Inhibition of STAT3 enhances the radiosensitizing effect of temozolomide in glioblastoma cells in vitro and in vivo

Abstract

Even with aggressive treatment involving radiation therapy plus temozolomide (TMZ), the prognosis for glioblastoma remains poor. We investigated the potential for targeting signal transducer and activator of transcription-3 (STAT3) to improve the therapeutic outcome in glioblastoma. We evaluated the preclinical potential of a STAT3 inhibitor, Cpd188, combined with temozolomide and radiation using in vitro assays with two established glioblastoma cell lines (U251 and U87) and two patient-derived glioblastoma cell lines (GBL12 and GBL28) as well as in vivo studies with nude mice bearing intracranial U251 xenografts. Cpd188 potentiated the radiosensitizing effect of TMZ in U251 cells, which have high p-STAT3 expression levels. The enhanced radiosensitizing effects of TMZ were associated with impaired DNA damage repair, apoptosis and reversion of the epithelial-mesenchymal transition (EMT). Cpd188 delayed in vivo tumor growth alone and in combination with radiation and TMZ. We also confirmed the radiosensitizing effect of Cpd188 in GBL28 cells, which were originated from a patient with a high level of STAT3 expression and unmethylated MGMT. Targeting STAT3 using Cpd188 could be a viable therapeutic approach for improving the outcome of current standard therapy in glioblastoma patients with high p-STAT3 expression.

from Cancer via ola Kala on Inoreader http://ift.tt/2aNI1bp
via IFTTT

A comparison of dosimetric parameters in PET-based active bone marrow volume and total bone volume in prediction of hematologic toxicity in cervical cancer patients treated with chemoradiation

Abstract

Objective

The purpose of this study is to evaluate whether dose to PET-defined active regions of the bone marrow is a better predictor of hematologic toxicity than dose to the total bone as a surrogate of the bone marrow.

Methods

Twenty-one patients with stage IB-IVB cervical cancer who had baseline PET imaging and underwent definitive cisplatin-based chemoradiation from 2010 to 2015 were reviewed. Total bone marrow (TBM) volume was defined as the bone from L4 to the coccyx, the pelvic bones, and proximal femoral heads. Active bone marrow (ABM) was defined by PET as the volume of the bone within the TBM greater than or equal to the mean total body standard uptake value (SUV). Dosimetric parameters evaluated were mean dose, V10, V20, and V40, which were compared by a t test. Hematologic toxicity was graded using Common Terminology Criteria for Adverse Events (CTCAEv4). Receiver operating characteristic (ROC) analysis was used to assess predictors of grade 3 or higher (grade 3+) hematologic toxicity.

Results

ABM volume (mean = 1227 mL, range 793–1671 mL) was significantly smaller than the TBM volume (mean = 1553 mL, range 1117–1920 mL) [p = 0.0001]. ROC analysis identified ABM volume (AUC = 0.800, p = 0.002) and V40 to the ABM (AUC = 0.800, p = 0.008) as the best predictors for grade 3+ hematologic toxicity. All ten patients with an ABM volume < 1201 mL had grade 3+ toxicity compared to 5/11 with an ABM volume > 1201 mL (Fisher's p = 0.012).

Conclusion

A lower volume of ABM at a baseline (<1201 mL) was highly predictive of grade 3+ hematologic toxicity.

from Cancer via ola Kala on Inoreader http://ift.tt/2bkc8Y3
via IFTTT

Changes in quality of life after radiation therapy for localized prostate cancer after dissemination of intensity modulated radiation therapy

Abstract

Objective

It is unclear whether the adoption of intensity-modulated radiation therapy (IMRT) for prostate cancer is associated with improved health-related quality of life (HRQOL). Therefore, we examined the HRQOL of elderly patients who had undergone external beam radiation therapy (EBRT) during two eras: 1998–2001, when 3D-CRT was the standard of care for EBRT, and 2006–2009, when IMRT was the dominant form of EBRT.

Methods

The Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey was used to obtain HRQOL measurements of Medicare beneficiaries who had received external beam radiotherapy for nonmetastatic prostate cancer. A total of 90 patients during the early era and 75 patients during the late era had eligible surveys both before and after diagnosis. Descriptive statistics and linear regression were used to compare change in HRQOL from baseline to follow-up as measured by physical and mental component scores between patients during the two different eras.

Results

During the first 2 years after treatment, mental component scores at follow-up among patients during the early era declined significantly but no such decline was observed among patients during the late era (beta = 5.18; p = 0.008 late vs. early era). No difference in change in physical component scores was found between the two eras.

Conclusions

HRQOL as measured by mental component scores were improved among prostate cancer patients in the era of IMRT compared to prior.

from Cancer via ola Kala on Inoreader http://ift.tt/2aCnGZl
via IFTTT

PDQ (Physician Data Query)

from Cancer via ola Kala on Inoreader http://ift.tt/2aCk0H9
via IFTTT

"P < 0.05" Might Not Mean What You Think: American Statistical Association Clarifies P Values

from Cancer via ola Kala on Inoreader http://ift.tt/2b5ylZi
via IFTTT

Engineered T Cells Improve Pancreatic Cancer Outcomes in Mice

from Cancer via ola Kala on Inoreader http://ift.tt/2b5xXtT
via IFTTT

Editorial Board

from Cancer via ola Kala on Inoreader http://ift.tt/2aCiWTz
via IFTTT

Tackling Mesothelioma With Immunotherapies

from Cancer via ola Kala on Inoreader http://ift.tt/2aCiyEI
via IFTTT

Mammaprint Reveals Who Can Skip Chemotherapy for Breast Cancer

from Cancer via ola Kala on Inoreader http://ift.tt/2b5yegu
via IFTTT

Cover

from Cancer via ola Kala on Inoreader http://ift.tt/2aCiVzi
via IFTTT

Physical Activity Associated With Fewer Cancers

from Cancer via ola Kala on Inoreader http://ift.tt/2b5xOq6
via IFTTT

Subscription

from Cancer via ola Kala on Inoreader http://ift.tt/2b5y8Fi
via IFTTT

Mesothelioma Death Rate by State, (1999-2010)

from Cancer via ola Kala on Inoreader http://ift.tt/2aCkBbG
via IFTTT

Table of Contents

from Cancer via ola Kala on Inoreader http://ift.tt/2b5xGXX
via IFTTT

Long-term Outcome of an Organ Preservation Program After Neoadjuvant Treatment for Rectal Cancer

Background: The aim of this study was to establish the oncological and functional results of organ preservation with a watch-and-wait approach (W&W) and selective transanal endoscopic microsurgery (TEM) in patients with a clinical complete or near-complete response (cCR) after neoadjuvant chemoradiation for rectal cancer.

Methods: Between 2004 and 2014, organ preservation was offered if response assessment with digital rectal examination, endoscopy, and MRI showed (near) cCR. Watch-and-wait was offered for cCR, and two options were offered for near cCR: TEM or reassessment after three months. Follow-up included endoscopy and MRIs every three months during the first year, and every six months thereafter. Long-term outcome was assessed with Kaplan-Meier curves. Functional outcome was assessed with colostomy-free survival and Vaizey incontinence score (0 = perfect continence, 24 = totally incontinent).

Results: One hundred patients were included, with median follow-up of 41.1 months. Sixty-one had cCR at initial response assessment. Thirty-nine had near cCR, of whom 24 developed cCR at the second assessment and 15 patients underwent TEM (9 ypT0, 1 ypT1, 5 ypT2). Fifteen patients developed a local regrowth (12 luminal, 3 nodal), all salvageable and within 25 months. Five patients developed metastases, and five patients died. Three-year overall survival was 96.6% (95% confidence interval [CI] = 89.9% to 98.9%), distant metastasis–free survival was 96.8% (95% CI = 90.4% to 99.0%), local regrowth–free survival was 84.6% (95% CI = 75.8% to 90.5%), and disease-free survival was 80.6% (95% CI = 70.9% to 87.4%). Colostomy-free survival was 94.8% (95% CI = 88.0% to 97.8%), with a good continence after watch-and-wait (Vaizey = 3.4, SD = 3.9) and moderate after TEM (Vaizey = 9.7, SD = 5.1).

Conclusions: Organ preservation appears oncologically safe for selected rectal cancer patients with a cCR or near cCR after neoadjuvant chemoradiation when applying strict selection criteria and frequent follow-up, including endoscopy and MRI. The low colostomy rate and the good long-term functional outcome warrant discussing this option with the patient as an alternative to major surgery.

from Cancer via ola Kala on Inoreader http://ift.tt/2aCiCEz
via IFTTT

Cancer incidence in holocaust male survivors – an israeli cohort study

Abstract

Previous studies, often using proxy exposure assessment and not controlling for individual risk factors, suggested higher cancer risk in Holocaust survivors. We have used individual-level data from a male cohort of Israeli civil servants recruited in 1963 to investigate cancer incidence in Holocaust survivors, controlling for potential confounders.

The analysis included 4,669 Europe-born subjects; 689 exposed=E (immigrated to Israel after 1939 and reported of being in Nazi camps during World War II); 2,307 potentially-exposed=PE (immigrated to Israel after 1939 and reported of not being in Nazi camps); and 1,673 non-exposed=NE (immigrated to Israel prior to 1939). Vital status and cancer incidence in the cohort were determined based on national registries. Socioeconomic level, health behaviors and cancer incidence were compared between the groups and Cox proportional hazards regression models adjusting for potential confounders assessed hazard risk ratios for cancer by exposure status. All-cause mortality was studied as a competing risk.

In total, 241, 682 and 522 cancer cases were diagnosed in the E, PE and NE, respectively. Compared to the NE, all-site cancer incidence was higher in the E (HR=1.13, 95%CI 0.97-1.32) but not in the PE. All-cause mortality competed with all-site invasive cancer incidence in the E group (HR=1.18, 95%CI 1.02-1.38). Colorectal and lung cancer seemed to be positively though non-significantly associated with the exposure while prostate cancer was not.

Male Holocaust survivors may be at a weakly increased risk for all-site, colorectal and lung cancer. The role of age at exposure and residual confounding should be further investigated. This article is protected by copyright. All rights reserved.

from Cancer via ola Kala on Inoreader http://ift.tt/2aCaTWY
via IFTTT

Cell autonomous or systemic EGFR blockade alters the immune-environment in squamous cell carcinomas

Abstract

Targeting mutations and amplifications in the EGFR has been successful precision therapy for cancers of the lung, oral cavity and gastrointestinal track. However, a systemic immune reaction manifested by dose-limiting inflammation in the skin and gut has been a consistent adverse effect. To address the possibility that intra-tumoral immune changes contribute to the anti-cancer activity of EGFR inhibition, squamous cancers were produced by syngeneic orthografts of either EGFR null or wildtype mouse primary keratinocytes transduced with an oncogenic H-ras retrovirus. Flow cytometric, RNA and Bioplex immunoassay analyses of the tumor immune milieu were performed. Cancers forming from keratinocytes genetically depleted of EGFR were smaller than wildtype cancers and had fewer infiltrating FoxP3 Treg cells, lower Foxp3 RNA and a lower percentage of CD4 PD1 positive cells indicating a tumor cell autonomous regulation of its microenvironment. Hosts bearing wildtype cancers treated with gefitinib for one week showed a trend for smaller tumors. In this short term pharmacological model, there was also a trend to reduced FoxP3 cells and FoxP3 RNA in the tumors of treated mice as well as a substantial increase in the ratio of IL-1A/IL-1RA transcripts. These results suggest that relatively brief systemic inhibition of EGFR signaling alters the immune environment of the targeted cancer. Together these data imply that an EGFR dependent Treg function supports the growth of squamous cancers and is a target for the therapeutic activity of EGFR inhibition. This article is protected by copyright. All rights reserved.

from Cancer via ola Kala on Inoreader http://ift.tt/2b5oAKq
via IFTTT

Molecular differences in the microsatellite stable phenotype between left-sided and right-sided colorectal cancer

Abstract

Differences in the pathogenesis of microsatellite stable (MSS) sporadic colorectal cancers (CRCs) between left-sided CRC (LC) and right-sided CRC (RC) have not been clarified. To identify pathogenesis-related genomic differences between MSS CRCs within the 2 locations, we performed a comprehensive molecular analysis using crypt isolation with samples from 92 sporadic CRCs. Microsatellite instability (MSI; high and low/negative) and DNA methylation status (low methylation epigenome [LME]; intermediate methylation epigenome [IME]; or high methylation epigenome [HME]) were determined using polymerase chain reaction (PCR) microsatellite analysis and PCR-bisulfite pyrosequencing, respectively. Additionally, mutations in the TP53, KRAS, BRAF, and PIK3CA genes were examined using PCR-bisulfite pyrosequencing (for KRAS and BRAF mutations) or PCR-single conformation polymorphism (for TP53 and PIK3CA mutations), followed by sequencing of aberrant bands. Finally, a genome-wide study using a copy number alteration (CNA)-targeted single nucleotide polymorphism array was performed. Ninety-two CRCs were classified into 71 MSS and 21 MSI phenotypes. We examined 71 CRCs with the MSS phenotype (LC 56; RC, 15). Mutations in KRAS were associated with RC with the MSS phenotype, whereas mutations in TP53 were more frequently found in LC with the MSS phenotype. There were significant differences in the frequencies of KRAS and TP53 mutations in the IME between LC and RC with the MSS phenotype. Although CNA gains were associated with LC with the MSS phenotype, CNA losses were not major alterations associated with the MSS phenotype. These findings suggested that the molecular pathogenesis of the MSS phenotype in LC was different from that in RC. This article is protected by copyright. All rights reserved.

from Cancer via ola Kala on Inoreader http://ift.tt/2aCaXWP
via IFTTT

A Cohort Study of Cervical Screening Using Partial HPV Typing and Cytology Triage

Abstract

HPV testing is more sensitive than cytology for cervical screening. However, to incorporate HPV tests into screening, risk-stratification ("triage") of HPV-positive women is needed to avoid excessive colposcopy and overtreatment. We prospectively evaluated combinations of partial HPV typing (Onclarity, BD) and cytology triage, and explored whether management could be simplified, based on grouping combinations yielding similar 3-year or 18-month CIN3+ risks. We typed ∼9,000 archived specimens, taken at enrollment (2007-2011) into the NCI-Kaiser Permanente Northern California (KPNC) HPV Persistence and Progression (PaP) cohort. Stratified sampling, with reweighting in the statistical analysis, permitted risk estimation of HPV/cytology combinations for the 700,000+-woman KPNC screening population. Based on 3-year CIN3+ risks, Onclarity results could be combined into 5 groups (HPV16, else HPV18/45, else HPV31/33/58/52, else HPV51/35/39/68/56/66/68, else HPV negative); cytology results fell into 3 risk groups ("high-grade", ASC-US/LSIL, NILM). For the resultant 15 HPV group-cytology combinations, 3-year CIN3+ risks ranged a thousand-fold from 60.6% to 0.06%. To guide management, we compared the risks to established "benchmark" risk/management thresholds in this same population (e.g., LSIL predicted 3-year CIN3+ risk of 5.8% in the screening population, providing the benchmark for colposcopic referral). By benchmarking to 3-year risk thresholds (supplemented by 18-month estimates), the widely varying risk strata could be condensed into 4 action bands (very high risk of CIN3+ mandating consideration of cone biopsy if colposcopy did not find precancer; moderate risk justifying colposcopy; low risk managed by intensified follow-up to permit HPV "clearance"; and very low risk permitting routine screening.) Overall, the results support primary HPV testing, with management of HPV-positive women using partial HPV typing and cytology. This article is protected by copyright. All rights reserved.

from Cancer via ola Kala on Inoreader http://ift.tt/2b5mV83
via IFTTT

Overexpression of long non-coding RNA NR_036575.1 contributes to the proliferation and migration of papillary thyroid cancer

Abstract

Current evidence suggests that the human genome produces a large number of non-coding RNAs, including microRNAs and long non-coding RNAs (lncRNAs). Generally, lncRNAs are defined as RNA transcripts longer than 200 nucleotides that are not transcribed into proteins. In recent years, lncRNAs have been reported to play oncogenic roles in tumourigenesis. However, minimal research has been performed on the expression and clinicopathological significance of lncRNAs in papillary thyroid cancer (PTC). In the present study, we investigated not only the expression and clinicopathological significance of a novel lncRNA, NR_036575.1, in PTC tissues and adjacent non-cancerous tissues but also its potential function in TPC1 cells. The expression levels of the lncRNA NR_036575.1 in 83 pairs of PTC tissues and adjacent non-cancerous tissues were detected via quantitative real-time polymerase chain reaction. The relationships between the expression levels and clinicopathological characteristics of the lncRNA NR_036575.1 were analysed. In addition, we established two receiver operating characteristic (ROC) curves to assess the diagnostic value of NR_036575.1 expression. Cell Counting Kit-8 and transwell assays were used to assess cell proliferation and migration, respectively. The expression levels of the lncRNA NR_036575.1 were significantly higher in PTC tissues than in adjacent non-cancerous tissues. High NR_036575.1 expression was associated with extrathyroidal extension (ETE) (P = 0.011) and tumour size (P = 0.006). The ROC curves indicated that NR_036575.1 could potentially serve as a biomarker for identifying PTC and related, non-cancerous diseases (sensitivity, 80.7 %; specificity, 88 %), as well as for differentiating between PTC with or without ETE (sensitivity, 57.8 %; specificity, 86.7 %). NR_036575.1 knock-down significantly inhibited the proliferation and migration of TPC1 cells. Our findings are the first to describe lncRNA NR_036575.1 overexpression in PTC. NR_036575.1 expression was associated with both ETE and tumour size. In addition, NR_036575.1 modulation could regulate TPC1 cell proliferation and migration. The results of our study suggest that NR_036575.1 could be applied as a potential biomarker and a novel therapeutic target for PTC patients.

from Cancer via ola Kala on Inoreader http://ift.tt/2bhF32Y
via IFTTT

Toxicity-Related Factors Associated With Use of Services Among Community Oncology Patients [FOCUS ON QUALITY]

Purpose:

Community oncology practices frequently manage chemotherapy-associated toxicities, which may disrupt treatment, impair quality of life, and induce unplanned service use. We sought to understand the patterns and correlates of unplanned health care service use among patients receiving first-cycle chemotherapy at five community-based ambulatory oncology practices.

Patients and Methods:

A survey study examined the dichotomous outcome of unplanned service use, defined as oncologist visits, emergency department visits, and hospitalizations, resulting from toxicity-related factors. Newly diagnosed patients with breast, lung, head and neck, or colorectal cancer or non-Hodgkin lymphoma were recruited during the first chemotherapy cycle. Before beginning the second cycle of chemotherapy, patients completed a questionnaire that measured unplanned service use and overall distress, plus severity of nausea, vomiting, diarrhea, constipation, mouth sores, intravenous catheter problems, pain, fever and chills, extremity edema, and dyspnea on a 5-point scale (1, did not experience; 5, disabling). Medical record reviews captured chemotherapy doses, comorbid conditions, and supportive care interventions. Mixed-effects logistic regression was used to identify factors associated with unplanned service use, with random effects specified for each clinic.

Results:

Among 106 patients (white, 98%; female, 74.5%; mean age ± standard deviation, 60 ± 11 years), frequently reported toxicities were pain, nausea, diarrhea, and constipation. Thirty-six patients (34%) reported unplanned service use: 29% reported oncologist visits, 14% reported emergency department visits, and 8% reported hospitalizations. Factors significantly associated with unplanned service use were high patient-reported distress and receipt of colony-stimulating factor.

Conclusion:

Service use resulting from toxicity-related factors occurs frequently in community oncology settings. Monitoring toxicity patterns and outcomes can inform proactive symptom management approaches to reduce toxicity burden between scheduled visits.

from Cancer via ola Kala on Inoreader http://ift.tt/2b5eERu
via IFTTT

Trial Design and Efficacy Thresholds for Granting Breakthrough Therapy Designation in Oncology [HEALTH POLICY]

Breakthrough therapy designation (BTD) is a new approach created by the US Congress and the US Food and Drug Administration (FDA) as part of the FDA Innovation and Safety Act of 2012 to expedite the drug development process for serious illness, including cancer. By law, to qualify for BTD, a new molecular entity must demonstrate substantial clinical improvement over existing therapies. Although the administrative requirements for granting BTD have been made available by the FDA, the actual trial designs, end points, and quantitative therapeutic thresholds involved in the granting process have not been made public. This literature review evaluates nine oncology new molecular entities granted BTD involved in 10 accelerated approvals and summarizes the key factors in clinical trial design leading to successful BTD applications. This information can be used by oncology research teams to set goals for BTD when developing clinical trial designs and thresholds in expedited drug development programs.

from Cancer via ola Kala on Inoreader http://ift.tt/2aC5Jdp
via IFTTT

Nonadherence to Oral Medications for Chronic Conditions in Breast Cancer Survivors [CARE DELIVERY]

Purpose:

Nonadherence to oral endocrine therapy is common among women with breast cancer (BC). Less is known about nonadherence to medications for other chronic conditions among survivors of BC.

Methods:

We used the MarketScan Database to identify women older than 18 years who had nonmetastatic BC diagnosed between January 1, 2009, and December 31, 2013. Prescriptions were identified for the following six non–cancer-related conditions: hypertension, thyroid disease, hyperlipidemia, gastroesophageal reflux disease, diabetes, and osteoporosis. The study period was defined as 1 year before BC diagnosis (index date) through 1.5 years after the index date, with a 6-month washout period after the index data to control for adherence during the preoperative period and during chemotherapy if necessary. Adherence was defined as a medication possession ratio ≥ 80%. Change in adherence was defined as a 20% decrease in the medication possession ratio from the time before diagnosis compared with after treatment. Factors associated with change in adherence were evaluated in multivariable logistic models.

Results:

Among 36,149 patients diagnosed with BC, the average adherence to these medications before BC was 91.4%. However, after BC treatment, adherence decreased to 77.9% (P < .001). Looking at drugs for each condition, nonadherence ranged from 15.6% to 38% (P < .001). Factors associated with an increase in nonadherence included older age, insurance type, number of medications, and comorbid conditions.

Conclusion:

Decreased adherence to medications for chronic diseases was found in the first year after breast cancer treatment. Breast cancer survivors may need additional interventions to improve their adherence to their medications for chronic conditions.

from Cancer via ola Kala on Inoreader http://ift.tt/2b5eCJ9
via IFTTT

Electronic Release of Pathology and Radiology Results to Patients: Opinions and Experiences of Oncologists [CARE DELIVERY]

Purpose:

There is an emerging standard to provide patients rapid electronic access to elements of their medical records. Although surveys of patients generally support it, this practice is controversial among oncologists, because few empiric data are available for scenarios of potentially life-threatening conditions like cancer. We report the views of oncologists about patient electronic access to radiology and pathology results that could potentially indicate disease progression.

Methods:

Four months before oncologists were surveyed, final results of radiology/pathology reports were routinely made available to patients online through a secure portal after a 7-day, hold to provide clinicians time to review and communicate results with the patients. Mixed methods were used to assess physician attitudes and experiences toward this change.

Results:

One hundred twenty-nine oncologists were surveyed, and 82 (64%) responded. A small majority (54%) responded that the release of reports was somewhat or very beneficial for patients who received normal radiology/pathology results before discussion with a physician, but 87% said it was somewhat or very harmful for patients to receive abnormal results before discussion. Forty-nine percent reported that release of reports had a somewhat or very negative impact on communication with their patients.

Conclusion:

Almost half of oncologists reported that sharing digital radiology and pathology records had a negative impact on their communication with patients. Patient surveys in similar cancer populations would complement the physician perspective. Efforts are needed to improve consensus among oncologists and patients on how to best communicate such results in a timely fashion.

from Cancer via ola Kala on Inoreader http://ift.tt/2aC5lvv
via IFTTT

Acute, Unilateral Breast Toxicity From Gemcitabine in the Setting of Thoracic Inlet Obstruction [Case Report]

from Cancer via ola Kala on Inoreader http://ift.tt/2b5e2v7
via IFTTT

Management of Chronic Pain in Survivors of Adult Cancers: ASCO Clinical Practice Guideline Summary [Guideline Summaries]

from Cancer via ola Kala on Inoreader http://ift.tt/2aC5IGG
via IFTTT

A Multidisciplinary Approach to Larynx Cancer: One Size Does Not Fit All [COMMENTARIES]

from Cancer via ola Kala on Inoreader http://ift.tt/2b5ew4j
via IFTTT

Multidisciplinary Care of Laryngeal Cancer [Clinical Reviews]

Treatment of larynx cancer has changed dramatically over the past several years. Novel modalities of treatment have been introduced as organ preservation has been developed. In addition, new targeted therapies have appeared, and improvements in radiotherapeutic and surgical techniques have been introduced. Thus, a large variety of treatment options is increasing local control rates and overall survival; however, selecting the most appropriate treatment remains a challenging decision. This article focuses on the multidisciplinary care of early-stage and locally advanced larynx cancer and attempts to sum up different approaches. Moreover, it reviews state-of-the-art treatment in larynx preservation, which has been consolidated in recent years.

from Cancer via ola Kala on Inoreader http://ift.tt/2aC4YBa
via IFTTT

Management of Depression in Patients With Cancer: A Clinical Practice Guideline [Guideline Summaries]

Purpose:

This report updates the Cancer Care Ontario Program in Evidence-Based Care guideline for the management of depression in adult patients with cancer. This guideline covers pharmacologic, psychological, and collaborative care interventions, with a focus on integrating practical management tools to assist clinicians in delivering appropriate treatments for depression in patients with cancer.

Methods:

Recommendations were developed by synthesizing information from extant guidelines and reviews and searching for randomized controlled trials from the date of database inception (1964 for MEDLINE and 1974 for EMBASE) to January 2015. Quality assessment of guidelines and systematic reviews were conducted by using the Appraisal of Guidelines for Research and Evaluation II (AGREE II), Assessment of Multiple Systematic Reviews (AMSTAR), and Cochrane Risk of Bias tools. Final recommendations were developed through a standardized Program in Evidence-Based Care multidisciplinary expert and knowledge user review process.

Results:

Two high-quality relevant clinical practice guidelines, eight pharmacologic trials, nine psychological trials, and eight collaborative care intervention trials composed the evidence base upon which the recommendations were developed. Eight specific recommendations were made to establish a standard of care for the management of depression in patients with cancer. The recommendations and practical management tools were reviewed as being well organized and helpful, although systemic barriers to implementation were identified.

Conclusion:

This updated guideline supports the previous general recommendation that patients with cancer who have depression may benefit from psychological and/or pharmacologic interventions, without evidence for the superiority of any specific treatment over another. New recommendations for a collaborative care model that incorporates a stepped care approach suggest that multidisciplinary mental health care restructuring may be required for optimal management of depression.

from Cancer via ola Kala on Inoreader http://ift.tt/2b5eh9t
via IFTTT

Stereotactic Radiosurgery for Brain Metastases: More Work to Be Done [COMMENTARIES]

from Cancer via ola Kala on Inoreader http://ift.tt/2aC71oI
via IFTTT

Searching for Synergy: Combining Drugs and Stereotactic Radiosurgery for the Treatment of Brain Metastases [COMMENTARIES]

from Cancer via ola Kala on Inoreader http://ift.tt/2aC5AqF
via IFTTT

Stereotactic Radiosurgery for Treatment of Brain Metastases [Clinical Reviews]

Brain metastases are the most common intracranial malignancy. Incidence of brain metastases has risen as systemic therapies have improved and patients with metastatic disease live longer. Whole-brain radiation therapy, for many years, has been the standard treatment approach. Stereotactic radiosurgery has become an increasingly popular option because of its relatively short, convenient, and noninvasive treatment course. Although recently published data have renewed interest in use of whole-brain radiation therapy or systemic therapies for control of micrometastatic disease, stereotactic radiosurgery continues to be an important modality, capable of delivering ablative doses of radiation for long-term control of macroscopic disease. The purpose of this review is to explore the different paradigms for incorporation of stereotactic radiosurgery into management of brain metastases. Current uses for stereotactic radiosurgery include delivery as a boost with whole-brain radiation therapy; alone for patients with a limited number of brain metastases; in pre- or postoperative settings; and in combination with systemic, targeted, and immune-based therapies. Mature prospective data on use of stereotactic radiosurgery in combination with whole-brain radiation therapy is available; however, prospective, randomized data on stereotactic radiosurgery for patients with a greater number of brain metastases, its use in pre- and postoperative settings, and its use in combination with systemic therapies are limited. Data from ongoing and future studies are needed to define the appropriate use of stereotactic radiosurgery in these settings.

from Cancer via ola Kala on Inoreader http://ift.tt/2aC5rDk
via IFTTT

Better Screening Using Big Data [Editorial]

from Cancer via ola Kala on Inoreader http://ift.tt/2b5dQMq
via IFTTT

Functional Organ Preservation in Larynx Cancer: A Continuing Debate [COMMENTARIES]

from Cancer via ola Kala on Inoreader http://ift.tt/2b5eaL3
via IFTTT

Screening for Pancreatic Adenocarcinoma Using Signals From Web Search Logs: Feasibility Study and Results [FOCUS ON QUALITY]

Introduction:

People's online activities can yield clues about their emerging health conditions. We performed an intensive study to explore the feasibility of using anonymized Web query logs to screen for the emergence of pancreatic adenocarcinoma. The methods used statistical analyses of large-scale anonymized search logs considering the symptom queries from millions of people, with the potential application of warning individual searchers about the value of seeking attention from health care professionals.

Methods:

We identified searchers in logs of online search activity who issued special queries that are suggestive of a recent diagnosis of pancreatic adenocarcinoma. We then went back many months before these landmark queries were made, to examine patterns of symptoms, which were expressed as searches about concerning symptoms. We built statistical classifiers that predicted the future appearance of the landmark queries based on patterns of signals seen in search logs.

Results:

We found that signals about patterns of queries in search logs can predict the future appearance of queries that are highly suggestive of a diagnosis of pancreatic adenocarcinoma. We showed specifically that we can identify 5% to 15% of cases, while preserving extremely low false-positive rates (0.00001 to 0.0001).

Conclusion:

Signals in search logs show the possibilities of predicting a forthcoming diagnosis of pancreatic adenocarcinoma from combinations of subtle temporal signals revealed in the queries of searchers.

from Cancer via ola Kala on Inoreader http://ift.tt/2b5e8CY
via IFTTT

Adjuvant Radiation in the TORS Era – Is There a Benefit to Omitting the Tumor Bed?

Publication date: Available online 9 August 2016
Source:Practical Radiation Oncology
Author(s): Stanislav Lazarev, Blagoja Todorov, James Tam, Vishal Gupta, Brett A. Miles, Nancy Lee, Richard L. Bakst
PurposeTrans-oral robotic surgery (TORS) followed by adjuvant radiotherapy (RT) is becoming popular in treating node-positive tonsillar squamous cell carcinoma (SCC). One potential benefit is eliminating irradiation of the primary site when the tumor is widely resected, and targeting the neck only. This study assessed whether omitting the tumor bed provides any dosimetric or clinical advantage.Methods and MaterialsWe identified 21 patients with primary tonsillar SSC that were treated with TORS followed by RT to the ipsilateral neck and primary site. We subsequently re-planned each case to allow target coverage to the neck only, excluding the tumor bed. For each case, we created 2 plans: neck only (NO) and neck plus primary (N+P). Additionally, we identified patients (n=7) with primary SSC tonsil who did receive neck only irradiation in order to compare their dosimetry and toxicity profile with those treated to both the primary site and ipsilateral neck. Contralateral neck radiation was not administered in any of these cases.ResultsDespite excluding the primary site in the NO plans, the mean dose to the tumor bed was high - 53.9Gy. The only significant differences in omitting the primary site were lower doses to the oral cavity, 29.8Gy in NO plan versus 34.6Gy in N+P plan, p=0.002, and superior constrictors, 42.9Gy in NO plan versus 46.1Gy in N+P plan, p=0.01. No appreciable differences in toxicities were noted in the limited cohort treated with neck only irradiation.ConclusionsSparing the primary site after TORS in node-positive tonsillar SSC does not appear to provide any significant dosimetric or clinical advantage. Furthermore, the tumor bed receives a significant but potentially sub-therapeutic dose, limiting options for irradiation in a salvage setting. At this time, we do not recommend omitting the tumor bed from the radiation target volume following TORS.



from Cancer via ola Kala on Inoreader http://ift.tt/2aMDnhX
via IFTTT

Basic Principles of Sports Nutrition

Abstract

Proper nutrition is a key component in the preparation and training of the competitive athlete. The dietary recommendations for sports nutrition are surprisingly conventional, similar to that for the prevention of chronic disease (such as cancer, diabetes, stroke, hypertension, and cardiovascular disease). Few specialized supplements are required above a well-balanced diet of sufficient protein and carbohydrate. Total caloric requirements, macronutrient composition, and need for electrolyte/micronutrient repletion may vary from one sport to another (and between various positions within a single sport). The type and duration of the sporting event affect the utilization of energy systems, substrate availability, and the training adaptations required to optimize athleticism. Undernutrition, dehydration, and electrolyte abnormalities can reduce cognition, endurance, thermoregulation, overall performance, and recovery. A properly designed dietary program throughout training, competition, and the off-season should benefit and help protect both the recreational and the elite athlete.

from Cancer via ola Kala on Inoreader http://ift.tt/2aX7u16
via IFTTT

Overall survival of cancer patients with serum lactate dehydrogenase greater than 1000 IU/L

Abstract

High level of serum lactate dehydrogenase (LDH) is a well-known poor prognostic factor in patients with malignancies. However, there was no data on overall survival (OS) in cancer patients with serum LDH level > 1000 IU/L, and the prognostic value of the changes in LDH over time for OS had not been reported. Clinical data of 311 cancer patients with metastatic disease with serum LDH >1000 IU/L (four times upper limit of normal) admitted consecutively to a single center were reviewed in this retrospective study. LDH level ranged from 1002 to 8235 U/L with a mean of 1689 U/L. The median OS was 1.7 months (95 % CI: 1.4–2.0). About half of patients (n = 163, 52 %) died within 2 months with the median OS of 0.5 months (95 % CI: 0.3–0.7). Only 173 patients were indicated for salvage treatment. Fifty-one patients' serum LDH level decreased to normal at 2 months following chemotherapy; OS was significantly longer in these patients (22.6 months, 95 % CI: 10.9–34.3, p < 0.001) compared to those with persistently abnormal serum LDH at 2 months (4.0 months, 95 % CI: 3.4–4.6). The independent factors that increased the death risk were ECOG performance status 3–4 (HR: 2.05, 95 % CI: 1.42–2.97, p < 0.001), supportive care only (HR: 2.91, 95 % CI: 2.06–4.10, p < 0.001), and persistently abnormal serum LDH at 2 months (HR: 2.72, 95 % CI: 1.67–4.42, p < 0.001). In conclusion, serum LDH level > 1000 IU/L predicted a terminal stage in metastatic cancer patients. OS was significantly prolonged in patients indicated for effective palliative treatment and LDH level decreased to normal at 2 months.

from Cancer via ola Kala on Inoreader http://ift.tt/2aBU9iD
via IFTTT

Experimental verification of a predicted novel microRNA located in human PIK3CA gene with a potential oncogenic function in colorectal cancer

Abstract

PI3K/AKT signaling is involved in cell survival, proliferation, and migration. In this pathway, PI3Kα enzyme is composed of a regulatory protein encoded by p85 gene and a catalytic protein encoded by PIK3CA gene. Human PIK3CA locus is amplified in several cancers including lung and colorectal cancer (CRC). Therefore, microRNAs (miRNAs) that are encoded within the PIK3CA gene might have a role in cancer development. Here, we report a novel microRNA named PIK3CA-miR1 (EBI accession no. LN626315), which is located within PIK3CA gene. A DNA segment corresponding to PIK3CA-premir1 sequence was transfected in human cell lines that resulted in generation of mature exogenous PIK3CA-miR1. Following the overexpression of PIK3CA-miR1, its predicted target genes (APPL1 and TrkC) were significantly downregulated in the CRC-originated HCT116 and SW480 cell lines, detected by qRT-PCR. Then, dual luciferase assay supported the interaction of PIK3CA-miR1 with APPL1 and TrkC transcripts. Endogenous PIK3CA-miR1 expression was also detected in several cell lines (highly in HCT116 and SW480) and highly in CRC specimens. Consistently, overexpression of PIK3CA-premir1 in HCT116 and SW480 cells resulted in significant reduction of the sub-G1 cell distribution and apoptotic cell rate, as detected by flowcytometry, and resulted in increased cell proliferation, as detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. PIK3CA-miR1 overexpression also resulted in Wnt signaling upregulation detected by Top/Fop assay. Overall, accumulative evidences indicated the presence of a bona fide novel onco-miRNA encoded within the PIK3CA oncogene, which is highly expressed in colorectal cancer and has a survival effect in CRC-originated cells.

from Cancer via ola Kala on Inoreader http://ift.tt/2aBUxgW
via IFTTT

In silico analysis of novel mutations in maple syrup urine disease patients from Iran

Abstract

Maple Syrup Urine Disease (MSUD) is a rare autosomal recessive disorder of branched-chain amino acid (BCAA) metabolism. The disease is mainly caused by mutations either in the BCKDHA, BCKDHB, DBT or DLD genes encoding components of the E1α, E1β, E2 and E3 subunits of branched-chain α-keto acid dehydrogenase complex (BCKDC), respectively. BCKDC is a mitochondrial enzyme which is responsible for the normal breakdown of BCAA. The rate of consanguineous marriage in Iran is 38.6 %, so the prevalence of autosomal recessive disorders is higher in comparison to other countries. Consanguinity increases the chance of the presence of pathogenic mutations in a homoallelic state. This phenomenon has made homozygosity mapping a powerful tool for finding the probable causative gene in heterogeneous disorders like IEM (Inborn Errors of Metabolism). In this study, two sets of multiplex polymorphic STR (Short Tandem Repeat) markers linked to the above-mentioned genes were selected to identify the probable pathogenic gene in the studied families. The families who showed a homozygous haplotype for the STR markers of the BCKDHB gene were subsequently sequenced. Four novel mutations including c.633 + 1G > A, c.988G > A, c.833_834insCAC, and a homozygous deletion of whole exon 3 c. (274 + 1_275–1) _(343 + 1_344–1), as well as one recently reported (c. 508G > T) mutation have been identified. Interestingly, three families shared a common haplotype structure along with the c. 508G > T mutation. Also, four other families revealed another similar haplotype with c.988G > A mutation. Founder effect can be a suggestive mechanism for the disease. Additionally, structural models of MSUD mutations have been performed to predict the pathogenesis of the newly identified variants.

from Cancer via ola Kala on Inoreader http://ift.tt/2bgGY6D
via IFTTT

Ectopic expression of MCAM/MUC18 increases in vitro motility and invasiveness, but decreases in vivo tumorigenesis and metastasis of a mouse melanoma K1735-9 subline in a syngeneic mouse model

Abstract

Ectopic expression of MCAM/MUC18, a cell adhesion molecule in the immunoglobulin-like gene superfamily, induces two moMCAM/MUC18-minus, non-metastatic mouse melanoma K1735 sublines, K3 (tumor⁺/met^low) and K10 (tumor⁻/met^low), to metastasize to lungs in a syngeneic C3H mouse model. In this report, we extended investigation of effects of moMCAM/MUC18 expression on tumorigenesis and metastasis in another lowly metastatic, however highly tumorigenic moMCAM/MUC18-minus mouse melanoma K1735 subline, K9 (tumor⁺⁺⁺/met^low). We transfected this subline with the moMCAM/MUC18 cDNA, selected for G418-resistant clones with different expression levels of moMCAM/MUC18, and used them for testing effects of MCAM/MUC18 expression on in vitro growth rate, motility, and invasiveness, in vivo subcutaneous tumor growth, and pulmonary metastasis in syngeneic C3H brown mice. Similar to K3 and K10 cells, increased expression of MCAM/MUC18 in K9 cells did not significantly affect in vitro growth rate, but increased in vitro motility and invasiveness. Surprisingly, increased expression of MCAM/MUC18 in K9 cells decreased their induction of tumorigenesis and suppressed their establishment of pulmonary nodules in syngeneic C3H brown mice. We concluded that increased MCAM/MUC18 expression in K9 subline increased in vitro epithelial-to-mesenchymal transition; however, it suppressed in vivo tumorigenicity and metastasis. Thus MCAM/MUC18 acts as a tumor and metastasis suppressor for the K9 subline, different from its role in other K1735 sublines, K3 and K10. Different intrinsic co-factors in different K1735 sublines, which modulate the functions of MCAM/MUC18 in the cells that interact differently to the tumor microenvironment, may render sublines manifest differently in tumorigenicity and metastasis in vivo.

from Cancer via ola Kala on Inoreader http://ift.tt/2aLXCwp
via IFTTT

Receipt of vaginal brachytherapy is associated with improved survival in women with stage I endometrioid adenocarcinoma of the uterus: A National Cancer Data Base study

BACKGROUND

Randomized controlled trials have consistently shown that the use of postoperative radiotherapy (RT) for stage I endometrial cancer leads to a reduction in the incidence of pelvic recurrences without a corresponding reduction in overall mortality. It was hypothesized that a reduction in mortality associated with the receipt of RT could be identified in a large data set with greater statistical power.

METHODS

Women with surgically staged IA or IB endometrial adenocarcinoma who were treated with total hysterectomy between 2003 and 2011 were identified in the National Cancer Data Base. Chi-square tests and multivariate logistic regression were performed to analyze factors associated with the treatment type. A survival analysis was performed with log-rank testing, Cox proportional hazards regression, and Kaplan-Meier estimates.

RESULTS

A total of 44,309 eligible women were identified (33,380 at stage IA and 10,929 at stage IB): 88.4% of the women with stage IA tumors and 51.6% of the women with stage IB tumors received no RT. Older age, comorbid disease, a higher histologic grade, and a larger tumor size were independently associated with an increase in mortality. The receipt of vaginal brachytherapy (VB) was independently associated with a reduction in mortality for both stage IA disease (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.67-0.97) and stage IB disease (HR, 0.62; 95% CI, 0.51-0.74).

CONCLUSIONS

Analyses of this large database support the utility of postoperative VB for many women with stage I endometrial cancer. Unfortunately, RT appears to be underused in this population. Greater adherence to consensus guidelines may lead to improved outcomes. Cancer 2016. © 2016 American Cancer Society.

from Cancer via ola Kala on Inoreader http://ift.tt/2bg9Jle
via IFTTT

Distinguishing malignant and benign renal masses with composite models and nomograms: A systematic review and meta-analysis of clinically localized renal masses suspicious for malignancy

Solid renal masses and cystic lesions with solid components are suspicious for renal cell carcinoma. Without an effective screening test, composite models and nomograms rely on patient and tumor characteristics to stratify the risk of benign disease versus malignant disease. To guide decisions about the use of renal mass sampling or excision, a systematic review and meta-analysis of the ability of composite models to predict the likelihood of malignancy on the basis of preoperative clinical variables was performed. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from January 1, 1997, through May 1, 2015, according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement. Composite models necessarily included imaging results and at least 1 element from the following to be compared with surgical pathology: demographic characteristics, clinical characteristics, and blood or urine tests. Two independent reviewers screened citations and extracted data. Quality Assessment Tool for Diagnostic Accuracy Studies 2 was used to assess the risk of bias. The strength of evidence was graded with the scheme recommended by Methods Guide for Effectiveness and Comparative Effectiveness Reviews. Twenty studies (12,149 patients) were included in this review. The only significant predictors of malignancy in the composite models were tumor size (effect size, 1.33-fold increased risk per centimeter; 95% confidence interval [CI], 1.22-1.43) and male sex (effect size, 2.71; 95% CI, 2.39-3.02). The results were inconclusive or not significant for tumor characteristics, age, body mass index, and incidental presentation. In conclusion, composite models currently have a limited ability to distinguish malignant renal masses from benign renal masses, with increased tumor size and male sex associated with malignancy. Cancer 2016. © 2016 American Cancer Society.

from Cancer via ola Kala on Inoreader http://ift.tt/2aMmIHw
via IFTTT

Frequency, predictors, and outcomes of urine drug testing among patients with advanced cancer on chronic opioid therapy at an outpatient supportive care clinic

BACKGROUND

Data are limited on the use and outcomes of urine drug tests (UDTs) among patients with advanced cancer. The main objective of this study was to determine the factors associated with UDT ordering and results in outpatients with advanced cancer.

METHODS

A retrospective chart review was conducted of 1058 patients who attended an outpatient supportive care clinic from March 2014 to November 2015. Sixty-one patients who were receiving chronic opioid therapy and underwent UDTs were identified. A control group of 120 patients who did not undergo UDTs was selected for comparison.

RESULTS

Sixty-one of 1058 patients (6%) underwent UDTs, and 33 of 61 patients (54%) had abnormal results. Multivariate analysis indicated that the odds ratio for UDT ordering was 3.9 in patients who had positive Cut Down, Annoyed, Guilty, and Eye Opener (CAGE) questionnaire results (P = .002), 4.41 in patients aged < 45 years (P < .001), 5.58 in patients who had moderate-to-severe pain (Edmonton Symptom Assessment Scale pain scores ≥4; P < .001), 0.27 in patients with advanced-stage cancer, (P = .008), and 0.25 in patients who had moderate-to-severe fatigue (P = .001). Among 52 abnormal UDT results in 33 patients, the most common opioid findings were prescribed opioids absent in urine (14 of 52 tests; 27%) and unprescribed opioids in urine (13 of 52 tests; 25%).

CONCLUSIONS

UDTs were used infrequently among outpatients with advanced cancer who were receiving chronic opioid therapy. Younger age, positive CAGE questionnaire results, early stage cancer or no evidence of disease status, higher pain intensity, and lower fatigue scores were significant predictors of UDT ordering. More than 50% of UDT results were abnormal. More research is necessary to better characterize aberrant opioid use in patients with advanced cancer. Cancer 2016. © 2016 American Cancer Society.

from Cancer via ola Kala on Inoreader http://ift.tt/2bgaomB
via IFTTT

Intensive treatment and survival outcomes in NUT midline carcinoma of the head and neck

BACKGROUND

NUT midline carcinoma is a rare and aggressive genetically characterized subtype of squamous cell carcinoma frequently arising from the head and neck. The characteristics and optimal management of head and neck NUT midline carcinoma (HNNMC) are unclear.

METHODS

A retrospective review of all known cases of HNNMC in the International NUT Midline Carcinoma Registry as of December 31, 2014, was performed. Forty-eight consecutive patients were treated from 1993 to 2014, and clinicopathologic variables and outcomes for 40 patients were available for analyses; they composed the largest HNNMC cohort studied to date. Overall survival (OS) and progression-free survival (PFS) according to patient characteristics and treatment were analyzed.

RESULTS

This study identified a 5-fold increase in the diagnosis of HNNMC from 2011 to 2014. The median age was 21.9 years (range, 0.1-81.7 years); the male and female proportions were 40% and 60%, respectively; and 86% had bromodomain containing 4–nuclear protein in testis (BRD4-NUT) fusion. The initial treatment was initial surgery with or without adjuvant chemoradiation or adjuvant radiation (56%), initial radiation with or without chemotherapy (15%), or initial chemotherapy with or without surgery or radiation (28%). The median PFS was 6.6 months (range, 4.7-8.4 months). The median OS was 9.7 months (range, 6.6-15.6 months). The 2-year PFS rate was 26% (95% confidence interval [CI], 13%-40%). The 2-year OS rate was 30% (95% CI, 16%-46%). Initial surgery with or without postoperative chemoradiation or radiation (P = .04) and complete resection with negative margins (P = .01) were significant predictors of improved OS even after adjustments for age, tumor size, and neck lymphadenopathy. Initial radiation or chemotherapy and the NUT translocation type were not associated with outcomes.

CONCLUSIONS

HNNMC portends a poor prognosis. Aggressive initial surgical resection with or without postoperative chemoradiation or radiation is associated with significantly enhanced survival. Chemotherapy or radiation alone is often inadequate. Cancer 2016. © 2016 American Cancer Society.

from Cancer via ola Kala on Inoreader http://ift.tt/2aMmGz9
via IFTTT

Gender differences in the effect of grief reactions and burnout on emotional distress among clinical oncologists

BACKGROUND

The current study was conducted to examine gender differences in the effect of grief reactions and burnout on emotional distress among clinical oncologists.

METHODS

The participants included a convenience sample of 178 oncologists from Israel (52 of whom were women) and Canada (48 of whom were women). Oncologists completed a questionnaire package that included a sociodemographic survey, the General Health Questionnaire, a burnout measure, and the Adult Oncologists Grief Questionnaire. To examine the effect of grief reactions and burnout on emotional distress while controlling for country and past depression within each gender, 2 hierarchical linear regression analyses were computed.

RESULTS

Female oncologists reported significantly more grief responses to patient death (mean, 47.72 [standard deviation (SD), 8.71] and mean, 44.53 [SD, 9.19], respectively), more emotional distress (mean, 12.41 [SD, 4.36] and mean, 10.64 [SD, 3.99], respectively), and more burnout (mean, 2.59 [SD, 1.69] and mean, 1.84 [SD, 1.5], respectively). For both genders, higher levels of grief reactions were associated with greater emotional distress among those who reported high levels of burnout (P<.001). However, for men, the association between grief reactions and emotional distress also was documented at moderate levels of burnout (P<.001).

CONCLUSIONS

Patient death is a regular part of clinical oncology. It is essential that oncologists be able to cope effectively with this aspect of their work. The findings of the current study highlight the need to take into account the cumulative stressors that oncologists contend with when designing supportive interventions. Gender differences in burnout, reactions to patient death, and emotional distress need to be addressed to ensure the best quality of life for oncologists and the best quality of care for their patients. Cancer 2016. © 2016 American Cancer Society.

from Cancer via ola Kala on Inoreader http://ift.tt/2bgan26
via IFTTT

Prognostic significance of day 14 bone marrow evaluation in adults with Philadelphia chromosome–negative acute lymphoblastic leukemia

BACKGROUND

The role of day 14 (D14) bone marrow (BM) assessment in detecting increased blasts in patients undergoing induction for acute lymphoblastic leukemia (ALL) is not well defined.

METHODS

This study evaluated 389 adolescent and adult patients with previously untreated Philadelphia chromosome–negative ALL who received frontline induction chemotherapy and for whom a D14 BM assessment was performed.

RESULTS

A D14 BM blast proportion < 10% (including blast-free aplastic BM) was observed in 319 patients (82%), 10% to 29% was observed in 31 patients (8%), and ≥30% was observed in 39 patients (10%). The composite complete remission (CR)/complete remission with inadequate platelet recovery (CRp) rates for these groups were 99.7%, 87%, and 79%, respectively. The median event-free survival (EFS) was 49, 33, and 9 months, respectively (P < .001). The median overall survival (OS) was 88, 37, and 21 months, respectively (P < .001). The D14 BM blast group was the only factor predictive for the achievement of CR/CRp (P < .001). According to a multivariate analysis, the D14 BM blast group was independently prognostic for both EFS (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.12-1.85; P = .004) and OS (HR, 1.45; 95% CI, 1.14-1.85; P = .003). However, when minimal residual disease (MRD) assessment at the time of CR was added to the model, the D14 BM blast group was no longer prognostic for EFS or OS.

CONCLUSIONS

An assessment of residual D14 BM blasts in patients with ALL is highly predictive of the achievement of CR with induction chemotherapy and of EFS and OS. However, the impact on long-term outcomes is less prognostic when an MRD assessment is also available. Cancer 2016. © 2016 American Cancer Society.

from Cancer via ola Kala on Inoreader http://ift.tt/2aMnbJJ
via IFTTT

White adipose tissue inflammation and cancer-specific survival in patients with squamous cell carcinoma of the oral tongue

BACKGROUND

Obesity is associated with increased adipose tissue in the tongue. Chronic white adipose tissue (WAT) inflammation commonly occurs in the obese. We investigated whether WAT inflammation in the tongue impacts survival in patients with squamous cell carcinoma (SCC) of the oral tongue.

METHODS

In a retrospective cohort study, patients with T1 and T2 SCC of the oral tongue who underwent curative-intent resection were included. Tongue WAT inflammation was defined by the presence of dead or dying adipocytes surrounded by macrophages forming crown-like structures. The primary and secondary endpoints were disease-specific survival (DSS) and overall survival (OS), respectively. Subgroup analyses were carried out in patients without lymph node involvement for whom adjuvant therapies were not indicated.

RESULTS

Archived tissue was available from 125 patients. The median follow-up was 55 months (range, 3-156 months). Overall, 49 of 125 patients (39%) had tongue WAT inflammation, which was associated with higher body mass index, increased tumor thickness, and vascular invasion (P < .05). The 3-year DSS rate for patients with tongue WAT inflammation was 59% (95% confidence interval [CI], 46%-76%) versus 82% (95% CI, 73%-92%) for those without inflammation. For patients without lymph node involvement for whom adjuvant therapy was not indicated (N = 70), tongue WAT inflammation was associated with shortened DSS and OS (P < .05). When adjusted for body mass index and potential prognostic covariates, the hazard ratio for DSS and OS was 5.40 (95% CI, 1.20-24.26) and 2.97 (95% CI, 1.02-8.65), respectively.

CONCLUSIONS

Tongue WAT inflammation is associated with worse DSS and OS in patients who have early stage SCC of the oral tongue. Cancer 2016. © 2016 American Cancer Society.

from Cancer via ola Kala on Inoreader http://ift.tt/2bg9xlV
via IFTTT

A propensity score matching analysis of dasatinib and nilotinib as a frontline therapy for patients with chronic myeloid leukemia in chronic phase

BACKGROUND

Both dasatinib and nilotinib are approved frontline therapy for chronic myeloid leukemia in chronic phase (CML-CP) based on randomized trials compared with imatinib. However, no head-to-head comparison of dasatinib and nilotinib has been conducted in patients with newly diagnosed CML-CP.

METHODS

The authors conducted a propensity score (PS) matched comparison of patients with CML-CP who received frontline therapy with either dasatinib (N = 102) or nilotinib (N = 104) under the respective phase 2 trials conducted in parallel.

RESULTS

PS matching resulted in 87 patients from each trial being matched for pretreatment characteristics. The 3-month BCR-ABL1/ABL1 ratio <10% rate was 93% with dasatinib and 94% with nilotinib (P = .25); the rates of major molecular response at 12 months were 77% and 85%, respectively (P = .13); and the rates of molecular response with 4.5-log reduction in the ratio at 36 months were 66% and 64%, respectively (P = .96). All other clinically relevant responses were similar between the 2 treatment cohorts. The 3-year probability of event-free survival was 89% among the patients who received dasatinib and 87% among those who received nilotinib (P = .99), and the corresponding 3-year overall survival probabilities were 99% and 93%, respectively (P = .95). No statistical difference was observed between the dasatinib and nilotinib groups in any of the other survival endpoints. The treatment discontinuation rate also was similar between the 2 cohorts (dasatinib group, 18%; nilotinib group, 19%; P = .82).

CONCLUSIONS

In a PS-matched cohort of patients with newly diagnosed CML-CP, dasatinib and nilotinib offer similar response and survival outcomes. Both drugs can be considered reasonable standard-of-care options as first-line therapy for patients with CML-CP. Cancer 2016. © 2016 American Cancer Society.

from Cancer via ola Kala on Inoreader http://ift.tt/2aMmBM1
via IFTTT

Dietary docosahexaenoic acid to eicosapentaenoic acid ratios effects on hemato-immunological and plasma biochemical parameters in silvery-black porgy ( Sparidentex hasta ) juveniles

Abstract

An 8-week feeding experiment was conducted in juvenile silvery-black porgy (Sparidentex hasta) (initial mean weight 20.1 ± 0.1 g, mean ± SD) to estimate the optimum dietary docosahexaenoic to eicosapentaenoic acid (DHA/EPA) ratio. Triplicate groups of fish (12 fish in each replicate) were kept into 15 cylindrical polyethylene tanks (250 L) at 18.7 °C and handfed by one of the five diets which formulated with graded ratios of DHA/EPA (0.2, 0.4, 0.9, 2.0, 3.3) two times daily. In the fillet and liver, DHA and DHA/EPA ratios significantly increased with increasing dietary DHA concentrations (P < 0.05). Fish fed the 0.2 DHA/EPA ratio diets had the highest hemolytic activity (P < 0.05). Plasma thiobarbituric acid reactive substance concentration, catalase activity, total antioxidant capacity, total cholesterol, and triglyceride significantly decreased with increasing dietary DHA/EPA ratios (P < 0.05). It is concluded that health status of silvery-black porgy juveniles were not influenced by dietary graded ratios of DHA/EPA.

from Cancer via ola Kala on Inoreader http://ift.tt/2b8i1v4
via IFTTT