tumor initiation and the change of gene expression level of key factors bridge chronic pancreatitis and pancreatic cancer. Some new candidate genes need further verification by experiments. Transcriptome profiling-based network analysis reveals the importance of chronic pancreatitis genes and pathways in pancreatic cancer development on a system level by computational method and they can be therapeutic targets.

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Nothing left to chance? The impact of locus of control on physical and mental quality of life in terminal cancer patients

Abstract

Purpose

The purpose of this study is to evaluate if locus of control (LOC) predicts various quality of life (QOL) and mental well-being measures among terminally ill cancer patients at the time of palliative care consult.

Methods

Multi-site analysis of patients with advanced cancer being seen as new patients in a Palliative and Supportive Care outpatient clinic. Patients completed the following surveys: locus of control (LOC) scale, Functional Assessment of Chronic Illness Therapy-General (FACT-G), Functional Assessment of Chronic Illness Therapy–Spiritual (FACIT-Sp), Hospital Anxiety Depression Scale (HADS), and Herth Hope Index (HHI).

Regression models were created to examine the effect of LOC upon QOL, symptoms, and other measures of mental well-being. These models adjusted for the effect of age, gender, race, partnership status, education, and months since diagnosis as potential confounders.

Results

This study enrolled 100 patients. After adjusting for site, race, and partnership status, higher levels of LOC chance predicted decreased QOL (FACT-G) (p < 0.01). Higher levels of LOC chance also correlated with increased depression and anxiety (p ≤ 0.01) and decreased meaning/peace and faith (p ≤ 0.01). Additionally, higher levels of LOC chance predicted decreased hope (HHI) (p ≤ 0.001).

Conclusions

Terminally ill cancer patients with a high LOC chance may be at risk for decreased physical and mental well-being at the end of life. Efforts should be made to identify these patients and design interventions to increase their feeling of control over the situation in order to improve physical and mental well-being at the end of life.

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Impact of recommended weight-based dosing of granulocyte-colony stimulating factors in acute leukemia and stem cell transplant patients

Abstract

Purpose

Febrile neutropenia (FN) is a major risk factor for infection-related morbidity and mortality. The National Comprehensive Cancer Network recommends the prophylactic use of granulocyte-colony stimulating factors (G-CSF), dosed at 5 mcg/kg and rounded to the nearest vial size. A previous medication use evaluation conducted within a multi-hospital healthcare system demonstrated that only 67% of patients were started on appropriate weight-based dosing. The purpose of this study was to evaluate the effect of appropriate weight-based G-CSF dosing in patients on clinical outcomes.

Methods

A retrospective chart review of patients with acute leukemia or stem cell transplant recipients who received G-CSF from May 2009 to September 2015 was conducted. Patient admissions were reviewed in regards to neutropenia length, incidence of FN, length of stay, and final disposition (alive or deceased). Admissions were divided into one of three weight-based dosing groups of under 5 mcg/kg, recommended 5 mcg/kg within a 10% range, and over 5 mcg/kg which were named under, recommended, and over, respectively.

Results

Ninety-four admissions were included. Average age of this patient population was 58 years old, and the majority of patients were male (53%) and Caucasian (55%). Majority of patients had been diagnosed with acute myeloid leukemia (91%). Data showed average duration of neutropenia was around 10 days regardless if the patient received under 5 mcg/kg, the recommended 5 mcg/kg or over 5 mcg/kg G-CSF (10.1 ± 6.7 days, 8.9 ± 9.2 days, 10.1 ± 9.1 days, respectively). Length of stay was similar for patients regardless of initial G-CSF dose (29.6 ± 16.0 days, 29.1 ± 18.4 days, and 24.5 ± 17.0, respectively). However, the incidence of FN was significantly greater for those who received under 5 mcg/kg of G-CSF (87% for under, 68% for recommended, and 54% for over).

Conclusions

In this retrospective analysis, variations from the recommended 5 mcg/kg G-CSF dose did not significantly impact length of neutropenia, length of stay, nor mortality. However, patients who received under the 5 mcg/kg of G-CSF dose may be at a greater risk of FN.

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Preemptive treatment with Xonrid®, a medical device to reduce radiation induced dermatitis in head and neck cancer patients receiving curative treatment: a pilot study

Abstract

Purpose

The purpose of this study was to investigate efficacy, safety and tolerability of Xonrid®, a new medical device, in preventing radiation dermatitis associated with head and neck cancer (HNC) radiotherapy (RT).

Methods

In this monocentric, prospective pilot study, adult consecutive HNC patients who were planned to receive curative RT with or without chemotherapy were enrolled. Patients were instructed to apply Xonrid® on the irradiated area during treatment continuing until 2 weeks after the completion of RT or the development of severe skin toxicity. Toxicity was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 scale. The patient reported outcome measures included the Skindex-16 questionnaire and patient satisfaction. Skin reflectance spectra were analyzed to objectively evaluate dermatitis.

Results

In total, 41 subjects were enrolled (30 males, median age 60 years). No skin adverse events were recorded either in the skin area where the product was applied or in the nearby skin over the entire period of administration. At the end of RT, nine patients (22%) presented G1, 31 (76%) G2, and one patient (2%) G3 skin toxicity (after 5 weeks). Seven and 20 patients reached skin maximum toxicity at the fourth week and after the seventh week, respectively. An increasing trend of median spectrophotometry scores along with skin toxicity grades was observed. A correlation between Skindex-16 scores and skin toxicity grade during treatment was found.

Conclusions

Our study results suggest that Xonrid® is well tolerated, safe, and effective in minimizing and delaying high-grade radiation dermatitis in HNC patients.

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Development of depression in survivors of childhood and adolescent cancer: a multi-level life course conceptual framework

Abstract

As therapeutic and supportive care interventions become increasingly effective, growing numbers of childhood and adolescent cancer survivors face a myriad of physical and psychological sequelae secondary to their disease and treatment. Mental health issues, in particular, present a significant problem in this unique patient population, with depression affecting a sizable number of childhood and adolescent cancer survivors. Multiple key determinants impact a survivor's risk of developing depression, with variables traversing across biologic, individual, family, community, and global levels, as well as spanning throughout the life course of human development from the preconception and prenatal periods to adulthood. A multi-level life course conceptual model offers a valuable framework to identify and organize the diverse variables that modulate the risk of developing depression in survivors of childhood and adolescent cancer. This review describes the first multi-level life course perspective applied to development of depression in childhood and adolescent cancer survivors. This conceptual framework may be used to guide the investigation of mental health interventions for SCACs to ensure that key determinants of depression occurrence are adequately addressed across various levels and throughout the life trajectory.

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Disease burden and pain in obese cancer patients with chemotherapy-induced peripheral neuropathy

Abstract

Purpose

Chemotherapy-induced peripheral neuropathy (CIPN) and obesity are prevalent in cancer survivors and decrease quality of life; however, the impact of the co-occurrence of these conditions has garnered little attention. This study investigated differences between obese and non-obese cancer survivors with CIPN and predictors of symptom burden and pain.

Methods

Patients with CIPN were administered the MD Anderson Symptom Inventory and a modified version of pain descriptors from the McGill Pain Inventory. Independent t tests assessed group differences between obese and non-obese survivors, and linear regression analyses explored predictors of patient outcomes.

Results

Results indicated a significant difference in symptom severity scores for obese (M = 32.89, SD = 25.53) versus non-obese (M = 19.35, SD = 16.08) patients (t(37.86) = −2.49, p = .02). Significant differences were also found for a total number of pain descriptors endorsed by obese (M = 4.21, SD = 3.45) versus non-obese (M = 2.42, SD = 2.69) participants (t(74) = −2.53, p = .01). Obesity was a significant predictor of symptom severity and total pain descriptors endorsed. Other significant predictors included age and months since treatment.

Conclusions

Cancer survivors with CIPN and co-occurring obesity may be more at risk for decreased quality of life through increased symptom severity and pain compared to non-obese survivors. This paper identified risk factors, including obesity, age, and months since treatment, that can be clinically identified for monitoring distress in CIPN patients. Future research should focus on the longitudinal relationship between obesity and CIPN, and robust interventions to address the multifaceted issues faced by cancer survivors.

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Perceptions of family members of palliative medicine and hospice patients who experienced music therapy

Abstract

Purpose

Evidence shows that music therapy aids in symptom management and improves quality of life for palliative medicine and hospice patients. The majority of previous studies have addressed patient needs, while only a few addressed the needs of family members. The primary purpose of this study was to understand family members' perceptions of music therapy experienced by a relative in palliative medicine or hospice. Patient self-reported scales and music therapist assessment of change were also investigated.

Methods

Patients scored their symptoms (pain, anxiety, depression, shortness of breath, and mood) before and after music therapy sessions. One family member present during the session assessed perceived effect on the patient's pain, anxiety, depression, shortness of breath, stress level, restlessness, comfort level, mood, and quality of life. The effect on family member's stress level, quality of life, and mood and helpfulness of the music therapy session for the patient and self were studied. Recommendations about future patient participation in music therapy and qualitative comments were also solicited.

Results

Fifty family member/patient dyads participated in the study. Family member perceptions were positive, with 82% of responders indicating improvement for self and patient in stress, mood, and quality of life; 80% rating the session as extremely helpful; and 100% of 49 recommending further music therapy sessions for the patient. Patients reported statistically significant improvement in pain, depression, distress, and mood scores.

Conclusions

Family members of patients in palliative medicine and hospice settings reported an immediate positive impact of music therapy on the patient and on themselves. More research needs to be conducted to better understand the benefits of music therapy for family members.

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Comparison of integrative medicine centers in the USA and Germany: a mixed method study

Abstract

Purpose

Integrative medicine (IM) has received increasing attention since the 1990s, but few studies have explored the key factors of the IM model in health care. This study aimed to describe the IM model in leading centers operating in the USA and Germany.

Methods

A 28-item structured survey and semi-structured interviews were conducted in six centers providing integrative medicine in the USA and Germany, and were analyzed using a convergent mixed-method approach.

Results

The elements in common across all six centers were the following: (1) involvement of general physicians (GP) in delivering complementary and alternative medicine (CAM) services; (2) requirement for GP or medical referral or recommendation to CAM services; (3) involvement of an integrative physician (IP) as a "gatekeeper"; (4) focus on research, education, and clinical practice; and (5) ongoing academic activities. The key elements differentiating the two countries were the following: (1) level of requirements for GP referral to CAM services; (2) differences in IM service delivery, including treatment modalities used; (3) accessibility of CAM services to patients; (4) interaction between team members and patients; (5) perception of CAM/IM; and (6) perception of patient-centered care. Themes underpinning these elements are the following: cultural aspects in conceptualizing IM health care; communication within IM programs; and resource availability for delivering IM services, which impacts patient engagement and team collaboration in the IM framework.

Conclusions

Delivering IM health care requires a model of care that encourages interaction between all stakeholders. Developing a comprehensive conceptual framework to support IM practice is required to facilitate efficient and safe patient care.

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A predictive model of inflammatory markers and patient-reported symptoms for cachexia in newly diagnosed pancreatic cancer patients

Abstract

Background

Cachexia is a frequent manifestation of pancreatic cancer, can limit a patient's ability to take chemotherapy, and is associated with shortened survival. We developed a model to predict the early onset of cachexia in advanced pancreatic cancer patients.

Methods

Patients with newly diagnosed, untreated metastatic or locally advanced pancreatic cancer were included. Serum cytokines were drawn prior to therapy. Patient symptoms were recorded using the M.D. Anderson Symptom Inventory (MDASI). Our primary endpoint was either 10% weight loss or death within 60 days of the start of therapy.

Results

Twenty-seven of 89 patients met the primary endpoint (either having lost 10% of body weight or having died within 60 days of the start of treatment). In a univariate analysis, smoking, history symptoms of pain and difficulty swallowing, high levels of MK, CXCL-16, IL-6, TNF-a, and low IL-1b all correlated with this endpoint. We used recursive partition to fit a regression tree model, selecting four of 26 variables (CXCL-16, IL-1b, pain, swallowing difficulty) as important in predicting cachexia. From these, a model of two cytokines (CXCL-16 > 5.135 ng/ml and IL-1b < 0.08 ng/ml) demonstrated a better sensitivity and specificity for this outcome (0.70 and 0.86, respectively) than any individual cytokine or tumor marker.

Conclusions

Cachexia is frequent in pancreatic cancer; one in three patients met our endpoint of 10% weight loss or death within 60 days. Inflammatory cytokines are better than conventional tumor markers at predicting this outcome. Recursive partitioning analysis suggests that a model of CXCL-16 and IL-1B may offer a better ability than individual cytokines to predict this outcome.

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Association between bone scan index and activities of daily living in patients with advanced non-small cell lung cancer

Abstract

Purpose

The aim of this retrospective cross-sectional study was to investigate the association between the bone scan index (BSI) and activities of daily living (ADL) in patients with advanced non-small cell lung cancer (NSCLC).

Methods

Among patients with advanced NSCLC, subjects who underwent bone scintigraphy were recruited from this study. Clinical information about patients, including the Barthel Index of ADL, was extracted from their medical charts. Variables including the age, sex, BSI, presence/absence skeletal-related events (SREs), diagnostic state (initial vs. relapse), and history of use of certain medications (e.g. opiates) were evaluated as factors possibly associated with the Barthel Index. In Addition, associations between these factors, including the Barthel Index, with the overall survival were also assessed.

Results

A total of 111 patients with bone metastases were selected. The BSI and Barthel Index of the patients were 1.59 ± 2.25 and 69.7 ± 19.6, respectively. Multivariable analysis identified age (≥70 years), a high BSI (≥1.0), and presence of SREs were as factors statistically significantly associated with lower values of the Barthel Index (<75). On the other hand, Cox proportional hazards analysis identified low values of the Barthel Index (<75), use of opiates, and male sex as significant factors associated with a shorter overall survival; the BSI was not associated with the overall survival in the patients with advanced NSCLC in this study.

Conclusion

The results suggest that a high BSI (≥1.0) is an independent predictor of poor ADL in patients with NSCLC, while showing no correlation with the overall survival.

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Longitudinal patterns of bone-targeted agent use among patients with solid tumors and bone metastases in the United States

Abstract

Purpose

This study examined real-world long-term use of guideline-recommended bone targeted agents (BTA) among patients with metastatic solid tumors.

Methods

Adults with a solid tumor diagnosis followed by a bone metastasis diagnosis in 2012–2014 were identified from electronic medical records in the Oncology Services Comprehensive Electronic Records (OSCER) database. Patients initiated zoledronic acid (ZA) or denosumab on or after the bone metastasis diagnosis and were followed through last clinic visit by 30 June 2015. We describe time to BTA initiation, compliance (≥12 administrations in a year), switching, and non-persistence (switch or ≥90 day gap in therapy), by agent and follow-up period.

Results

The majority of the 14,881 study patients (50% female, 65% age ≥65 years) had breast (33%), prostate (26%), or lung (26%) tumors. Half of all patients initiated on each agent, with denosumab initiations exceeding ZA initiations in 2014. Most (91% denosumab, 93% ZA) initiations occurred within 3 months of bone metastasis diagnosis. At 1, 2, and 3 years post-initiation, denosumab patients were less likely to switch agents (4, 3, and 1% versus 14, 12, and 11%) and more likely to be compliant (50, 37, and 31% versus 41, 26, and 6%). Median time to non-persistence was 25.9 months for denosumab and 17.2 months for ZA, p < 0.0001.

Conclusions

This is the first study reporting long-term treatment patterns for the two primary BTAs used in the USA. The greater compliance and longer persistence observed among denosumab patients may improve treatment effectiveness achieved in the real-world setting.

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Characteristics of advanced cancer patients who were readmitted to an acute palliative/supportive care unit

Abstract

Objectives

The aim of this study was to assess the characteristics of patients readmitted to an acute supportive/palliative care unit (ASPCU), the reasons for readmission, and the outcome after receiving specialistic assessment and treatment.

Methods

A consecutive sample of patients was assessed for a period of 10 months. Epidemiological characteristics, including age, gender, Karnofsky level, diagnosis, caregivers, education, disease awareness, kind of admission, and anticancer treatment in the previous 30 days, were recorded, as well as hospital stay, death, and discharge at home. The principal reasons for admission were recorded. Symptom intensity and opioid doses, expressed as oral morphine equivalents, were also measured.

Results

In the study period, 79 (25.2%) readmissions were recorded. Thirty-seven (46.8%) readmissions occurred within 30 days after discharge. Pain was more frequently reported as indication for admission at the first and the second readmission in comparison with the first admission. The burden of symptoms was significantly higher in patients with a readmission in comparison with patients at the first admission. Opioid doses, expressed as oral morphine equivalents, were significantly different between the first admission and readmissions. In both patients at the first admission or readmission, a significant decrease in symptom intensity has been reported at discharge.

Conclusion

About 25% of patients discharged from an ASCPU are expected to be readmitted for reemerging of clinical problems. Re-exacerbation of pain seems to be the most frequent reason. A further clinical reassessment and treatment were equally effective in controlling the symptom burden of these patients at any readmission.

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Effectiveness of antiemetic triplet therapy with aprepitant, palonosetron, and dexamethasone for gynecologic cancer patients receiving carboplatin and paclitaxel: a prospective single-arm study

Abstract

Purpose

There is no positive evidence for the efficacy of antiemetic triplet therapy with aprepitant (APR), palonosetron (PALO), and dexamethasone (DEX) for moderate emetogenic chemotherapy, especially for gynecologic malignancies. Thus, the present study evaluated the efficacy of this triplet therapy in patients receiving carboplatin and paclitaxel (CP) for gynecologic malignancy.

Methods

Seventy patients with gynecologic cancer receiving CP were enrolled into a prospective single-arm study with APR (125 mg on day 1, 80 mg on days 2–3), PALO (0.75 mg), and DEX (20 mg) before initiating chemotherapy. The primary endpoint was delayed complete response (CR) rate, i.e., no vomiting and no rescue, at 24–120 h after chemotherapy administration.

Results

Seventy patients were enrolled. The delayed CR rate was 97.1% (68/70). No serious adverse events were observed. Younger patient age (≤50 years) tended to be associated with a poor delayed CR rate.

Conclusions

This study demonstrated a notable efficacy of antiemetic triplet therapy with APR, PALO, and DEX in female patients receiving CP. Further evaluation with a larger phase III trial is warranted.

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Emesis and nausea related to single agent trabectedin in ovarian cancer patients: a sub-study of the MITO15 project

Abstract

The MITO 15 was a prospective, single-arm trial, evaluating trabectedin monotherapy in patients with recurrent ovarian cancer (OC) who were BRCA mutation-carriers or had a BRCAness phenotype. It is largely reported that trabectedin may induce nausea and vomiting but the real emetogenic potential of the drug, in the different schedules, has never been fully described; furthermore, OC patients are known to have an enhanced risk of developing nausea and vomiting due to female gender, abdominal spreading of the disease, and major surgery experienced by most of them. We thought to carry on a sub-study in the MITO 15 context focused on chemotherapy-induced nausea and vomiting (CINV) associated with trabectedin single agent. For all patients enrolled in the trial, we evaluated the antiemetic regimen at the first cycle, acute and delayed CINV, any rescue therapy, any change in the prophylactic antiemetic regimen, and the potential relationship between dexamethasone dosage and incidence of CINV. Overall, our findings were consistent with literature and confirmed that trabectedin can be classified as moderately emetogenic. We observed slightly higher rates of both nausea and vomiting compared to previous experiences with trabectedin monotherapy, probably due to intrinsic features of our population: all females and suffering from ovarian cancer. It seems that in preventing acute CINV, the combination of three drugs was more effective than the doublet; however, the difference did not reach statistical significance; further studies are required to verify such hypothesis. Given the extreme heterogeneity of the antiemetic regimens used, it appears that a standard antiemetic protocol does not exist and more specific guidelines for clinicians are needed.

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Enhancing accrual to chemotherapy trials for patients with early stage triple-negative breast cancer: a survey of physicians and patients

Abstract

Purpose

The optimal chemotherapy regimen for patients with early stage triple-negative breast cancer (TNBC) remains unknown. The purpose of the study is to survey physicians and breast cancer patients about preferred chemotherapy regimens for early stage TNBC and clinical trial strategies.

Methods

A standardised online questionnaire was developed and circulated to medical oncologists known to treat breast cancer. A separate questionnaire was given to patients who had received chemotherapy for breast cancer.

Results

The questionnaire was completed by 41/84 medical oncologists (48.8% response rate) and 74 patients. The most commonly used neoadjuvant and adjuvant chemotherapy regimens for TNBC were dose-dense doxorubicin and cyclophosphamide (AC)–paclitaxel (P), dose-dense AC followed by weekly P and fluorouracil, epirubicin, cyclophosphamide–docetaxel (FEC-D). The majority of medical oncologists (80%) would be willing to enrol patients in trials evaluating the most effective chemotherapy regimen for TNBC. Oncologists favoured a three arm trial design comparing currently available standard of care treatments (36%) and trials of novel or non-standard of care agents 22% (9/41). Sixty percent (41/74) of patients indicated that they would be willing to be enrolled in trials evaluating various adjuvant regimens for TNBC. Both oncologists and patients were interested in novel consent approaches such as using the integrated consent model.

Conclusion

Optimisation of chemotherapy for TNBC is an important and unmet clinical need. It is apparent that various chemotherapy regimens are used for patients with early stage TNBC. The majority of medical oncologists and patients are interested in entering trials to optimise chemotherapy choices.

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Patient’s experiences of being discharged home from hospital following a diagnosis of malignant spinal cord compression

Abstract

Purpose

The purpose of this study is to explore experiences in the days and weeks following discharge home following diagnosis and treatment for metastatic spinal cord compression (MSCC).

Methods

Eleven participants took part in audio-recorded semi-structured interviews about their experiences at 1 and 3–4 weeks post-discharge home following a diagnosis of MSCC. Transcripts were analysed using a framework approach.

Results

Time emerged as an overarching theme within the framework of four time points: past, present, near future and distant future. Themes included getting home, challenges at home, community support, getting back to normal, in limbo, long-term goals and coping strategies.

Conclusion

Getting to a level of coping at home after discharge following MSCC can take time. Services need to address this so that patients can live well within the limitations they face.

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Effects of compensatory cognitive training intervention for breast cancer patients undergoing chemotherapy: a pilot study

Abstract

Purpose

Numerous breast cancer patients experience cognitive changes during and after chemotherapy. Chemotherapy-related cognitive impairment can significantly affect quality of life. This pilot study attempted to determine the effects of a compensatory cognitive training on the objective and subjective cognitive functioning of breast cancer patients receiving adjuvant chemotherapy.

Methods

Fifty-four patients were assigned to either a compensatory cognitive training or waitlist condition. They were assessed at baseline (T1), the completion of the 12-week intervention (T2), and 6 months after intervention completion (T3). Outcomes were assessed using the standardized neuropsychological tests and the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), version 3. Raw data were converted to T-scores based on baseline scores, and a repeated-measures ANCOVA, adjusting for age, intelligence, depression, and treatment, was used for analysis. The effect sizes for differences in means were calculated.

Results

The intervention group improved significantly over time compared to the waitlist group on objective cognitive function. Among ten individual neuropsychological measures, immediate memory, delayed memory, verbal fluency in category, and verbal fluency in letter showed significant group × time interaction. In subjective cognitive function, scores of the waitlist group significantly decrease over time on perceived cognitive impairments, in contrast to those of the intervention group.

Conclusion

The 12-week compensatory cognitive training significantly improved the objective and subjective cognitive functioning of breast cancer patients. Because this was a pilot study, further research using a larger sample and longer follow-up durations is necessary.

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Urine drug screen findings among ambulatory oncology patients in a supportive care clinic

Abstract

Purpose

Professional organizations provide no guidelines regarding assessment and management of opioid abuse risk in cancer. Universal precautions (UP) developed for non-cancer pain, include assessments for aberrant behavior, screening questionnaires, and urine drug screens (UDS). The role of UDS for identifying opioid abuse risk in cancer is uncertain. Our aim is to characterize inappropriate UDS, and identify a potential role for UDS in therapeutic decision-making.

Methods

An observational retrospective chart review of 232 consecutive supportive care clinic patients were seen during the study. Twenty-eight of the two hundred thirty-two did not meet inclusion criteria. One hundred fifty of the two hundred four had active cancer, while 54 had no evidence of active disease. Clinicians ordered UDS based on their clinical judgment of patients' substance misuse risk. Edmonton symptom assessment scores, history of substance abuse, alcohol use, tobacco use, aberrant behavior, and morphine equivalent daily dose (MEDD) were obtained.

Results

Pain scores and MEDD were higher (p = 0.021; p < 0.001) in the UDS group vs non-UDS. Forty percent of the patients (n = 82/204) had at least one UDS and 70% (60/82) had an inappropriate result. Thirty-nine percent (32) were inappropriately negative, showing no prescribed opioids. Forty-nine of the eighty-two were positive for non-prescribed opioids, benzodiazepine, or illicit substance. Eleven of the forty-nine had only cannabis metabolites in their urine. There were no significant differences between appropriate and inappropriate UDS groups regarding pain scores, MEDD or referral to psychology, psychiatry, or substance abuse specialists.

Conclusions

UDS on the 82 oncology patients at high risk for substance misuse were frequently positive (46%) for non-prescribed opioids, benzodiazepines or potent illicit drugs such as heroin or cocaine, and 39% had inappropriately negative UDS, raising concerns for diversion.

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A prospective study of changes in anxiety, depression, and problems in living during chemotherapy treatments: effects of age and gender

Abstract

Purpose

Monitoring distress assessment in cancer patients during the treatment phase is a component of good quality care practice. Yet, there is a dearth of prospective studies examining distress. In an attempt to begin filling this gap and inform clinical practice, we conducted a prospective, longitudinal study examining changes in distress (anxiety, depression, and problems in living) by age and gender and the roles of age and gender in predicting distress.

Methods

Newly diagnosed Brazilian cancer patients (N = 548) were assessed at three time points during chemotherapy. Age and gender were identified on the first day of chemotherapy (T1); anxiety, depression, and problems in living were self-reported at T1, the planned midway point (T2), and the last day of chemotherapy (T3).

Results

At T1, 37 and 17% of patients reported clinically significant levels of anxiety and depression, respectively. At T3, the prevalence was reduced to 4.6% for anxiety and 5.1% for depression (p < .001). Patients 40–55 years, across all time points, reported greater anxiety and practical problems than patients >70 years (p < .03). Female patients reported greater emotional, physical, and family problems than their male counterparts (p < .04).

Conclusions

For most patients, elevated levels of distress noted in the beginning of treatment subsided by the time of treatment completion. However, middle-aged and female patients continued to report heightened distress. Evidence-based psychosocial intervention offered to at risk patients during early phases of the treatment may provide distress relief and improve outcomes over the illness trajectory while preventing psychosocial and physical morbidity due to untreated chronic distress.

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Assessment of the integration between oncology and palliative care in advanced stage cancer patients

Abstract

Purpose

Chemotherapy is indicated for patients with metastatic malignancy in order to improve quality of life and in some cases to increase survival. However, the greatest difficulty regarding the choice of treatment is to evaluate the clinical benefit and intrinsic toxicity of each procedure. The best strategy is the integration between oncology and palliative care, which is still mostly insufficient. The main objective of this study was to assess time to palliative care referral for cancer patients with advanced local or metastatic disease and to investigate the impact of covariates on this relationship.

Methods

A retrospective, cross-sectional, observational pilot study was conducted on 286 patients divided into two groups, one consisting of metastatic patients and the other of non-metastatic patients at diagnosis. Karnofsky Performance Scale (KPS), setting, and survival time were evaluated.

Results

One hundred eighteen patients (41.25%) were metastatic and 168 (58.74%) had locally advanced malignant disease. The median time of metastatic patient referral to the group of palliative care (GPC) was 5.3 months, with 39.8% referred earlier and 60.2% referred late (≥3 months). 60.2% of metastatic patients were referred to the GPC with a KPS <70% and 56% of non-metastatic patients were referred earlier and 44% after 3 months. There was improved survival only in metastatic patients referred to the GPC with a KPS ≥70% (p = 0.02).

Conclusions

Many oncology patients were referred late to the GPC. A higher KPS was a risk factor for late referral because only severe patients were referred earlier. Metastatic patients referred with a KPS ≥70% had a longer survival.

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Effective chemotherapy of heterogeneous and drug-resistant early colon cancers by intermittent dose schedules: a computer simulation study

Abstract

Purpose

The effectiveness of cancer chemotherapy is limited by intra-tumor heterogeneity, the emergence of spontaneous and induced drug-resistant mutant subclones, and the maximum dose to which normal tissues can be exposed without adverse side effects. The goal of this project was to determine if intermittent schedules of the maximum dose that allows colon crypt maintenance could overcome these limitations, specifically by eliminating mixtures of drug-resistant mutants from heterogeneous early colon adenomas while maintaining colon crypt function.

Methods

A computer model of cell dynamics in human colon crypts was calibrated with measurements of human biopsy specimens. The model allowed simulation of continuous and intermittent dose schedules of a cytotoxic chemotherapeutic drug, as well as the drug's effect on the elimination of mutant cells and the maintenance of crypt function.

Results

Colon crypts can tolerate a tenfold greater intermittent dose than constant dose. This allows elimination of a mixture of relatively drug-sensitive and drug-resistant mutant subclones from heterogeneous colon crypts. Mutants can be eliminated whether they arise spontaneously or are induced by the cytotoxic drug.

Conclusions

An intermittent dose, at the maximum that allows colon crypt maintenance, can be effective in eliminating a heterogeneous mixture of mutant subclones before they fill the crypt and form an adenoma.

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Co-administration of proton pump inhibitors ameliorates nephrotoxicity in patients receiving chemotherapy with cisplatin and fluorouracil: a retrospective cohort study

Abstract

Purpose

The nephrotoxicity of cisplatin (CDDP) is its dose-limiting side effect, and is caused by renal accumulation of CDDP mainly via organic cation transporter 2 (OCT2). Because proton pump inhibitors (PPIs) are known to inhibit OCT2 activity, PPI might ameliorate CDDP-induced nephrotoxicity. In the present study, we retrospectively investigated the effect of co-administration of PPI on CDDP-induced nephrotoxicity.

Methods

We analyzed the impact of PPI on the development of nephrotoxicity in 133 patients who received CDDP and fluorouracil (5-FU) therapy for the treatment of esophageal cancer or head and neck cancer. Nephrotoxicity that developed within 14 days following CDDP administration was evaluated in accordance with Common Terminology Criteria for Adverse Events ver. 4.0 for acute kidney injury.

Results

The rate of nephrotoxicity in patients with PPI (12%, n = 33) was significantly lower than that in patients without PPI (30%, n = 100). Severe nephrotoxicity greater than Grade 2 was not observed in patients with PPI, whereas the rate of hematological toxicity was comparable between patients with and without PPI. Kaplan–Meier analysis showed that the time to nephrotoxicity following CDDP administration was significantly prolonged in patients with PPI. Multivariate analysis revealed that co-administration of PPI with CDDP and 5-FU was an independent factor significantly contributing to the amelioration of nephrotoxicity (odds ratio 0.239, p = 0.033).

Conclusions

These findings indicate that co-administration of clinical doses of PPI could ameliorate nephrotoxicity without exacerbation of hematological toxicity in patients receiving CDDP and 5-FU therapy.

http://ift.tt/2q70ndp