Lack of Apparent Survival Benefit from the Use of Androgen Deprivation Therapy in Patients with High-Risk Prostate Cancer Treated with Combined External Beam Radiotherapy and Brachytherapy

Publication date: Available online 9 September 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): David D. Yang, Vinayak Muralidhar, Brandon A. Mahal, Paul L. Nguyen, Phillip M. Devlin, Martin T. King, Peter F. Orio
PurposeWhile level 1 evidence has demonstrated a survival benefit from the addition of androgen deprivation therapy (ADT) to external beam radiation therapy (EBRT) for patients with high-risk prostate cancer, the benefits of ADT with combined EBRT and brachytherapy for high-risk patients are unclear. We examined the association between ADT and overall survival in a national cohort of high-risk patients treated with EBRT with or without brachytherapy.Methods and MaterialsWe identified 46,325 men in the National Cancer Database diagnosed from 2004 through 2011 with high-risk prostate cancer (Gleason 8-10, clinical T3-4, or prostate-specific antigen >20 ng/mL) who were treated with EBRT with or without brachytherapy and ADT. Multivariable Cox regression adjusting for sociodemographic and clinicopathologic factors was used to identify the association between ADT and overall survival.ResultsMedian follow-ups were 48.6 and 59.2 months for patients treated with EBRT only and combined modality radiotherapy, respectively. ADT was associated with an improvement in overall survival for the 85.0% (39,361) of the study cohort managed with EBRT alone (adjusted hazard ratio 0.91, P=0.001) but not for patients treated with combined modality radiotherapy (adjusted hazard ratio 1.05, P=0.496), with a significant interaction (Pinteraction=0.036).ConclusionsAs opposed to the known survival benefit when ADT is given with EBRT, our results suggest that ADT may not improve survival for high-risk patients treated with combined EBRT and brachytherapy. Given the significant adverse effects of ADT, particularly long-term therapy, a randomized controlled trial of combined EBRT and brachytherapy with or without ADT for select high-risk patients using a non-inferiority design should be undertaken.

Teaser

The benefits of androgen deprivation therapy (ADT) with combined external beam radiotherapy and brachytherapy for patients with high-risk prostate cancer are unknown. Using a large, national cohort of high-risk patients, we found that ADT was associated with an improvement in overall survival for patients managed with EBRT alone but not for patients treated with combined modality radiotherapy, suggesting that ADT may not improve overall survival for select high-risk patients treated with combined modality radiotherapy.


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Transcatheter aortic valve-in-valve implantation of a CoreValve in a JenaValve prosthesis: a case report

Transcatheter aortic valve implantation has become an accepted treatment modality for inoperable or high-risk surgical patients with symptomatic severe aortic stenosis.

http://ift.tt/2gTzbvS

Knowledge About the Relation Between Tobacco and Disease and the Attitude Toward Advising the Cessation of Its Consumption Among a Group of Spanish Dental Students

Abstract

Tobacco is one of the leading causes of preventable death in the developed world. Smoking is associated with a large number of oral pathologies, such as cancer and periodontitis. Dental professionals can play a key role in preventing these health problems. The objectives of this study were (1) to analyze tobacco consumption habits among a group of Spanish dental students, and (2) to assess their knowledge, perceptions, and attitudes regarding procedures to help patients quit smoking. A cross-sectional descriptive study was carried out at the Faculty of Medicine and Dentistry of Santiago de Compostela (Galicia, Spain). Three validated questionnaires were distributed, and the obtained data was processed using SPSS. One hundred twenty out of 220 surveys were completed. Of the students, 18.3% were smokers and the average number of smoked cigarettes per day was 7.5. Tobacco dependence and the intention to give up the habit were low (Fagerström Test) and doubtful (Richmond test), respectively. The majority of students (94.2%) considered it appropriate to promote tobacco use cessation (TUC) activities. A great divergence of criteria regarding tobacco-associated pathologies was found among courses. This article provides positive data about the motivation of dental students to implement TUC strategies. Nevertheless, the usefulness of these interventions makes it necessary to modify the university curricula in order to improve the education on this issue to reduce the incidence of future health problems.

http://ift.tt/2wR38Eh

Knowledge About the Relation Between Tobacco and Disease and the Attitude Toward Advising the Cessation of Its Consumption Among a Group of Spanish Dental Students

Abstract

Tobacco is one of the leading causes of preventable death in the developed world. Smoking is associated with a large number of oral pathologies, such as cancer and periodontitis. Dental professionals can play a key role in preventing these health problems. The objectives of this study were (1) to analyze tobacco consumption habits among a group of Spanish dental students, and (2) to assess their knowledge, perceptions, and attitudes regarding procedures to help patients quit smoking. A cross-sectional descriptive study was carried out at the Faculty of Medicine and Dentistry of Santiago de Compostela (Galicia, Spain). Three validated questionnaires were distributed, and the obtained data was processed using SPSS. One hundred twenty out of 220 surveys were completed. Of the students, 18.3% were smokers and the average number of smoked cigarettes per day was 7.5. Tobacco dependence and the intention to give up the habit were low (Fagerström Test) and doubtful (Richmond test), respectively. The majority of students (94.2%) considered it appropriate to promote tobacco use cessation (TUC) activities. A great divergence of criteria regarding tobacco-associated pathologies was found among courses. This article provides positive data about the motivation of dental students to implement TUC strategies. Nevertheless, the usefulness of these interventions makes it necessary to modify the university curricula in order to improve the education on this issue to reduce the incidence of future health problems.

http://ift.tt/2wR38Eh

Atezolizumab in platinum-treated locally advanced or metastatic urothelial carcinoma: post-progression outcomes from the phase II IMvigor210 study

Abstract

BackgroundConventional criteria for tumor progression may not fully reflect the clinical benefit of immunotherapy or appropriately guide treatment decisions. The phase II IMvigor210 study demonstrated the efficacy and safety of atezolizumab, a programmed death-ligand 1–directed antibody, in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (mUC). Patients could continue atezolizumab beyond Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 progression at the investigator's discretion: this analysis assessed post-progression outcomes in these patients.Patients and methodsPatients were treated with atezolizumab 1200 mg intravenously every 3 weeks until loss of clinical benefit. Efficacy and safety outcomes in patients who experienced RECIST v1.1 progression and did, or did not, continue atezolizumab were analyzed descriptively.Results220 patients who experienced progression from the overall cohort (n = 310) were analyzed: 137 continued atezolizumab for ≥ 1 dose after progression, 19 received other systemic therapy, and 64 received no further systemic therapy. Compared with those who discontinued, patients continuing atezolizumab beyond progression were more likely to have had a baseline Eastern Cooperative Oncology Group performance status of 0 (43.1% vs 31.3%), less likely to have had baseline liver metastases (27.0% vs 41.0%), and more likely to have had an initial response to atezolizumab (responses in 11.7% vs 1.2%). Five patients (3.6%) continuing atezolizumab after progression had subsequent responses compared with baseline measurements. Median post-progression overall survival was 8.6 months in patients continuing atezolizumab, 6.8 months in those receiving another treatment, and 1.2 months in those receiving no further treatment. Atezolizumab exposure–adjusted adverse event frequencies were generally similar before and following progression.ConclusionIn this single-arm study, patients who continued atezolizumab beyond RECIST v1.1 progression derived prolonged clinical benefit without additional safety signals. Identification of patients most likely to benefit from atezolizumab beyond progression remains an important challenge in the management of mUC.ClinicalTrials.gov IDNCT02108652.

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The preliminary radiogenomics association between MR perfusion imaging parameters and genomic biomarkers, and their predictive performance of overall survival in patients with glioblastoma

Abstract

The radiogenomics association of neovascularization is important for overall survival (OS) in glioblastoma patients and remains unclear. The purpose of this study is to assess the association between MR perfusion imaging derived parameters and genomic biomarkers of glioblastoma, and to evaluate their prognostic value. This retrospective study enrolled 41 patients with newly diagnosed glioblastoma. The mean and maximal relative cerebral blood volume (rCBV) ratio (rCBV_mean and rCBV_max), derived from MR perfusion weighted imaging, of the enhancing tumor, as well as maximal rCBV ratio of peri-enhancing tumor area (rCBV_peri-tumor) were measured. The ki-67 labeling index, mammalian target of rapamycin (mTOR) activation, epidermal growth factor receptor (EGFR) amplification, isocitrate dehydrogenase (IDH) mutation and TP53 were assessed. There was a significant correlation between rCBV_max and mTOR based on Pearson's correlations with Benjamini–Hochberg adjustment for controlling false discovery rate, p = 0.047. The rCBV_peri-tumor showed significant correlation with mTOR (p = 0.0183) after adjustment of gender and EGFR status. The mean rCBV_peri-tumor value of the patients with OS shorter than 14 months was significantly higher than patients with OS longer than 14 months, p = 0.002. The rCBV_peri-tumor and age were the two strongest predictors of OS (hazard ratio = 1.29 and 1.063 respectively) by Cox regression analysis. This study showed that hemodynamic abnormalities of glioblastoma were associated with genomics activation status of mTOR-EGFR pathway, however, the radiogenomics associations are different in enhancing and peri-enhancing area of glioblastoma. The rCBV_peri-tumor has better prognostic value than genomic biomarkers alone.

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Prognostic role of progesterone receptor expression in a population-based analysis

Abstract

Purpose

The role of progesterone (PR) expression in the management of breast cancer is controversial. The aim of this study is to evaluate the characteristics and prognosis of progesterone status among breast cancers patients in a population-based analysis.

Materials and methods

Through the Tuscan Cancer Registry data on all the invasive breast cancer cases diagnosed during the period 2004–2005 in the provinces of Florence and Prato, central Italy, were retrieved. Histological reports were re-examined to obtain information on the percentage of positive tumor cells for estrogen (ER), progesterone (PR) receptors, Ki67 marker and human epidermal growth factor 2 (HER2). Information on age, stage, differentiation grade were also obtained.

Results

Out of 1487 patients, 28% had PR− breast cancer. These patients were older (p 0.006) than PR+ cancer patients, with more frequently high Ki67 (p < 0.0001), HER2 + (p < 0.0001), ER− (p < 0.0001) tumoral expression. The ER+/PR+ subtype was the most represented (n.1053), while ER−/PR+ was the most rare (n.23); 210 cases (14.1%) ER+ PR− and 201 (13.5%) ER−/PR− cases were found. Analysis of survival by the Cox proportional hazards model showed an independent prognostic value of PR expression (p < 0.0001), also when estrogen, Ki67, HER2 status and age were included. The 5-year cancer-specific survival was 82.1, 86.5, 100, 92% for ER−/PR−, ER+/PR−, ER−/PR+, ER+/PR+ subtype, respectively.

Conclusions

Our study revealed significant differences in clinicopathological characteristics among breast cancer according to PR expression and confirmed its prognostic independent role, suggesting a role of PR in the improvement of breast cancer prognostic characterization.

http://ift.tt/2xTxVzX

Multidimensional phenotyping of breast cancer cell lines to guide preclinical research

Abstract

Purpose

Cell lines are extremely useful tools in breast cancer research. Their key benefits include a high degree of control over experimental variables and reproducibility. However, the advantages must be balanced against the limitations of modelling such a complex disease in vitro. Informed selection of cell line(s) for a given experiment now requires essential knowledge about molecular and phenotypic context in the culture dish.

Methods

We performed multidimensional profiling of 36 widely used breast cancer cell lines that were cultured under standardised conditions. Flow cytometry and digital immunohistochemistry were used to compare the expression of 14 classical breast cancer biomarkers related to intrinsic molecular profiles and differentiation states: EpCAM, CD24, CD49f, CD44, ER, AR, HER2, EGFR, E-cadherin, p53, vimentin, and cytokeratins 5, 8/18 and 19.

Results

This cell-by-cell analysis revealed striking heterogeneity within cultures of individual lines that would be otherwise obscured by analysing cell homogenates, particularly amongst the triple-negative lines. High levels of p53 protein, but not RNA, were associated with somatic mutations (p = 0.008). We also identified new subgroups using the nanoString PanCancer Pathways panel (730 transcripts representing 13 canonical cancer pathways). Unsupervised clustering identified five groups: luminal/HER2, immortalised ('normal'), claudin-low and two basal clusters, distinguished mostly by baseline expression of TGF-beta and PI3-kinase pathway genes.

Conclusion

These features are compared with other published genotype and phenotype information in a user-friendly reference table to help guide selection of the most appropriate models for in vitro and in vivo studies, and as a framework for classifying new patient-derived cancer cell lines and xenografts.

http://ift.tt/2vWRydW

Role of ALDH1 in the prognosis of esophageal cancer and its relationship with tumor microenvironment

Abstract

Aldehyde dehydrogenase 1 (ALDH1) is associated with tumorigenesis, and significantly increased in cancer stem-like cells. In the present study, the role of ALDH1 in esophageal squamous cell carcinoma (ESCC) was investigated. We retrospectively analyzed the clinical outcomes of 148 ESCC and examined its correlation with ALDH1 levels. Furthermore, we preformed cellular and animal experiments to investigate the role of ALDH1 in tumor progression and microenvironment. Our data revealed that ALDH1 staining was positively linked to a higher clinical stage, higher loco-regional failure rate and shorter survival time. Furthermore, there was a positive link between ALDH1 expression and IL-6 signaling according to the data of clinical specimens and cellular experiments. Using animal model, ALDH1-positive tumors were associated with aggressive tumor growth, increased IL-6, augmented epithelial-mesenchymal transition (EMT), and activation of myeloid-derived suppressor cells (MDSCs). Blockade of COX-2 attenuated the aggressive tumor growth of ALDH1-positive cancer cells. In conclusion, our findings suggested that ALDH1 played an important role in tumor aggressiveness and associated with a tumor-promoting microenvironment in esophageal cancer. Directly targeting ALDH1 or using a COX-2 inhibitor could be a promising strategy for the treatment of ESCC. This article is protected by copyright. All rights reserved

http://ift.tt/2vLPQHZ

Identifying the subtypes of cancer-related fatigue: results from the population-based PROFILES registry

Abstract

Purpose

Little research has been done to identify possible cancer-related fatigue (CRF) subtypes and to classify cancer survivors accordingly. We aimed to identify CRF subtypes in a large population-based sample of (long term) stage I–III colorectal cancer survivors. We also identified factors associated with the CRF subtypes.

Methods

Respondents completed the Multidimensional Fatigue Inventory and other validated questionnaires on anxiety and reduced positive affect (anhedonia), sleep quality, and lifestyle factors (body mass index and physical activity). Latent class analysis was used to derive the CRF subtypes. Factors associated with the derived CRF subtypes were determined with multinomial logistic regression.

Results

Three CRF classes were identified: class 1 (no fatigue and distress, n = 644, 56%), class 2 (low fatigue, moderate distress, n = 256, 22%), and class 3 (high fatigue, moderate distress, n = 256, 22%). Multinomial logistic regression results show that survivors in class 3 were more likely to be female, were treated with radiotherapy, have comorbid diabetes mellitus, and be overweight/obese than survivors in class 1 (reference). Survivors in classes 2 and 3 were also more likely to have comorbid heart condition, report poorer sleep quality, experience anhedonia, and report more anxiety symptoms when compared with survivors in class 1.

Conclusions

Three distinct classes of CRF were identified which could be differentiated with sleep quality, anxiety, anhedonia, and lifestyle factors.

Implications for cancer survivors

The identification of CRF subtypes with distinct characteristics suggests that interventions should be targeted to the CRF subtype.

http://ift.tt/2xVpx3F

Beyond availability: the importance of routine videolaryngoscopy and institution-based rescue methods of difficult videolaryngoscopy

Editor—We appreciate the fabulous work of Cook and Kelly on the national survey of videolaryngoscopy (VL) in the UK.¹ According to the Difficult Airway Society's 2015 guidelines² videolaryngoscopes should be immediately available at all times and all anaesthetists should be trained and skilled in their use. We are glad to see the main finding that VL is available in >90% of UK hospital, though only one in seven hospitals have VL available in all relevant clinical areas. Beyond the availability of videolaryngoscopes, whether to be skilled in VL remains an important issue.

http://ift.tt/2wfZylu

Lack of benefit of near-infrared spectroscopy monitoring for improving patient outcomes. Case closed?

Near-infrared spectroscopy (NIRS) monitoring of regional cerebral oxygen saturation (rSco2) during cardiac surgery has been available to clinicians for more than three decades.¹² This monitoring is attractive because it is non-invasive, requires minimal user technical expertise, provides an intuitively important end point (oxygenation of the superficial cerebral cortex), and has a continuous output. As a result of these features, NIRS monitoring overcomes many of the limitations of existing monitors for judging adequacy of cerebral perfusion during surgery [(particularly, throughout cardiopulmonary bypass (CPB)], such as electroencephalography, transcranial Doppler monitoring, and jugular bulb venous oxygen saturation. Early reports showing the value of bilateral rSco2 monitoring for early detection of CPB oxygenator malfunction, arterial or venous cannula malposition, and occult aortic dissection, in addition to utility during aortic arch surgery, fuelled enthusiasm for its adoption in cardiac surgery.² This enthusiasm was broadened with publication of non-randomized, observational studies showing a link between reduction from baseline rSco2 (i.e. 'desaturations') during CPB and a variety of neurological end points, including postoperative cognition dysfunction (POCD) and stroke.² Interpretation of these data, however, are confounded by many methodological limitations.

http://ift.tt/2wPI3M7

Response to: Go/no-go decision in anaesthesia: wide variation in risk tolerance amongst anaesthetists

Editor—The work by Greig and colleagues¹ brings to light conflicting organizational and management practices for the operating theatre. A majority of the confusion and tension in this high-pressure environment can be traced back to the fundamental misunderstanding of high-reliability organizations (HRO) and ultra-safe systems (USS). In fact, the authors state that "health care providers aspire to become high-reliability organizations, but this practice contrasts with existing high-reliability organizations, such as aviation, where decision-making aids and standardized operating procedures are widely used."¹ However, the aviation industry is predominantly an ultra-safe system, not a high-reliability organization.

http://ift.tt/2wgLGr1

Can predicting transfusion in cardiac surgery help patients?

In this issue of the British Journal of Anaesthesia, Klein and colleagues¹ describe the ACTA-PORT, a new score for predicting the risk of one or more red blood cell transfusions in patients undergoing cardiac surgery. The authors' desire to provide a simple, accurate tool to help predict the risk of transfusion in patients undergoing cardiac surgery is commendable, but does it help our patients?

http://ift.tt/2wgh1tP

Influence of deep neuromuscular block on the surgeonś assessment of surgical conditions during laparotomy: a randomized controlled double blinded trial with rocuronium and sugammadex

Abstract

Background. During laparotomy, surgeons may experience difficult surgical conditions if the patient's abdominal wall or diaphragm is tense. Deep neuromuscular block (NMB), defined as a post-tetanic-count (PTC) between 0-1, paralyses the abdominal wall muscles and the diaphragm. We hypothesized that deep NMB (PTC 0-1) would improve subjective ratings of surgical conditions during upper laparotomy as compared with standard NMB.Methods. This was a double blinded, randomized study. A total of 128 patients undergoing elective upper laparotomy were randomized to either continuous deep NMB (infusion of rocuronium 2 mg ml⁻¹) or standard NMB (bolus of rocuronium 10 mg or increased depth of anaesthesia). Surgical conditions were evaluated using a 5-point subjective rating scale (1: extremely poor, 5: optimal) every 30 min. Primary outcome was the average of scores for a patient's surgical conditions. Other outcomes were surgical rating score during fascial closure, episodes of a need to optimize surgical conditions, occurrence of wound dehiscence, and wound infection.Results. Deep compared with standard NMB resulted in better ratings of surgical conditions; median 4.75 (range 3–5) compared with 4.00 (range 1–5) (P<0.001), respectively. Deep compared with standard NMB resulted in better ratings of surgical conditions during fascial closure (P<0.001), fewer episodes of need to optimize surgical conditions (P<0.001), and fewer incidents with sudden movements (P<0.001). No differences in operating time, occurrence of wound infection, and wound dehiscence were found.Conclusions. Deep NMB compared with standard NMB resulted in better subjective ratings of surgical conditions during laparotomy.Clinical trial registration: NCT02140593.

http://ift.tt/2wQrFev

Viscoelastometric testing, fibrinogen and transfusion during post-partum haemorrhage

Editor—Many readers will recognize the pleasure of a new pair of glasses (Fig. 1). They are perfectly tailored to our own visual defect, and wearing them gives one a feeling of clarity and brightness that is comparable with opening the curtains after a good night's sleep. In an era of evidence-based medicine, should we question the evidence base for eyeglasses? Might this be unnecessary when there is a palpable association between a specific intervention and an intended outcome such that we are easily convinced of the causal nature of that association? There will certainly be an effect of using viscoelastometric testing on plasma transfusion if practice changes from giving plasma 'blindly' to giving plasma based on the coagulation testing. The real question is whether this change in practice will lead to better outcomes. In this issue of the BritishJournalof Anaesthesia, Collins and colleagues¹² provide new information on monitoring and managing haemostasis in patients with post-partum haemorrhage.

http://ift.tt/2wgh1dj

Videolaryngoscopy and obstetric anaesthesia

Editor—We congratulate Professor Cook and Dr Kelly on their important national survey of videolaryngoscopy in the UK.¹ They highlighted that while videolaryngoscopes (VLs) are widely available in main operating theatres, availability in other areas where tracheal intubation is undertaken is much lower, being around only 50% of intensive care units and obstetric theatres. We would suggest that this figure is a particular concern to obstetric anaesthesia, where the risk of failed intubation is greater than the general population. In 2011, we conducted a national Obstetric Anaesthetists' Association approved survey of the availability of VLs in UK obstetric units. This survey (response rate 72%) found that only 42% of obstetric units had a dedicated VL with widespread variation in the type of device available.²

http://ift.tt/2wgrPYY

Theseus, the Labyrinth, and the Minotaur of anaesthetic-induced developmental neurotoxicity

When Theseus set sail to slay the mighty Minotaur, he likely spared a thought for the difficulty in navigating the Labyrinth that surrounded his foe. The search for therapies for anaesthetic-induced developmental neurotoxicity shares a similar mythical context. In our version of these events, Prince Theseus is the cure (potentially played by dexmedetomidine), the Minotaur is sevoflurane-induced neurotoxicity and the Labyrinth (a maze of confounding factors) is represented by physiological aberrations. In this issue of the British Journal of Anaesthesia, two reports¹² appear to arrive at contradictory conclusions regarding the success of dexmedetomidine in combating sevoflurane-induced developmental neurotoxicity in neonatal rat pups. The two research teams are to be congratulated for reporting the results in a manner that enables the reader to appreciate the entire gamut from protection against organ toxicity to toxicity to the entire organism because of the clarity and detail in their reports. However, the physiological derangements observed in these studies, and their contradictory findings, lead to labyrinthine interpretation. Readers should also refer to the accompanying editorial on the same studies by Vutskits and Sall³ when considering these issues.

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In the September BJA…

This issue of the BJA contains a special section on anaesthetic neurotoxicity and neuroplasticity following a call for papers associated with the Second BJA Seminar on Neurotoxicity and Neuroplasticity held in June 2016 at Churchill House in London. The main issue includes a number of articles relevant to bleeding, transfusion and coagulation in cardiac surgery, postpartum haemorrhage, and liver transplantation, as well as important contributions on airway management.

http://ift.tt/2wQCTjg

Anaesthesia-induced developmental neurotoxicity: reality or fiction?

As animal evidence continues to mount, we face a real dilemma regarding the clinical relevance of anaesthesia-induced developmental neurotoxicity. In December 2016, the US Food and Drug Administration (FDA) issued an announcement stating that commonly used general anaesthetics could potentially be detrimental to very young and rapidly developing brains. This announcement was based on an extensive body of animal research.^1–24 Now we must grapple with the FDA's official recommendation that potential risks should be balanced with the benefits of appropriate anaesthesia in young children. More importantly, as we deal with the official expectation that potential risks should be discussed with families and heath-care providers, we are reminded how crucial it is to deepen our understanding of the pertinent mechanisms and potential long-lasting behavioural outcomes relating to the exposure of the young brain to anaesthesia.

http://ift.tt/2wgvAhi

Effects of propofol and surgery on neuropathology and cognition in the 3xTgAD Alzheimer transgenic mouse model

Abstract

Background. Previous work suggests that anaesthesia and surgery amplify the pathology and cognitive impairment of animals made vulnerable via age or specific transgenes. We hypothesized that surgery under propofol anaesthesia, a widely used i.v. general anaesthetic, has minimal delayed cognitive and neuroinflammatory sequelae in a vulnerable mouse transgenic model.Methods. We conducted caecal ligation and excision surgery in cognitively presymptomatic (11-month-old) 3xTgAD mice under i.p. propofol anaesthesia. Age-matched 3xTgAD control mice received vehicle or propofol without surgery. Morris water maze testing was conducted 3 and 15 weeks later. Brains were examined with quantitative immunohistochemistry for amyloid β plaques, tau pathology, and microglial activation. Acute changes in neuroinflammatory cytokines were assessed in separate cohorts at 6 h.Results. We detected no significant differences between groups in escape latencies at either 3 or 15 weeks, but detected a significant effect of surgery in the probe test at both 3 and 15 weeks. Spatial working memory was unaffected at 16 weeks in any group. No effects of either propofol alone or propofol with surgery were detected on plaque formation, tau aggregates, or neuroinflammation. Acute biochemical assays detected no effects in brain interleukin-10 or interleukin-6 concentrations.Conclusions. Surgery in a vulnerable transgenic mouse under propofol anaesthesia was associated with minimal to no changes in short- and long-term behaviour and no changes in neuropathology. This suggests that propofol anaesthesia is associated with better cognitive outcomes in the aged, vulnerable brain compared with inhalation anaesthesia.

http://ift.tt/2wgKfZG

Perioperative goal-directed therapy with uncalibrated pulse contour methods: impact on fluid management and postoperative outcome

Editor—The conclusions of the very recent meta-analysis by Michard and colleagues¹ in the British Journal of Anaesthesia is that the use of perioperative goal-directed therapy (GDT) with uncalibrated pulse contour (uPC) techniques is associated with a decrease in postoperative morbidity, but not associated with an increase in total fluid administration. An accompanying editorial has analysed in detail some methodological issues related to this and other systematic reviews, but has not challenged its conclusions.² In fact, the editorial expanded these conclusions claiming that this systematic review provides us with the best currently available evidence on this topic. Although these conclusions seem logical, and may even be true, a more careful examination of this meta-analysis leads me to believe that its conclusions should be very different.

http://ift.tt/2wQtIzm

Causes of sudden death of young anesthesiologists in China Response to Zhang and colleagues: Rising sudden death among anaethesiologists in China.

Editor—We read with great interest the survey results of Chinese anaesthesiologists by Zhang and colleagues.¹ The authors claimed that anaesthesiologists in China are currently suffering from work overload, and sudden death is increasing dramatically. More than 10 anaesthesiologists aged 30–45 yr had a cardiac arrest as a result of a heavy workload in China from 2013 to 2014.² The cause of death attributed to cardiac arrest is overly inclusive as one can make the argument that all demise can be eventually attributed to cardiopulmonary arrest. The causal relationship between relative 'work overload' and sudden death is lacking in pathophysiological explanation.

http://ift.tt/2wgLY13

Response to: Routine use of viscoelastic blood tests for diagnosis and treatment of coagulopathic bleeding in cardiac surgery: updated systematic review and meta-analysis

Editor—With great interest we read the systematic review and meta-analysis on the routine use of viscoelastic haemostatic assays (VHA) for diagnosis and treatment of coagulopathic bleeding in cardiac surgery published by Serraino and Murphy.¹ Significant reductions in red blood cell transfusion requirements by the use of VHA have been confirmed by previous Cochrane reviews.²³ Reducing the exposure to allogeneic blood products is a clear perioperative management goal improving patient outcome and recommended by evidence-based bleeding guidelines.⁴ Moreover, Serraino and Murphy report significant reductions in platelet transfusion and plasma transfusion (RR 0.78, 95% CI 0.66–0.93; P=0.004), which is also clinically highly relevant considering specific transfusion-associated risks. Most importantly, the authors also report a significant reduction in acute renal failure (RR 0.42, 95% CI 0.20–0.86; P=0.02). Causality cannot be identified by meta-analyses, but acute renal failure has been shown to be associated with a significant increase in long-term mortality in cardiac and noncardiac surgery.^5–8

http://ift.tt/2wQrCPR

Reply to Lucas and Vaughan: videolaryngoscopy and obstetric anaesthesia?

Editor—We thank Lucas and Vaughan for their comments on our paper.¹ Their survey correlates with our survey in 2015² in finding that approximately half of UK obstetric units have a dedicated videolaryngoscope (VL): 42% in the survey of Noblet and colleagues in 2011³ and 55% in our survey in 2013.² A survey by Hales and colleagues, also in 2014, reported that 90% of UK obstetric units have a VL, but this has yet to be published in full.⁴

http://ift.tt/2wQu7Sl

Optimal patient blood management in cardiac surgery using viscoelastic point-of-care testing Response to: Routine use of viscoelastic blood tests for diagnosis and treatment of coagulopathic bleeding in cardiac surgery: updated systematic review and meta-analysis

Editor—We read with interest the study of Serraino and Murphy¹ on routine use of point-of-care (POC) testing for diagnosis and treatment of coagulopathy in cardiac surgery patients. During cardiac surgery major blood loss is common. There is general agreement that less bleeding and optimal patient blood management are essential determinants of postoperative outcome.² The conclusion of Serraino and Murphy that POC viscoelastic testing lacks clinical effectiveness is an important negative finding, but should not disparage the significance of efficiently reducing the rate of unnecessary transfusions.

http://ift.tt/2wg9wTV

Reply to Chang: After availability, training and experience are needed

Editor—We thank Dr Chang for his kind comments.¹ It is becoming increasingly common for videolaryngoscopy to be included in guidelines for the management of difficulty during intubation, and the evidence supports this.²³ With this in mind it is a concern that one of the findings of our survey was that, although videolaryngoscopy is available in the vast majority of hospitals, it generally appears to be much less available in areas where intubation fails more frequently (obstetrics, intensive care, emergency department). We hope that this has been addressed since the time the survey was completed, but if this is not the case then we hope that the guidelines and other literature, such as our survey, may stimulate change.

http://ift.tt/2wQtKY0

Safety assessments in the avoidance of preoperative α-receptor blockade in phaeochromocytoma surgery: the pitfalls of a zero numerator

Editor—The recent observational case series reported by Groeben and colleagues¹ addressing the avoidance of preoperative α-receptor blockade in patients undergoing phaeochromocytoma surgery clearly challenges conventional thought. Their study showed that the maximal intraoperative blood pressure in non-α-blocked patients was no different than in those having received preoperative phenoxybenzamine or doxazosin therapy (185 mm Hg vs 178 mm Hg, respectively; P=0.25). In addition, there were no major complications reported – notably an absence of myocardial infarction (MI) – making this practice, at least according to the authors, seemingly "safe". Unfortunately, because of the present study's scope (i.e. an eight yr period of patient accrual) and subject matter, it is unlikely that a confirmatory study will ever be undertaken, so we are left having to rely on the authors' conclusions that "phaeochromocytoma surgery without medical pre-treatment is feasible and safe".

http://ift.tt/2wQjeQm

Viscoelastometry guided fresh frozen plasma infusion for postpartum haemorrhage: OBS2, an observational study

Abstract

Background. Postpartum haemorrhage (PPH) can be exacerbated by haemostatic failure. Based on data from trauma studies, empirical infusions of fresh frozen plasma (FFP) are often given during severe PPH if coagulation tests are unavailable. This study observed a cohort of women with moderate/severe PPH in whom FFP infusion was guided by the use of viscoelastometric point-of-care testing (VE-POCT) and clinical assessment.Methods. Women were enrolled into this observational study when blood loss was measured or suspected to be about 1000 mL. If Fibtem A5 determined by Rotem^® thromboelastometry remained >15 mm, or bleeding stopped, FFP was withheld. If Fibtem A5 was ≤15 mm and bleeding ongoing, women were randomized into an interventional study as previously reported. Clinical and laboratory outcomes were recorded.Results. The study recruited 605 women and 98% had FFP withheld. The median (25^th–75^th centile) total blood loss was 1500 (1300–2000) mL with 300 (50–545) mL occurring after enrolment. Total blood loss was >2500 mL in 40/605 (6.6%) women. RBCs were transfused in 141/605 (23.3%) patients and 11 (1.8%) received ≥4 units. At least one invasive procedure was performed in 283/605 (46.8%) women. Level 3 care was required for 10/605 (1.7%) women. No women developed clinically significant haemostatic impairment.Conclusions. Restrictive use of FFP guided by clinical assessment of bleeding and VE-POCT is feasible and did not result in clinically significant haemostatic impairment. Studies should compare the clinical and cost effectiveness of empirical FFP infusions, according to current guidelines, with targeted use of FFP based on VE-POCT.Clinical trial registration: ISRCTN46295339 (http://ift.tt/2uIJ5tt) (accessed July 24, 2017), EudraCT 2012-005511-11 (http://ift.tt/2wgwjip) (accessed July 24, 2017).

http://ift.tt/2wQYjwB

Author’s reply to Grocott: Risk of cardiac ischaemia in patients without α-receptor blockade for phaeochromocytoma surgery

Editor—We thank Prof Grocott for his comments.¹ The author questions whether the incidence of perioperative myocardial infarction in patients with phaeochromocytoma without perioperative α-receptor blockade is truly zero, without taking serial troponin measurements.

http://ift.tt/2wgLBUf

Long-term trends in incidence and survival of penile cancer in France

Publication date: October 2017
Source:Cancer Epidemiology, Volume 50, Part A
Author(s): Laetitia Daubisse-Marliac, Marc Colonna, Brigitte Trétarre, Gautier Defossez, Florence Molinié, Karine Jéhannin-Ligier, Emilie Marrer, Pascale Grosclaude
BackgroundPenile cancer is rare, and few population-based studies have described changes in time trend. This study aims to determine whether there has been an evolution in incidence and survival of penile cancer over time in France.MethodsRates of age world-standardized incidence (ASRW) and net survival (NS) between 1989 and 2011 were calculated using data from 16 French cancer registries. Time trend incidence and survival analysis were confined to the eight registries operating throughout the full period. Log-linear Poisson regression analysis was used to estimate the average annual percentage change (AAPC) in incidence rates. The incidence rate for the most recent period was also calculated from all 16 cancer registries operating during 2009–2011. Human papillomavirus (HPV) exposure was deduced from the morphological code. NS was estimated using the Pohar–Perme estimator of the net cumulative rate.ResultsNo significant change in incidence was observed between 1989 and 2011 (AAPC: 0.08%; 95%CI: −1.01%; +1.17%). The incidence increased with age. The ASRW in 16 registries operating in 2009–2011 was 0.59 per 100,000 (95%CI: 0.50–0.68). The proportion of cases potentially linked to HPV was nearly 11% and did not change significantly over time. NS decreased with age but did not change over time (around 65% at 5 years).ConclusionPenile cancer remains rare in France, but survival is still low − probably because of delays in diagnosis and limited improvements in care. International clinical trials are needed to develop care recommendations based on an adequate level of evidence.



http://ift.tt/2wOLOlU

The Roles of Vasohibin and Its Family Members: Beyond Angiogenesis Modulators.

The Roles of Vasohibin and Its Family Members: Beyond Angiogenesis Modulators.

Cancer Biol Ther. 2017 Sep 08;:0

Authors: Du H, Zhao J, Hai L, Wu J, Yi H, Shi Y

Abstract
Vasohibin-1 is an intrinsic angiogenesis inhibitor, and is expressed in endothelial cells via induction by pro-angiogenesis factors. It is known to inhibit several processes of angiogenesis, with different mechanisms from extrinsic angiogenesis inhibitors. Vasohibin-2 is mainly expressed by mononuclear cells which have been mobilized from bone marrow. It not only promotes angiogenesis, but also modulates the releases of FGF-2 and VEGF, which are the two major inducers for vasohibin1. Hypoxic environment induces the expression of hypoxia-inducible Factor 1α with a result of VEGF release nearly in all tumor cell lines and tissues. However, it has been observed that hypoxia reduces the inducible effects of VEGF on vasohibin, which indicates that a complicated mechanism exists in the angiogenesis. Vasohibin and its family members play important roles in both the physiological and pathological procedures, in contrary but complementary patterns. Furthermore, human aortic smooth muscle cells and fibroblast have also been detected to express vasohibin on a moderate to weak scale range. Recently, the results of an increasing number of studies in vivo have shown that vasohibin can also be detected in several cancers, and is associated with micro-vessel densities, histology grades, invasions, poor clinical features, metastasis, and dissemination in abdominal cavities, as well as EMT. In more recent reports, it has been confirmed that, along with being angiogenesis regulators, a variety of other roles have been associated with this family. The focus of this study was the upstream regulatory mechanisms of vasohibin expressions, and their role in regard to the downstream target proteins of vasohibin, especially in carcinoma. Vasohibin is considered to be an original angiogenesis inhibitor, and has a much broader significance in pathological processes. It can be taken as an independent prognostic factor, as well as a potential strategy for cancer therapy programs.

PMID: 28886304 [PubMed - as supplied by publisher]

http://ift.tt/2eLZlzS

Preclinical rationale for combination of crizotinib with mitomycin C for the treatment of advanced colorectal cancer.

Preclinical rationale for combination of crizotinib with mitomycin C for the treatment of advanced colorectal cancer.

Cancer Biol Ther. 2017 Sep 08;:0

Authors: Lev A, Deihimi S, Shagisultanova E, Xiu J, Lulla AR, Dicker DT, El-Deiry WS

Abstract
Colorectal cancer (CRC) is a leading cause of cancer-related deaths in the United States. We analyzed 26 MSI-High and 558 non-MSI-High CRC tumors. BRCA2 mutations were highly enriched (50%) in MSI-High CRC. Immunohistochemistry showed that BRCA2-mutated MSI-High CRC had high c-MET (64%) expression compared to BRCA-WT (17%). We hypothesized a mechanistic link between BRCA2-deficiency and c-MET overexpression and synergistic interaction between drugs that treat BRCA-deficient tumors (mitomycin C (MMC) or PARP inhibitors) and c-MET inhibitors (crizotinib). We tested CRC cell lines for sensitivity to MMC plus crizotinib or other drug combinations including PARP-inhibitors. Combined treatment of tumor cells with crizotinib and MMC led to increased apoptosis as compared to each drug alone. Additionally, combination treatment with increasing concentrations of both drugs demonstrated a synergistic anti-cancer effect (CI = 0.006-0.74). However, we found no evidence for c-MET up-regulation upon effective BRCA2 knockdown in tumor cells -/+DNA damage. Although we found no mechanistic link between BRCA2 deficiency and c-MET overexpression, c-MET is frequently overexpressed in CRC and BRCA2 is mutated especially in MSI-H CRC. The combination of crizotinib with MMC appeared synergistic regardless of MSI or BRCA2 status. Using an in-vivo CRC xenograft model we found reduced tumor growth with combined crizotinib and MMC therapy (p = 0.0088). Our preclinical results support clinical testing of the combination of MMC and crizotinib in advanced CRC. Targeting cell survival mediated by c-MET in combination with targeting DNA repair may be a reasonable strategy for therapy development in CRC or other cancers.

PMID: 28886275 [PubMed - as supplied by publisher]

http://ift.tt/2eUgSKc

Expression of SESN1, UHRF1BP1, and miR-377-3p as prognostic markers in mutated TP53 squamous cell carcinoma of the head and neck.

Expression of SESN1, UHRF1BP1, and miR-377-3p as prognostic markers in mutated TP53 squamous cell carcinoma of the head and neck.

Cancer Biol Ther. 2017 Sep 08;:0

Authors: Baroudi ME, Machiels JP, Schmitz S

Abstract
The tumor suppressor gene TP53 is the most frequently mutated gene in human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC). It represents a known transcription factor that controls different microRNAs (miRNA) and target genes involved in the regulation of cellular stress, apoptosis and response to DNA damage. We used The Cancer Genome Atlas database to investigate the difference in transcriptome and proteome levels between mutated and wild-type TP53 HPV-negative HNSCC. Using different databases and an extensive literature review, we built the transcriptional and post-transcriptional network regulated by TP53. TP53 mutation was associated with poor overall survival in 203 HPV-negative patients compared to 40 patients with TP53 wild-type tumors. Using the enrichment analysis, we found that UHRF1BP1 and SESN1 mRNA were linked to prognosis in the TP53 mutated group. This is also the case for miR-377-3p, an important miRNA regulator of SESN1. Our study shows that SESN1 mRNA, UHRF1BP11 mRNA and miRNA-377-3p levels are prognostically relevant in HPV-negative HNSCC patients. This finding may help with patient stratification and the development of potential new therapeutic targets to treat patients with HNSCC.

PMID: 28886272 [PubMed - as supplied by publisher]

http://ift.tt/2xcOCcn

MicroRNA signature in the chemoprevention of functionally-enriched stem and progenitor pools (FESPP) by Active Hexose Correlated Compound (AHCC).

MicroRNA signature in the chemoprevention of functionally-enriched stem and progenitor pools (FESPP) by Active Hexose Correlated Compound (AHCC).

Cancer Biol Ther. 2017 Sep 08;:0

Authors: Graham ÉA, Mallet JF, Jambi M, Nishioka H, Homma K, Matar C

Abstract
PURPOSE: Many breast cancer patients use natural compounds in their battle against breast cancer. Active Hexose Correlated Compound (AHCC®) is a cultured mushroom mycelium extract shown to favorably modulate the immune system and alleviate cancer burden. Cancer Stem cells (CSCs) are a subset of highly tumorigenic cancer cells that are thought to be responsible for recurrence. CSCs can be epigenetically regulated by microRNAs (miRNAs). We hypothesized that AHCC may influence CSCs by modulating tumor-suppressor or oncogenic miRNAs.
METHODS: Functionally-enriched stem and progenitor pools (FESPP) were isolated in the form of mammospheres from MDA-MB-231, MCF-7, and 4T1 cells, exposed to AHCC in both regular and primary culture from Balb/c mice, and analyzed by visual counting and flow cytometry. Cell motility was also observed in MDA-MB-231 cells. Profiling and RT-qPCR were performed to determine AHCC influence on miRNAs in MDA-MB-231 mammospheres. Additionally, Balb/c mice were orally gavaged with AHCC, and tumor growth parameters and miR-335 expression were analyzed. MDA-MB-231 cells were transfected with miR-335 and analyzed by western blot.
RESULTS: We demonstrated that AHCC reduced mammosphere growth in three cell lines and in primary culture, prevented cell migration, and upregulated miR-335 expression in MDA-MB-231 cells and mouse tumor samples. Among the differentially regulated miRNAs in CSCs, we focused on tumor suppressor miR-335, known to target extracellular matrix protein Tenascin C (TNC). TNC is involved in CSC immune evasion pathways. In MDA-MB-231, inhibition of miR-335 increased TNC protein expression.
CONCLUSIONS: These results support that AHCC limits FESPP growth, partly by targeting miRNA pathways.

PMID: 28886271 [PubMed - as supplied by publisher]

http://ift.tt/2eLZi7a

Metastasis of Esophageal Small Cell Carcinoma to the Appendix: A Case Report and Literature Review.

Metastasis of Esophageal Small Cell Carcinoma to the Appendix: A Case Report and Literature Review.

Cancer Biol Ther. 2017 Sep 08;:0

Authors: Wang Q, Zhou T, Sun H, Li B

Abstract
Primary small cell carcinoma (SCC) of the esophagus is characterized by high malignancy with a tendency to metastasize early through lymph and blood circulation. Metastasis of esophageal SCC frequently occurs to distant organs such as liver and lung. However, few cases of appendiceal metastasis have been reported. This paper first presents a pathologically confirmed case with metastasis of esophageal SCC to the appendix. This particular case highlights the importance of pathological diagnosis and provides new evidence of appendiceal metastasis from esophageal SCC.

PMID: 28886266 [PubMed - as supplied by publisher]

http://ift.tt/2jck2dr

Microvesicles releasing by oral cancer cells enhance endothelial cell angiogenesis via Shh/RhoA signaling pathway.

Microvesicles releasing by oral cancer cells enhance endothelial cell angiogenesis via Shh/RhoA signaling pathway.

Cancer Biol Ther. 2017 Sep 08;:0

Authors: Huaitong X, Yuanyong F, Yueqin T, Peng Z, Wei S, Kai S

Abstract
The present study aimed to investigate the significance of hedgehog signaling pathway in association with clinicopathology parameters and its effect on angiogenesis in oral squamous cell carcinoma (OSCC). The expression of Sonic Hh (Shh) and Gli1 were done on primary tumors and metastatic lymph nodes in OSCC samples from 80 patients by immunohistochemical analysis. The western blot was used to examine the expression of Shh in OSCC cell lines and OSCC-derived microvesicles (MVs). The role of Shh carried by MVs to induce endothelial cell angiogenesis was further investigated by matrigel assay. Our results indicated that the expression of Shh was positive associated with microvesseldentisty(MVD), TNM stage, tumor recurrence and lymph node metastasis. Moreover, Shh and Gli1 expression were higher in paired metastatic lymph nodes compared with expression of their primary tumors. The expression of Shh was abundant in Cal27, and present in SCC4, SCC9, and the amount of Shh protein in Cal27 targeting MVs was increased significantly than Cal27 cell group, up to ∼ fifth-fold. The Cal27 derived MVs increased significantly angiogenesis of HUVECs in vitro, and this effect was blocked with exoenzyme C3 transferase (C3) and shRNA targeting RhoA by suppressing RhoA expression and activation. The data suggested that OSCC derived Shh carried by MVs may facilitate the tumor growth and modulate the preparation of a vascular network in primary tumor and/or premetastatic niche.

PMID: 28886265 [PubMed - as supplied by publisher]

http://ift.tt/2xcH35l

Evaluation and management of skeletal disease in cancer care

Publication date: Available online 8 September 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Anuhya Kommalapati, Mary Angelynne Esquivel, Ricardo Correa, Sri Harsha Tella
Recently, there have been considerable advancements in cancer therapies thereby prolonging the life of cancer survivors. However, these recent advancements present new challenges in the management of bone disease in cancer survivors. Bone acts as a fertile soil for cancer seeding and bone health is often compromised because of increased inflammatory cytokines in cancer, direct cancer metastasis and toxic effects of anti-cancer therapies. This effect is more pronounced in elderly population who already have compromised bone mineral density leading to increased skeletal related events and bone pain. Timely diagnosis and effective interventions are essential for reducing bone-related morbidity in cancer survivors. Also, a complex interdependence exists between cancer related bone disease and tumor growth, creating a vicious circle of extensive bone destruction and cancer progression. Hence, maintenance of bone health and integrity plays a pivotal role in comprehensive cancer care. The bone-targeted treatments have been shown to preserve bone health, and modify the course of the underlying cancer. Management of long-term bone health requires a broad knowledge base that both endocrinologists, oncologists and other care team members should be aware of. The manuscript highlights the skeletal effects of cancer, adjuvant therapies used for hormone-responsive cancers, chemotherapy induced bone loss and steps for accurate diagnosis and management of bone disease in cancer survivors by bridging the gaps in the comprehensive cancer care.



http://ift.tt/2wPctPD

Not all immune-checkpoint inhibitors are created equal: Meta-analysis and systematic review of immune-related adverse events in cancer trials

Publication date: Available online 8 September 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): B. El Osta, F. Hu, R. Sadek, R. Chintalapally, S.-C. Tang
BackgroundTargeting immune checkpoints is a novel approach in cancer therapy. This strategy may trigger immune related adverse events (irAE). We hypothesize that the incidence of irAE will be greater in patients receiving immune checkpoint inhibitors (ICI) targeting only immune cells compared to those that also target tumor cells (PD-L1). In addition, we compared the specific irAE profile and overall response rate (ORR) for each ICI by target(s).Materials and methodsWe reviewed all ICI cancer clinical trials (90; 174 arms) that reported irAE and were published through MEDLINE. 114 arms from 73 trials were eligible for this meta-analysis (including 11,328 patients). We collected and compared arm-specific data including ICI target, number of patients with irAE of any grade, grade 3+ and grade 5, specific irAE, and ORR. The R package "meta" was used to conduct a meta-analysis to calculate and compare the percentage of patients with irAE and ORR.ResultsThe incidence (% of patients) of any grade irAE per ICI target was reported for 40 arms (3,418 patients) treated with ICI. Most arms (80%) and patients (53%) studied were on phase 1/2 clinical trials. Patients were treated for solid malignancy on 39 arms (97%), mainly melanoma (40%). Two arms included ICI combinations. The incidence of any grade irAE was higher in patients who received ICI targeting CTLA-4 (53.8%) than PD-1 (26.5%) and PD-L1 ICI (17.1%) (P <0.001). Comparative specific irAE rates were calculated for each ICI target.ConclusionsOur systematic review supported our mechanistic-driven hypothesis. We encourage investigators to report the incidence of irAE in future ICI combination trials.



http://ift.tt/2facbc8

Durable complete remission of poor performance status metastatic lung adenocarcinoma patient treated with second-line erlotinib: a case report

http://ift.tt/2eUOOpM

Biomarker analysis and clinical relevance of TK1 on the cell membrane of Burkitt’s lymphoma and acute lymphoblastic leukemia

http://ift.tt/2eU9pL1

Long-term patient reported outcomes following radiation therapy for oropharyngeal cancer: cross-sectional assessment of a prospective symptom survey in patients ≥65 years old

Given the potential for older patients to experience exaggerated toxicity and symptoms, this study was performed to characterize patient reported outcomes in older patients following definitive radiation thera...

http://ift.tt/2xk06vn