Molecular Data and the IPSS-R: How Mutational Burden Can Affect Prognostication in MDS

Abstract

Purpose of Review

The purpose of this study is to review established prognostic models in myelodysplastic syndromes (MDS) and describe how molecular data can be used to improve patient risk stratification.

Recent Findings

Somatic mutations are common in MDS and are associated with disease features including outcomes. Several recurrently mutated genes have prognostic significance independent of risk stratification tools used in practice. However, this prognostic impact can depend on the clinicogenetic context in which mutations occur. Qualitatively, SF3B1 mutations appear favorable only in patients with < 5% bone marrow blasts while mutations of several genes, including ASXL1, SRSF2, U2AF1, NRAS, and IDH2, appear adverse in this context. Mutations of TP53, RUNX1, and EZH2 appear adverse regardless of blast percentage. Consensus on how to best incorporate mutations into risk assessment is still being developed.

Summary

Somatic mutations can refine risk stratification and improve the accuracy of existing prognostic models, often upstaging or downstaging patients across the boundary of higher- and lower-risk MDS.

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A novel mutation in the COL2A1 gene in a patient with Stickler syndrome type 1: a case report and review of the literature

Stickler syndrome is a group of collagenopathies characterized by ophthalmic, skeletal, and orofacial abnormalities, with the degree of symptoms varying among patients. Mutations in the COL2A1, COL11A1, and COL11...

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Impact of therapy on genomics and transcriptomics in high-risk prostate cancer treated with neoadjuvant docetaxel and androgen deprivation therapy

Background: The combination of docetaxel chemotherapy and androgen deprivation therapy (ADT) has become a standard treatment for patients with metastatic prostate cancer. The recently accrued Phase III CALGB 90203 trial was designed to investigate the clinical effectiveness of this treatment approach earlier in the disease. Specimens from this trial offer a unique opportunity to interrogate the acute molecular response to docetaxel and ADT and identify predictive biomarkers. Methods: We evaluated baseline clinical data, needle biopsies and radical prostatectomy (RP) specimens from 52 (of 788) patients enrolled on CALGB 90203 at one high volume center. Pathology review, tumor and germline targeted DNA sequencing (n=72 genes), and expression profiling using Nanostring platform (n=163 genes) were performed to explore changes in critical prostate cancer pathways linked to aggression and resistance. Results: 3/52 patients had only microfocal residual cancer at prostatectomy. The most common alterations included TMPRSS2-ERG fusion (n=32), TP53 mutation or deletion (n=11), PTEN deletion (n=6), FOXA1 (n=6), SPOP (n=4) mutation, with no significant enrichment in post-treated specimens. We did not observe AR amplification or mutations. The degree of AR signaling suppression varied among treated tumors and there was up-regulation of both AR and AR-V7 expression as well as a subset of neuroendocrine and plasticity genes. Conclusions: These data support the feasibility of targeted and temporal genomic and transcriptome profiling of neoadjuvant-treated prostate cancer with limited formalin-fixed paraffin embedded tissue requirement. Characterization of the heterogeneity of treatment response and molecular outliers that arise post-treatment provides new insight into potential early markers of resistance.

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Microvascular reactivity monitored with near-infrared spectroscopy is impaired after induction of anaesthesia in cardiac surgery patients: An observational study.

BACKGROUND: Induction of anaesthesia causes significant macrohaemodynamic changes, but little is known about its effects on the microcirculation. However, alterations in microvascular perfusion are known to be associated with impaired tissue oxygenation and organ dysfunction. Microvascular reactivity can be assessed with vascular occlusion testing, which evaluates the response of tissue oxygen saturation to transient ischaemia and reperfusion. OBJECTIVE: The aim of the current study was to evaluate the effects of an opioid-based anaesthesia induction on microvascular reactivity. We hypothesised that despite minimal blood pressure changes, microvascular function would be impaired. DESIGN: Prospective, observational study. SETTING: Single-centre, tertiary university teaching hospital, Belgium. PATIENTS: Thirty-five adult patients scheduled for elective coronary artery bypass grafting surgery. INTERVENTION: Microvascular reactivity was assessed before and 30 min after anaesthesia induction by means of vascular occlusion testing and near-infrared spectroscopy. MAIN OUTCOME MEASURES: Tissue oxygen saturations, desaturation rate, recovery time (time from release of cuff to the maximum value) and rate of recovery were determined. RESULTS: Data are expressed as median (minimum to maximum). Tissue oxygen saturation was higher after induction of anaesthesia [70 (54 to 78) vs. 73 (55 to 94)%, P = 0.015]. Oxygen consumption decreased after induction, appreciable by the higher minimum tissue oxygen saturation [45 (29 to 69) vs. 53 (28 to 81)%, P

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Research ethics committee approval as reported for abstracts submitted to the annual Euroanaesthesia meeting.

BACKGROUND: The annual congress of the European Society of Anaesthesiology (ESA) is one of the largest anaesthesia congresses in the world and exhibits more than 1200 abstracts annually. OBJECTIVES: The aims of this study were to quantify the frequency of inadequate evidence of ethical approval for abstracts submitted to the ESA congress and to examine whether abstracts without appropriate ethical approval were subsequently accepted. DESIGN AND SETTING: All abstracts submitted in 2015 were adjudicated according to European ethical criteria. MAIN OUTCOME MEASURE: The proportion of submitted abstracts that lacked evidence of appropriate ethics committee approval. Secondary outcomes included the proportion of accepted abstract that lacked evidence of appropriate ethical approval; the proportion of correctly identified case reports; the proportion of accepted abstracts that lacked evidence of appropriate ethics committee approvals corresponding to location (within/outside Europe); and the proportion of accepted abstracts that lacked evidence of appropriate ethics committee approvals corresponding to a specific area of research. RESULTS: In total, 1792 abstracts were reviewed and 1572 (87.7%) involved humans. In 527 (29.4%), the authors failed to demonstrate adequate ethical approval with higher rates in abstracts submitted from Europe (32.1%) than the rest of the world (23.5%), P

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Calendar

Publication date: September 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 9





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Preoperative biliary drainage in hilar cholangiocarcinoma: Systematic review and meta-analysis

Publication date: September 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 9
Author(s): A. Celotti, L. Solaini, G. Montori, F. Coccolini, D. Tognali, G. Baiocchi
BackgroundThe role of preoperative biliary drainage (PBD) for hilar cholangiocarcinoma (HCC) remains unclear. The aim of this meta-analysis is to investigate the role of PBD in the treatment of potentially resectable HCC.MethodsAll studies reporting outcomes on patients with PBD vs without PBD were included. A systematic literature search was performed in PubMed, Embase, and the Cochrane Library for studies published between 1980 and 2016.ResultsInitial search identified 667 articles. Only 9 studies met the inclusion criteria and were included in this analysis. No significant differences in mortality were observed between the two groups (RR = 0,935; 95% CI = 0,612 to 1429; p = 0,463). Overall morbidity was significantly higher in PBD group (RR = 1266; 95% CI = 1039 to 1543; p = 0,011). No significant differences in transfusion rate, hospital stay, anastomotic leaks, abdominal collections and operative time, were found. Wound infections were significantly higher in PBD group.ConclusionsPBD seems to be associated with higher postoperative morbidity and increases the risk of wound infections. Further prospective studies are needed to better define the impact of PBD in outcomes after surgery for hilar cholangiocarcinoma.



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Editorial Board

Publication date: September 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 9





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Announcements

Publication date: September 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 9





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Heart Attack, Stroke Risk May Be Elevated Following Cancer Diagnosis

A diagnosis of cancer can come with an increased risk of a heart attack or stroke in the months after beginning treatment, a new study suggests. Within 6 months of a diagnosis, the risk of either event was more than twice that seen in people without cancer.

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Docetaxel, Cisplatin, and 5-fluorouracil (DCF) chemotherapy in the treatment of metastatic or unresectable locally recurrent anal squamous cell carcinoma: a phase II study of French interdisciplinary GERCOR and FFCD groups (Epitopes-HPV02 study)

Abstract

Background

The squamous cell carcinoma of the anus (SCCA) is a rare disease, but its incidence is markedly increasing. About 15% of patients are diagnosed at metastatic stage, and more than 20% with a localized disease treated by chemoradiotherapy (CRT) will recur. In advanced SCCA, cisplatin and 5-fluorouracil (CF) combination is the standard option but complete response is a rare event and the prognosis remains poor with most disease progression occurring within the first 12 months.

We have previously published the potential role of the addition of docetaxel (D). Among 8 consecutive patients with advanced recurrent SCCA after CRT, the DCF regimen induced a complete response in 4 patients, including 3 pathological complete responses.

Then, the Epitopes-HPV02 study was designed to confirm the interest of DCF regimen in SCCA patients.

Methods

This multicentre phase II trial assesses the DCF regimen in advanced SCCA patients. Main eligibility criteria are: histologically proven SCCA, unresectable locally advanced recurrent or metastatic disease, Eastern Cooperative Oncology Group-performance status (ECOG-PS) <2, and being eligible for DCF. Patients receive either 6 cycles of standard DCF or 8 cycles of modified DCF depending on age (> vs. ≤ 75 years-old) and ECOG-PS (0 vs. 1). The trial was set up based on a Simon's optimal two-stage design for phase II trials, allowing an early futility interim analysis. The primary endpoint is the observed progression-free survival (PFS) rate at 12 months from the first DCF cycle. A PFS rate below 10% is considered uninteresting, while a PFS rate above 25% is expected. With a unilateral alpha error of 5% and a statistical power of 90%, 66 evaluable patients should be included. Main secondary endpoints are overall survival, PFS, response rate, safety, health-related quality of life, and the correlation of biomarkers with treatment efficacy.

Discussion

Since the recommended CF regimen is based in a small retrospective analysis and generates a low rate of complete responses, the Epitopes-HPV02 study will establish a new standard in case of a positive result. Associated biomarker studies will contribute to understand the underlying mechanism of resistance and the role of immunity in SCCA.

Trial registration

NCT02402842, EudraCT: 2014–001789-81.

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The social and behavioral influences (SBI) study: study design and rationale for studying the effects of race and activation on cancer pain management

Abstract

Background

Racial disparities exist in the care provided to advanced cancer patients. This article describes an investigation designed to advance the science of healthcare disparities by isolating the effects of patient race and patient activation on physician behavior using novel standardized patient (SP) methodology.

Methods/design

The Social and Behavioral Influences (SBI) Study is a National Cancer Institute sponsored trial conducted in Western New York State, Northern/Central Indiana, and lower Michigan. The trial uses an incomplete randomized block design, randomizing physicians to see patients who are either black or white and who are "typical" or "activated" (e.g., ask questions, express opinions, ask for clarification, etc.). The study will enroll 91 physicians.

Discussion

The SBI study addresses important gaps in our knowledge about racial disparities and methods to reduce them in patients with advanced cancer by using standardized patient methodology. This study is innovative in aims, design, and methodology and will point the way to interventions that can reduce racial disparities and discrimination and draw links between implicit attitudes and physician behaviors.

Trial registration

http://ift.tt/1pydFNc, #NCT01501006, November 30, 2011.

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Surveillance active du cancer de la prostate

Publication date: Available online 25 August 2017
Source:Cancer/Radiothérapie
Author(s): G. Ploussard, C. Hennequin, F. Rozet
Plusieurs essais prospectifs ont maintenant validé la surveillance active dans la prise en charge du cancer de la prostate localisé, ce qui permet d'éviter un traitement inutile à beaucoup de patients. Elle s'adresse essentiellement au groupe pronostique à bas risque, comme le préconise par l'American Society of Clinical Oncology (ASCO). Elle pourrait également intéresser les patients du groupe intermédiaire, mais cela reste discuté. Actuellement, la présence d'adénocarcinome de grade 4 est une contre-indication relative à la surveillance active. Ses modalités intègrent un dosage itératif de l'antigène spécifique de la prostate et une nouvelle biopsie systématique dans l'année suivant le diagnostic. La place de l'IRM, à la fois lors de l'inclusion du patient et de la surveillance, a été récemment introduite dans plusieurs recommandations internationales. Enfin, aucune approche comportementale ou médicamenteuse visant à allonger la durée de surveillance n'a, pour l'instant, pas été validée.Several prospective studies have demonstrated the safety of active surveillance as a first treatment of prostate cancer. It spares many patients of a useless treatment, with its potential sequelae. Patients with a low-risk cancer are all candidates for this approach, as recommended by the American Society of Clinical Oncology (ASCO). Some patients with an intermediate risk could be also concerned by active surveillance, but this is still being discussed. Currently, the presence of grade 4 lesions on biopsy is a contra-indication. Modalities included a repeated prostate specific antigen test and systematic rebiopsy during the first year after diagnosis. MRI is now proposed to better select patients at inclusion and also during surveillance. No life style changes or drugs are significantly associated with a longer duration of surveillance.



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Radiothérapie stéréotaxique hépatique : organes à risque, marges d’incertitudes, doses

Publication date: Available online 24 August 2017
Source:Cancer/Radiothérapie
Author(s): T. Lacornerie, E. Rio, M.-A. Mahé
La radiothérapie en conditions stéréotaxiques des tumeurs hépatiques primitives et secondaires peut être réalisée en complément et/ou comme une alternative à la chirurgie et aux techniques de thermoablation. De nombreuses variantes techniques sont actuellement disponibles, ce qui entraîne une certaine hétérogénéité dans les modalités de délinéation, de prescription de la dose et de détermination des doses de tolérance aux organes à risque. L'objectif de cet article est de permettre une homogénéisation des pratiques afin d'améliorer la qualité et la sécurité de cette technique et de faciliter sa diffusion afin de répondre au principe d'égalité d'accès aux techniques innovantes pour le plus grand nombre de patients. Cette mise au point s'inscrit dans la continuité du guide Recorad, publié en 2016 par la Société française de radiothérapie oncologique (SFRO), en le complétant selon les données récentes de la littérature sur les tumeurs du foie.Stereotactic body radiation therapy for primary and metastatic hepatic malignancies can be performed in association and/or as an alternative to surgery and radiofrequency. The consequences of the great number of techniques available are heterogeneity in contouring, dose prescription and in determination of dose constraints for organs at risk. The objective of this paper is to improve the quality and safety and to help the diffusion of this technique for a majority of patients. In 2016, the French Society of Radiation Oncology (SFRO) published guidelines for external radiotherapy and brachytherapy ("Recorad"). This paper is an update of these recommendations considering recent publications.



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Tumour-derived plasma cell-free DNA in patients with head and neck cancer: A short review

Publication date: Available online 25 August 2017
Source:Cancer/Radiothérapie
Author(s): M. Rave-Fränk
Head and neck squamous cell carcinoma is one of the leading causes of cancer mortality worldwide. The prognosis for patients with head and neck squamous cell carcinoma has not substantially improved during the last decades, despite numerous advancements in treatment options. Reliable markers for early tumour detection and treatment response, which complement clinical examinations, imaging techniques, and biopsies would be extremely useful. One fairly new and promising method is the analysis of tumour-derived cell-free DNA (ctDNA) in the plasma of cancer patients. First data indicate that this method may assist, in the future, in the early detection of head and neck squamous cell carcinoma, the real-time monitoring of the disease course, the therapy response, and the prediction of prognosis with direct therapeutic implications by determining the best therapeutic modality for patient care.



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Outcome of colon cancer initially presenting as colon perforation and obstruction

Abstract

Background

Emergency complications of colon cancer include perforation and obstruction which were recognized as poor prognostic factors. Few studies have directly compared the outcomes of these two groups. In this study, we evaluated mortality and morbidity in patients with colon cancer initially presenting as perforation and obstruction.

Methods

Newly diagnosed colon cancer cases initially presenting with perforation or obstruction at Tzu Chi General Hospital, Hualien, Taiwan, between 2009 and 2015 were included. Cases of iatrogenic perforation or perforation sites far away from the tumor sites and rectal (< 15 cm from the anal verge) cancer were excluded. Progression-free survival, local recurrence rate, distant metastasis rate, and overall survival were the evaluated outcomes.

Results

Eighty-one patients met the selection criteria; 23 and 58 patients had perforation and obstruction, respectively, as the initial symptom. The median age was 72 years. The median tumor stage was stage IIIB. The 1-year and 3-year survival rates were 83.7 and 59.7%, respectively. The perforation group (PRG) and obstruction group (OBG) did not differ significantly in intensive care unit (ICU) stay rate (p = 0.147), sex (p = 0.45), comorbidities (heart, liver, and renal diseases and diabetes mellitus), median stage (p = 0.198), and overall survival (p = 0.328). However, PRG had a higher age at diagnosis (74 vs. 64 years, p = 0.037), a higher APACHE II score (12 vs. 7, p = 0.002), lower disease-free survival (p = 0.001), a higher recurrence rate (56.5 vs. 19%, p = 0.002), a higher distant metastasis rate (39.1 vs. 13.8%, p = 0.015), and a higher local recurrence rate (43.5 vs. 5.2%, p < 0.001) than did OBG. OBG had a higher two-stage operation rate (46.6 vs. 17.4%, p = 0.022). After adjustment for the tumor stage, comorbidity (chronic renal disease), body mass index (BMI), and adjuvant chemotherapy or radiotherapy in multivariate statistics, PRG had lower disease-free survival (p = 0.005) than OBG but overall survival was identical.

Conclusion

For colon cancer initially presenting as perforation or obstruction, the PRG had poorer progression-free survival, a higher local recurrence rate, and a higher distant metastasis rate than did OBG. Overall survival did not differ between these two groups.

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Heavy alcohol drinking downregulates ALDH2 gene expression but heavy smoking up-regulates SOD2 gene expression in head and neck squamous cell carcinoma

Abstract

Background

This study aims to determine the relationship between expression levels of ALDH2 and SOD2 genes and clinical parameters such as alcohol drinking, tobacco smoking, primary site of HNSCC, and human papilloma virus (HPV) state.

Methods

Gene expression data were obtained from gene expression omnibus (GEO accession number: GSE65858). Clinical data (N = 270) including survival result, gender, age, TNM stage, primary site of HNSCC, HPV status, alcohol drinking, and tobacco smoking habit were analyzed according to gene expression pattern.

Results

ALDH2 gene was expressed in low levels in patients with heavy alcohol consumption. It was expressed in high (p = 0.01) levels in patients with no or light alcohol consumption. ALDH2 gene was also expressed in low levels in patients with oral cavity cancers or hypopharynx cancers. However, ALDH2 gene was expressed in high (p = 0.03) levels in patients with oropharyngeal cancers or laryngeal cancers. HPV-positive patients were found to have high (p = 0.02) expression levels of ALDH2. SOD2 gene was expressed in high (p = 0.005) levels in patients who had greater mean pack-year of tobacco smoking. Based on log rank test, the group of patients with high expression of ALDH2 showed better (p = 0.002) clinical results than those with low expression of ALDH2. Difference of survival results between ALDH2 high-expressed group and ALDH2 low-expressed group was validated in another cohort (GSE39368, N = 138).

Conclusions

Heavy alcohol drinking downregulates ALDH2 gene expression level. Heavy smoking up-regulates SOD2 gene expression level in patients with head and neck squamous cell carcinoma. The group of patients with low expression levels of ALDH2 showed significantly poorer survival results compared to those with high expression levels of ALDH2.

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Hypoxic exosomes facilitate bladder tumor growth and development through transferring long non-coding RNA-UCA1

Abstract

Background

To overcome the hostile hypoxic microenvironment of solid tumors, tumor cells secrete a large number of non-coding RNA-containing exosomes that facilitate tumor development and metastasis. However, the precise mechanisms of tumor cell-derived exosomes during hypoxia are unknown. Here, we aim to clarify whether hypoxia affects tumor growth and progression by transferring long non-coding RNA-urothelial cancer-associated 1 (lncRNA-UCA1) enriched exosomes secreted from bladder cancer cells.

Methods

We used bladder cancer 5637 cells with high expression of lncRNA-UCA1 as exosome-generating cells and bladder cancer UMUC2 cells with low expression of lncRNA-UCA1 as recipient cells. Exosomes derived from 5637 cells cultured under normoxic or hypoxic conditions were isolated and identified by transmission electron microscopy, nanoparticle tracking analysis and western blotting analysis. These exosomes were co-cultured with UMUC2 cells to evaluate cell proliferation, migration and invasion. We further investigated the roles of exosomal lncRNA-UCA1 derived from hypoxic 5637 cells by xenograft models. The availability of lncRNA-UCA1 in serum-derived exosomes as a biomarker for bladder cancer was also assessed.

Results

We found that hypoxic exosomes derived from 5637 cells promoted cell proliferation, migration and invasion, and hypoxic exosomal RNAs could be internalized by three bladder cancer cell lines. Importantly, lncRNA-UCA1 was secreted in hypoxic 5637 cell-derived exosomes. Compared with normoxic exosomes, hypoxic exosomes derived from 5637 cells showed the higher expression levels of lncRNA-UCA1. Moreover, Hypoxic exosomal lncRNA-UCA1 could promote tumor growth and progression though epithelial-mesenchymal transition, in vitro and in vivo. In addition, the expression levels of lncRNA-UCA1 in the human serum-derived exosomes of bladder cancer patients were higher than that in the healthy controls.

Conclusion

Together, our results demonstrate that hypoxic bladder cancer cells remodel tumor microenvironment to facilitate tumor growth and development though secreting the oncogenic lncRNA-UCA1-enriched exosomes and exosomal lncRNA-UCA1 in human serum has the possibility as a diagnostic biomarker for bladder cancer.

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Effect of time to initiation of postoperative radiation therapy on survival in surgically managed head and neck cancer

BACKGROUND

The objective of this study was to determine the effects of National Comprehensive Cancer Network (NCCN) guideline–adherent initiation of postoperative radiation therapy (PORT) and different time-to-PORT intervals on the overall survival (OS) of patients with head and neck squamous cell carcinoma (HNSCC).

METHODS

The National Cancer Data Base was reviewed for the period of 2006-2014, and patients with HNSCC undergoing surgery and PORT were identified. Kaplan-Meier survival estimates, Cox regression analysis, and propensity score matching were used to determine the effects of initiating PORT within 6 weeks of surgery and different time-to-PORT intervals on survival.

RESULTS

This study included 41,291 patients. After adjustments for covariates, starting PORT >6 weeks postoperatively was associated with decreased OS (adjusted hazard ratio [aHR], 1.13; 99% confidence interval [CI], 1.08-1.19). This finding remained in the propensity score–matched subset (hazard ratio, 1.21; 99% CI, 1.15-1.28). In comparison with starting PORT 5 to 6 weeks postoperatively, initiating PORT earlier was not associated with improved survival (aHR for ≤ 4 weeks, 0.93; 99% CI, 0.85-1.02; aHR for 4-5 weeks, 0.92; 99% CI, 0.84-1.01). Increasing durations of delay beyond 7 weeks were associated with small, progressive survival decrements (aHR, 1.09, 1.10, and 1.12 for 7-8, 8-10, and >10 weeks, respectively).

CONCLUSIONS

Nonadherence to NCCN guidelines for initiating PORT within 6 weeks of surgery was associated with decreased survival. There was no survival benefit to initiating PORT earlier within the recommended 6-week timeframe. Increasing durations of delay beyond 7 weeks were associated with small, progressive survival decrements. Cancer 2017. © 2017 American Cancer Society.

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A Darwinian view of cancer and the environment

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Phase 1 dose escalation multicenter trial of pracinostat alone and in combination with azacitidine in patients with advanced hematologic malignancies

BACKGROUND

Pracinostat is a potent histone deacetylase inhibitor with antitumor activity in both solid tumor and acute myeloid leukemia (AML) cell lines. Pracinostat is reported to have modest clinical activity in patients with advanced solid tumors. Given the higher preclinical sensitivity of hematologic malignancies to pracinostat, the authors conducted a phase 1 study to assess the safety, maximum tolerated dose, recommended phase 2 dose, efficacy, pharmacokinetics, and pharmacodynamics of pracinostat in patients with advanced hematological malignancies.

METHODS

Pracinostat was administered orally 3 times a week for 3 weeks on a 28-day cycle. Patients were assigned to 7 dose levels using a 3 + 3 dose escalation design.

RESULTS

A total of 44 patients were enrolled, 25 of whom had AML and 14 of whom had myelodysplastic syndrome. The maximum tolerated dose was 120 mg and the recommended phase 2 dose was 60 mg. Two patients with AML achieved a response: 1 complete remission (CR) and 1 complete cytogenetic response. Despite a dose-dependent increase in the plasma concentration of pracinostat, a similar increase in histone acetylation was not observed. As an extension, 10 additional patients with myelodysplastic syndrome were enrolled to assess the safety and efficacy of pracinostat in combination with azacitidine. Six patients achieved a CR and 3 achieved a CR without platelet recovery with no added toxicity.

CONCLUSIONS

The results of the current study demonstrate that pracinostat is safe, with modest single-agent activity in patients with hematological malignancies. Cancer 2017. © 2017 American Cancer Society.

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Long-term weight loss after colorectal cancer diagnosis is associated with lower survival: The Colon Cancer Family Registry

BACKGROUND

Body weight is associated with colorectal cancer (CRC) risk and survival, but to the authors' knowledge, the impact of long-term postdiagnostic weight change is unclear. Herein, the authors investigated whether weight change over the 5 years after a diagnosis of CRC is associated with survival.

METHODS

CRC cases diagnosed from 1997 to 2008 were identified through 4 population-based cancer registry sites. Participants enrolled within 2 years of diagnosis and reported their height and weight 2 years prior. Follow-up questionnaires were administered approximately 5 years after diagnosis. Associations between change in weight (in kg) or body mass index (BMI) with overall and CRC-specific survival were estimated using Cox regression analysis adjusted for age, sex, American Joint Committee on Cancer stage of disease, baseline BMI, nonsteroidal anti-inflammatory drug use, smoking, time between diagnosis and enrollment, and study site.

RESULTS

At the 5-year postdiagnostic survey, 2049 participants reported higher (53%; median plus 5 kg), unchanged (12%), or lower (35%; median -4 kg) weight. Over a median of 5.1 years of subsequent follow-up (range, 0.3-9.9 years), 344 participants died (91 of CRC). Long-term weight loss (per 5 kg) was found to be associated with poorer overall survival (hazard ratio, 1.13; 95% confidence interval, 1.07-1.21) and CRC-specific survival (hazard ratio, 1.25; 95% confidence interval, 1.13-1.39). Significantly lower survival was similarly observed for relative weight loss (>5% vs ≤5% change), BMI reduction (per 1 unit), or BMI category change (overweight to normal vs remaining overweight).

CONCLUSIONS

Weight loss 5 years after a diagnosis of CRC was found to be significantly associated with decreased long-term survival, suggesting the importance of avoiding weight loss in survivors of CRC. Future research should attempt to further evaluate this association, accounting for whether this weight change was intentional or represents a marker of declining health. Cancer 2017. © 2017 American Cancer Society.

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Inhibiting heat shock protein 90 and the ubiquitin-proteasome pathway impairs metabolic homeostasis and leads to cell death in human pancreatic cancer cells

BACKGROUND

Heat shock protein 90 (HSP90) and the ubiquitin-proteasome pathway play crucial roles in the homeostasis of pancreatic cancer cells. This study combined for the first time the HSP90 inhibitor ganetespib (Gan) and the proteasome inhibitor carfilzomib (Carf) to target key mechanisms of homeostasis in pancreatic cancer. It was hypothesized that Gan plus Carf would elicit potent antitumor activity by modulating complementary homeostatic processes.

METHODS

In vitro and in vivo effects of this combination on mechanisms of cell growth and viability were evaluated with human pancreatic cancer cell lines (MIA PaCa-2 and HPAC).

RESULTS

Combined treatment with Gan and Carf significantly decreased cell viability. The mechanism varied by cell line and involved G₂-M cell-cycle arrest accompanied by a consistent reduction in key cell-cycle regulatory proteins and concomitant upregulation of p27. Further studies revealed increased autophagy markers, including the upregulation of autophagy related 7 and light chain 3 cleavage, and evidence of apoptosis (increased Bax expression and processing of caspase 3). Immunoblot analyses confirmed the modulation of other pathways that influence cell viability, including phosphoinositide 3-kinase/Akt and nuclear factor κB. Finally, the treatment of athymic mice bearing HPAC tumors with Gan and Carf significantly reduced tumor growth in vivo. An immunoblot analysis of freshly isolated tumors from animals at the end of the study confirmed in vivo modulation of key signaling pathways.

CONCLUSIONS

The results reveal Gan plus Carf to be a promising combination with synergistic antiproliferative, apoptotic, and pro-autophagy effects in preclinical studies of pancreatic cancer and will further the exploration of the utility of this treatment combination in clinical trials. Cancer 2017. © 2017 American Cancer Society.

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The role of surgery and adjuvant therapy in lymph node-positive cancers of the gallbladder and intrahepatic bile ducts

BACKGROUND

Lymph node metastasis is a poor prognostic factor for biliary tract cancers (BTCs). The optimal management of patients who have BTC with positive regional lymph nodes, including the impact of surgery and adjuvant therapy (AT), is unclear.

METHODS

This was a retrospective cohort study of patients who had T1-T3N1M0 gallbladder cancer (GBC) and intrahepatic cholangiocarcinoma (IHC) in the National Cancer Database (2004-2012). Patients were classified by treatment approach (nonoperative, surgery, surgery plus AT). Associations between the overall risk of death and treatment strategy were evaluated with multivariable Cox regression.

RESULTS

Rates of surgical resection were 84.1% for patients with GBC (n = 1335) and 36.6% for those with IHC (n = 1009). The median overall survival of patients in the nonoperative, surgery, and surgery plus AT group was 11.6, 13.3, and 19.6 months, respectively, for those with GBC (log-rank P < .001), and 12.7, 16.2, and 22.6 months, respectively, for those with IHC (log-rank P < .001), respectively. Compared with nonoperative therapy, surgery with or without AT was associated with a lower risk of death from GBC (surgery with AT: hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.48-0.73; surgery without AT: HR, 0.71; 95% CI, 0.56-0.89) and from IHC (surgery with AT: HR, 0.52; 95% CI, 0.42-0.63; surgery without AT: HR, 0.70; 95% CI, 0.56-0.87). AT that included radiation was associated with a lower risk of death relative to surgery alone for patients with GBC regardless of margin status (margin-negative resection: HR, 0.66; 95% CI, 0.52-0.84; margin-positive resection: HR, 0.54; 95% CI, 0.39-0.75), but adjuvant chemotherapy alone was not. For patients with IHC, no survival benefit was detected with adjuvant chemotherapy or radiation for those who underwent either margin-positive or margin-negative resection.

CONCLUSIONS

The best outcomes for patients who have lymph node-positive BTCs are associated with margin-negative resection and, in those who have GBC, the inclusion of adjuvant chemotherapy with radiation regardless of margin status. Cancer 2017. © 2017 American Cancer Society.

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Childhood cancer incidence by ethnic group in England, 2001–2007: a descriptive epidemiological study

Abstract

Background

After the first year of life, cancers are the commonest cause of death in children. Incidence rates vary between ethnic groups, and recent advances in data linkage allow for a more accurate estimation of these variations. Identifying such differences may help identify potential risk or protective factors for certain childhood cancers. This study thus aims to ascertain whether such differences do indeed exist using nationwide data across seven years, as have previously been described in adult cancers.

Methods

We obtained data for all cancer registrations for children (aged 0–14) in England from January 2001 to December 2007. Ethnicity (self-assigned) was established through record linkage to the Hospital Episodes Statistics database or cancer registry data. Cancers were classified morphologically according to the International Classification of Childhood Cancer into four groups – leukaemias; lymphomas; central nervous system; and other solid tumours. Age standardised incidence rates were estimated for each ethnic group, as well as incidence rate ratios comparing each individual ethnic group (Indian, Pakistani, Bangladeshi, Black African, Black Carribean, Chinese) to Whites, adjusting for sex, age and deprivation.

Results

The majority of children in the study are UK born. Black children (RR = 1.18, 99% CI: 1.01–1.39), and amongst South Asians, Pakistani children (RR = 1.19, 99% CI: 1.02–1.39) appear to have an increased risk of all cancers. There is an increased risk of leukaemia in South Asians (RR = 1.31, 99% CI: 1.08–1.58), and of lymphoma in Black (RR = 1.72, 99% CI: 1.13–2.63) and South Asian children (RR = 1.51, 99% CI: 1.10–2.06). South Asians appear to have a decreased risk of CNS cancers (RR = 0.71, 99% CI: 0.54–0.95).

Conclusions

In the tradition of past migrant studies, such descriptive studies within ethnic minority groups permit a better understanding of disease incidence within the population, but also allow for the generation of hypotheses to begin to understand why such differences might exist. Though a major cause of mortality in this age group, childhood cancer remains a relatively rare disease; however, the methods used here have permitted the first nationwide estimation of childhood cancer by individual ethnic group.

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Urokinase-type plasminogen activator receptor (uPAR), tissue factor (TF) and epidermal growth factor receptor (EGFR): tumor expression patterns and prognostic value in oral cancer

Abstract

Background

Tumor-specific biomarkers are a prerequisite for the development of targeted imaging and therapy in oral squamous cell carcinoma (OSCC). urokinase-type Plasminogen Activator Receptor (uPAR), Tissue Factor (TF) and Epidermal Growth Factor Receptor (EGFR) are three biomarkers that exhibit enhanced expression in many types of cancers, and have been investigated as potential biomarkers for targeted strategies and prognostication. The aim of the study was to investigate the expression patterns of uPAR, TF and EGFR and their potential prognostic value in OSCC.

Methods

Immunohistochemical expression of uPAR, TF and EGFR in tumor resection specimens from 191 patients with primary OSCC was analyzed. Overall (OS) and disease-free survival (DFS) was calculated. Associations between biomarker expression, clinicopathological factors and patient survival was analyzed using the Cox proportional hazards model for univariate and multivariate analysis, log rank and Kaplan-Meier statistics.

Results

uPAR and TF exhibited a highly tumor-specific expression pattern while EGFR also showed expression in normal tissues outside the tumor compartment. The overall positive expression rate of uPAR, TF and EGFR was 95%, 58% and 98%, respectively. High uPAR expression across the entire cohort was negatively associated with OS (p = 0.031, HR = 1.595 (95%CI 1.044–2.439)) in univariate analysis. The 5-year OS for high and low uPAR expression was 39% and 56%, respectively. The expression of TF and EGFR was not associated with survival outcome.

Conclusions

This study may suggest that uPAR and TF could potentially be attractive targets for molecular imaging and therapy in OSCC due to high positive expression rates and tumor-specific expression patterns. High uPAR expression was significantly associated with a reduced survival. uPAR seems to be a prognostic biomarker in oral cancer.

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Skeletal muscle depletion during chemotherapy has a large impact on physical function in elderly Japanese patients with advanced non–small-cell lung cancer

Abstract

Background

Elderly patient with advanced cancer is one of the most vulnerable populations. Skeletal muscle depletion during chemotherapy may have substantial impact on their physical function. However, there is little information about a direct relationship between quantity of muscle and physical function. We sought to explore the quantitative association between skeletal muscle depletion, and muscle strength and walking capacity in elderly patients with advanced non–small cell lung cancer (NSCLC).

Methods

Thirty patients aged ≥70 years with advanced NSCLC (stage III-IV) scheduled to initiate first-line chemotherapy were prospectively enrolled between January 2013 and November 2014. Lumbar skeletal muscle index (LSMI, cm²/m²), incremental shuttle walking distance (ISWD, m), and hand-grip strength (HGS, kg) were assessed at baseline, and 6 ± 2 weeks (T2) and 12 ± 4 weeks (T3) after study enrollment. Associations were analyzed using linear regression.

Results

Altogether, 11 women and 19 men with a median age of 74 (range, 70–82) years were included in the study; 24 received cytotoxic chemotherapy and 6, gefitinib. Mean ± standard deviation of LSMI, ISWD and HGS were 41.2 ± 7.8 cm²/m², 326.0 ± 127.9 m, and 29.3 ± 8.5 kg, respectively. LSMI and ISWD significantly declined from baseline to T2 and T3. HGS significantly declined from baseline to T2 and T3 only in men. Change in LSMI was significantly associated with change in HGS (β = 0.3 ± 0.1, p = 0.0127) and ISWD (β = 8.8 ± 2.4, p = 0.0005).

Conclusions

Skeletal muscle depletion accompanied with physical functional decline started in the early phase of the chemotherapy in elderly patients with advanced NSCLC. Our results suggest that there may be a need for early supportive care in these patients to prevent functional decline during chemotherapy.

Trial registration

Trial registration number: UMIN000009768

Name of registry: UMIN (University hospital Medical Information Network).

URL of registry: Date of registration: 14 January 2013.

Date of enrolment of the first participant to the trial: 23 January 2013.

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Comparison of PSA value at last follow-up of patients who underwent low-dose rate brachytherapy and intensity-modulated radiation therapy for prostate cancer

Abstract

Background

To compare the PSA value at the last follow-up of patients who underwent prostate low-dose rate brachytherapy (LDR-BT) with that of patients who underwent intensity-modulated radiation therapy (IMRT).

Methods

A total of 610 prostate cancer patients (cT1c-3bN0M0) were enrolled, and 445 of them underwent LDR-BT, while 165 received IMRT (74–76 Gy). The median follow-up period of these two groups was 75 months (LDR-BT) and 78 months (IMRT), respectively. We also evaluated the biochemical recurrence (BCR)-free rate using two definitions (Phoenix definition and PSA ≥ 0.2 ng/mL).

Results

The percentage of patients who achieved PSA < 0.2 ng/mL at the last follow-up was 77.5% in the LDR-BT group and 49.7% in the IMRT group (p < 0.001). Among patients with a normal testosterone level at the last follow-up, the percentage of those who achieved PSA < 0.2 ng/mL at the last follow-up was 79.2% in the LDR-BT group and 32.1% in the IMRT group (p < 0.001). The 5-year BCR-free rate by the Phoenix definition in the IMRT and LDR-BT groups was 89.5 and 95.0% (p < 0.001), respectively. On the other hand, the 5-year BCR-free rate using the definition of PSA ≥ 0.2 ng/mL was 59.1 and 80.1% in the IMRT and LDR-BT groups, respectively (p < 0.001).

Conclusions

The PSA value at the last follow-up of LDR-BT was significantly lower than that of IMRT, and this result was particularly marked in patients with a normal testosterone level at the last follow-up.

http://ift.tt/2wN8nqU

Utilization of cytocentrifugation slides in flow cytometry laboratory: a tool for correlation of morphology and immunonophenotype

Abstract

Cytocentrifuge slide ("cytospin") is a simple and rapid technique that is mainly used in the cytology laboratory. We have routinely used the technique in flow cytometry (FCM) laboratory at Montefiore Medical Center for more than 15 years. Our aim is to illustrate the contribution of cytospin in direct cellular morphologic visualization in FCM immunophenotyping, in result interpretation, and additionally as a quality control tool. Four thousand two hundred forty-eight cases sent to our FCM Laboratory in the past 21 months were studied retrospectively. The clinical history, cytospins, immunophenotyping panels, FCM contour plots, final FCM reports, and pathology reports were reviewed. Morphologic examination of the cytospin is a cost-effective tool for sample quality screening. Of the 4248 immunophenotyping cases, 359 (8.4%) cases were canceled, according to laboratory protocol based on cytospin review. Morphologic analysis of the cytospin provides extra information that guides both selection of the FCM immunophenotype panel and gating the cells of interest. Additionally, morphologic analysis of cytospin can yield early diagnosis when cohesive benign or malignant non-hematologic cells are present or even infectious organisms such as parasites are identified. Finally, the cytospin is a convenient tool for morphology-phenotype correlation. Cytospin is cost-effective and provides important morphologic information that facilitates FCM immunophenotyping panel selection and result interpretation.

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Use of an endotracheal tube for surgical abortion complicated by a leiomyomatous uterus: a case report

Abnormal uterine anatomy, especially leiomyomas, can significantly impact the difficulty and potential morbidity of surgical uterine evacuation. To avoid hysterotomy and/or hysterectomy, limited evidence exist...

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Anesthetic management during adenotonsillectomy for twins with congenital insensitivity to pain with anhidrosis: two case reports

Congenital insensitivity to pain with anhidrosis is a rare autosomal recessive disorder characterized by hyperpyrexia, anhidrosis, pain insensitivity, self-inflicted injuries, and intellectual disability. The ...

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Mechanisms and risk factors of thrombosis in cancer

Publication date: Available online 25 August 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Anna Falanga, Laura Russo, Viola Milesi, Alfonso Vignoli
The close relationship between cancer and thrombosis is known since more than a century. Venous thromboembolism (VTE) may be the first manifestation of an occult malignancy in an otherwise healthy individual. Cancer patients commonly present with abnormalities of laboratory coagulation tests, indicating an ongoing subclinical hypercoagulable condition. The results of laboratory tests demonstrate that a process of fibrin formation and removal parallels the development of malignancy, which is of particular interest since fibrin and other clotting products are important for both thrombogenesis and tumor progression. Besides general clinical risk factors (i.e. age, previous VTE, immobility, etc), other factors typical of cancer can increase the thrombotic risk in these patients, including the type of cancer, advanced disease stage, and cancer therapies. In addition, biological factors, including tumor cell-specific prothrombotic properties and the host cell inflammatory response to the tumor, play a central role in the pathogenesis of cancer-associated thrombosis. Cancer cells produce and release procoagulant and fibrinolytic proteins, as well as inflammatory cytokines. In addition, they are capable of directly adhering to host cells (i.e. endothelial cells, monocytes, platelets, and neutrophils), thereby stimulating additional prothrombotic properties of the host effector cells. Tumor-shed procoagulant microparticles also contribute to the patient hypercoagulable state. Finally, the changes of stromal cells of the tumor 'niche' induced by tissue factor (TF) highlight new interactions between hemostasis and cancer. Of interest, most of these mechanisms, besides activating the hemostatic system, also promote tumor growth and metastasis, and are regulated by oncogenic events. Indeed, molecular studies demonstrate that oncogenes responsible for the cellular neoplastic transformation drive the programs of hemostatic protein expression and microparticle liberation by cancer tissues. Human and animal experimental models demonstrate that activation of cancer-associated prothrombotic mechanisms parallels the development of overt thrombotic syndromes in vivo.



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Cancer-related Fatigue in Adolescents and Young Adults: A Systematic Review of the Literature

Publication date: Available online 24 August 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): E. Nowe, Y. Stöbel-Richter, A. Sender, K. Leuteritz, M. Friedrich, K. Geue
Adolescents and young adults with cancer (AYA) represent a specific age cohort dealing with the disease in a stage of life characterized by development, upheavals, and establishment. The aim of this study was to point out the state of research on how AYA are affected by cancer-related fatigue (CRF).ResultsTwelve articles were included. CRF was found to be higher in AYA than in either of the comparison groups, healthy peers and older cancer patients. Most included studies did not measure CRF with multidimensional, fatigue-specific instruments.ConclusionWe found a gap in research concerning CRF in AYA. The existing findings suggest that CRF is a significant issue for AYA cancer patients. However, less is known about the prevalence, severity, and impact of CRF in AYA, and their treatment. This should be considered in future research, and risk and prevention factors should be ascertained. Multidimensional and fatigue-specific measuring tools should be used to do this.



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Viruses in cancers among the immunosuppressed

Abstract

Most cancer forms known to be caused by viruses are increased among the immunosuppressed, but several cancer forms without established viral etiology are also increased, notably non-melanoma skin carcinoma (NMSC). We followed all 13429 solid organ transplantation patients in Sweden for cancer occurrence after transplantation. We requested these tumor specimens and sequenced the first 89 specimens received (62 NMSCs, 27 other cancers). The sequences were analyzed for viruses based on two bioinformatics algorithms (paracel-blast (sensitive for detection of known viruses) and hidden Markov model (HMM; sensitive for distantly related viruses)). Among the 62 NMSCs, the virus family detected in the largest proportion of specimens was Mimiviridae (9/62 NMSCs). The majority of the virus-related reads belonged to Papillomaviridae. The HMM analysis identified 86 additional previously not described viral contigs related to 11 virus families, with reads related to Mimiviridae being the most common (detected in 28/62 NMSCs) with the most prevalent contig (Mimivirus SE906, 1937 bp) detected in 17/62 NMSCs. Among the 27 other cancers, viral sequences were detected in only 5 specimens by blast analysis, compared to in all 27 specimens by HMM (Mimiviridae, Poxviridae, Phycodnaviridae and virus-related sequences yet unclassified to any family). 99% of the virus reads belonged to a single previously not described sequence (Mimivirus SE996, 911 bp). A multitude of viruses is readily detectable in specimens with cancers occurring among the immunosuppressed, with sequences related to Mimiviridae being the most prevalent. Further research would be needed to elucidate the biological significance of the viruses. This article is protected by copyright. All rights reserved.

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Nephronectin is Decreased in Metastatic Breast Carcinoma and Related to Metastatic Organs

Abstract

Breast cancer causes death mostly due to distant metastasis. During metastasis, cancer cells create new conditions in which normal tissue structure can be disturbed. Nephronectin, which is the primary ligand for α8β1 integrin, plays an important role in kidney development. There are conflicting findings regarding its role in cancer progression and metastasis, especially in breast carcinoma. The aim of this study was to determine changes in nephronectin expression in primary tumor tissues and metastatic visceral organs, using metastatic and non-metastatic cell lines in a mouse model of breast cancer. In our study, 4T1-Liver Metastatic and 4T1-Heart Metastatic cells, originally derived from 4T1-murine breast carcinoma, and non-metastatic 67NR carcinoma cells were used. Cancer cells were injected orthotopically into the mammary gland of 8–10 week-old Balb-c mice. Primary tumors, lung, liver tissues were collected on 12th and 25th days after the tumor injection. Immunohistochemistry was used to determine expression of nephronectin in tissues. We also investigated the expression levels of the protein by using western blot technique. We found that lung and liver tissue of control animals (not-injected with tumor cells) expressed nephronectin which was lost in animals bearing metastatic tumor for 25 days. In accordance, nephronectin staining of lung and liver was preserved in animals injected with non-metastatic 67NR tumors. These results demonstrate that loss of nephronectin may play an important role in formation metastatic milieu for cancer cells. This is the first study demonstrating that tumor-induced loss of nephronectin expression in visceral organs in which metastatic growth takes place.

http://ift.tt/2wtZNNX

Nephronectin is Decreased in Metastatic Breast Carcinoma and Related to Metastatic Organs

Abstract

Breast cancer causes death mostly due to distant metastasis. During metastasis, cancer cells create new conditions in which normal tissue structure can be disturbed. Nephronectin, which is the primary ligand for α8β1 integrin, plays an important role in kidney development. There are conflicting findings regarding its role in cancer progression and metastasis, especially in breast carcinoma. The aim of this study was to determine changes in nephronectin expression in primary tumor tissues and metastatic visceral organs, using metastatic and non-metastatic cell lines in a mouse model of breast cancer. In our study, 4T1-Liver Metastatic and 4T1-Heart Metastatic cells, originally derived from 4T1-murine breast carcinoma, and non-metastatic 67NR carcinoma cells were used. Cancer cells were injected orthotopically into the mammary gland of 8–10 week-old Balb-c mice. Primary tumors, lung, liver tissues were collected on 12th and 25th days after the tumor injection. Immunohistochemistry was used to determine expression of nephronectin in tissues. We also investigated the expression levels of the protein by using western blot technique. We found that lung and liver tissue of control animals (not-injected with tumor cells) expressed nephronectin which was lost in animals bearing metastatic tumor for 25 days. In accordance, nephronectin staining of lung and liver was preserved in animals injected with non-metastatic 67NR tumors. These results demonstrate that loss of nephronectin may play an important role in formation metastatic milieu for cancer cells. This is the first study demonstrating that tumor-induced loss of nephronectin expression in visceral organs in which metastatic growth takes place.

http://ift.tt/2wtZNNX

Risk of cause-specific death in individuals with cancer – modifying role diabetes, statins, and metformin

Abstract

Both diabetes mellitus (DM) and cancer are common diseases and they frequently occur in the same patients. We investigated the all-cause and cause-specific mortality dynamics in relation to baseline DM, statin use, and metformin use. The study population consisted of 39,900 incident cancer cases from Finland, 19,822 patients were free of DM at the start of follow-up, and 20,078 had DM. Mortality from all causes, and cancer, cardiovascular (CVD) and other causes was analysed using Poisson regression model with the following variables: sex, age, DM, statin and metformin usage in baseline, cancer type and stage, and calendar period. Statin usage was associated with a reduced cancer-specific mortality with incidence rate ratio (IRR) 0.72 (95% confidence interval 0.69-0.74), IRR for CVD mortality was 0.95 (0.88-1.02), and for other causes 0.64 (0.56-0.74). In a sub-population of DM patients, IRR for metformin in all-cause mortality was 0.74 (0.71-0.78), in cancer mortality 0.75 (0.72-0.79), in CVD mortality 0.75 (0.68-0.83), and other causes 0.68 (0.60-0.78). In conclusion, our register-based study of survival after cancer diagnosis showed that patients with diabetes had substantially poorer outcome in all measures. An association between baseline statin usage and lower all-cause, cancer, and cardiovascular mortality was modified by cancer type. The effect of statin use was largest for breast and colorectal cancer. Metformin usage in a subpopulation of oral antidiabetic users was in general associated with lower mortality, but this association was modified by cancer type. The association was strongest for liver, colorectal, and breast cancer. This article is protected by copyright. All rights reserved.

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Lifelong occupational exposure to wood dust and risk of nasal and nasopharyngeal cancer: A case-control study among men in four Nordic countries – with an emphasis on nasal adenocarcinoma

Abstract

The current study aims to provide stronger evidence to aid in our understanding of the role of lifelong occupational exposure to (softwood-dominated) mixed wood dust in aetiology of nasal cancer. We included broad exposure occurred in a range of wood-processing occupation across varied industries in four Nordic countries. A population-based case-control study was conducted on all male cases with nasal adenocarcinoma (393 cases), other types of nasal cancer (2446), and nasopharyngeal cancer (1747) diagnosed in Finland, Sweden, Norway, and Iceland between1961 and 2005. For each case, five male controls, who were alive at the time of diagnosis of the case (index date), were randomly selected, matched by birth-year and country. Cumulative exposures (CE)s to wood dust and formaldehyde before the index date were quantified based on a job-exposure matrix linked to occupational titles derived from population censuses. Hazard ratios (HRs) for the CE of wood dust were estimated by conditional logistic regression, adjusted for CE to formaldehyde and 95% confidence intervals (CIs) were calculated. There was an increasing risk of nasal adenocarcinoma related to wood dust exposure. The HR in the highest CE category of wood dust (≥ 28.82 mg/m³-years) was 16.5 (95% CI 5.05-54.1). Neither non-adenocarcinoma of the nose nor nasopharyngeal cancer could be linked to wood dust exposure. Lifelong CE to softwood-dominated mixed wood dusts is strongly linked with elevated risk in nasal adenocarcinoma but not with other types of nasal or nasopharyngeal cancer. This article is protected by copyright. All rights reserved.

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Coping and resiliency enhancement program (CARE): a pilot study for interpreters in cancer care

Abstract

Objective

There is a growing demand for interpreters in the cancer setting. Interpreters, the link to quality care for limited English proficiency patients, face many psychosocial stressors in their work. This project assessed interpreters' experiences of stress and piloted a resiliency program to help interpreters cope with stressors.

Methods

From 2013 to 2014, we pilot tested a targeted resiliency program with interpreters from three Boston-based hospitals. In Phase 1, we conducted five focus groups (n = 31) to identify interpreters' psychosocial needs. In Phase 2, we developed and tested a 4-h group program with 29 interpreters (response rate = 90%; 69% female, 54% Hispanic, 85% born outside of the U.S.).

Results

Phase 1. Stressors were patient-based (seeing young patients decline), interactions with medical team (unsure of role), and systems-based (appointment unpredictability). Phase 2. At baseline interpreters reported low abilities to cope with stress (measured by the Measure of Current Status (MOCS-A)). At 4-week follow-up we found improvements in job satisfaction (p = .02; Cohen's d = .41) and declines in sick days (p = .08; Cohen's d = .38). Stress reactivity (MOCS-A) improved; specifically participants reported feeling more assertive about their needs (p = .10; Cohen's d = .30) and more able to relax at will (p = .10; Cohen's d = .35)—important mechanisms to lower distress.

Conclusions

We piloted a resiliency program for medical interpreters in cancer care. We found that interpreters experience distress and have low coping skills. This program resulted in improved work factors and stress reactivity. Future research should include further implementation and testing in a larger, randomized trial.Copyright © 2016 John Wiley & Sons, Ltd.

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Efficacy of Extended Adjuvant Therapy with Aromatase Inhibitors in Early Breast Cancer among Common Clinicopathologically-defined Subgroups: A Systematic Review and Meta-analysis

Publication date: Available online 24 August 2017
Source:Cancer Treatment Reviews
Author(s): Hadar Goldvaser, Ibrahim AlGorashi, Domen Ribnikar, Bostjan Seruga, Arnoud J. Templeton, Alberto Ocana, Eitan Amir
BackgroundRandomized controlled trials (RCTs) have shown improvements in breast cancer outcomes from extending treatment with aromatase inhibitors (AIs) beyond the initial 5 years after diagnosis. Consistency of this effect in common clinicopathologically defined subgroups was not been reported systematically.MethodsWe identified RCTs comparing extended AIs to placebo or no treatment using a systematic search of MEDLINE and a review of abstracts from key conferences between 2013 and 2016. Hazard ratios (HRs) and 95% confidence intervals (CI) for disease-free survival (DFS) were included in a meta-analysis using generic inverse variance and random effects modelling. Pre-specified subgroups included: age (<60 ±5 years versus ≥60 ±5 years), tumor size (>2cm versus ≤2cm), nodal status (positive versus negative), hormone receptor status (double versus single receptor expression) and receipt of adjuvant chemotherapy (yes versus no).ResultsSeven trials comprising 16,349 patients were analyzed. Overall, the effect of extended AIs was similar in all subgroups. Non-significantly greater effect sizes were seen in patients with larger tumors (HR for DFS 0.77 versus 0.88, p for difference=0.44), nodal involvement (HR=0.72 versus 0.83, p for difference=0.22), double hormone receptor expression (HR=0.68 versus 1.01, p for difference=0.31) and receipt of adjuvant chemotherapy (HR=0.71 versus 0.80, p for difference=0.51).ConclusionsExtended treatment with AIs is associated with similar relative improvements in DFS in all subgroups analyzed. The combination of greater effect size and higher absolute risk of recurrence in node positive and larger tumors will likely translate to higher absolute benefits from extended AIs in these groups.



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Hospital quality factors influencing the mobility of patients for radical prostate cancer radiotherapy: a national population based study

Publication date: Available online 24 August 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Ajay Aggarwal, Daniel Lewis, Arunan Sujenthiran, Susan C. Charman, Richard Sullivan, Heather Payne, Malcolm Mason, Jan van der Meulen
IntroductionPatient choice policies have been introduced across publicly funded health systems to give patients more control over their care, and to encourage quality improvement amongst providers. To date we have no empirical evidence that patients requiring radiation treatment are prepared to travel to alternative more distant centres or the factors that influence this.Materials and MethodsWe present the results of a national cohort study using administrative hospital data for all 44,363 men who were diagnosed with prostate cancer and underwent radical radiotherapy in the English National Health Service between 2010 and 2014. Using geographic information systems we investigated the extent to which men choose to travel beyond ("bypass") their nearest radiotherapy centre and conditional logistic regression to estimate the effect of hospital and patient characteristics on this mobility.Results20.7% (n= 9,161) of men bypassed their nearest radiotherapy centre. Travel time had a very strong impact on where patients moved to for their treatment, but its effect was smaller for men who were younger, more affluent, and from rural areas (p for interaction always <0·001). Men were prepared to travel further to hospitals that offered hypofractionated prostate radiotherapy as their standard schedule (odds ratio 3.19, p<0.001), to large-scale radiotherapy units (odds ratio 1.56 P<0.001) and to hospitals that were early adopters of intensity modulated radiotherapy (odds ratio 1.37, p<0.001).ConclusionMen with prostate cancer are prepared to bypass their nearest radiotherapy centres. They are more likely to travel to larger established centres and those that offer innovative technology and more convenient radiotherapy schedules. Indicators, which accurately reflect the quality of radiotherapy delivered are needed to guide patients' choices for radiotherapy treatment. In their absence, patient mobility may negatively affect the efficiency and capacity of a regional or national radiotherapy service and offer perverse incentives for technology adoption.

Teaser

Using geographic information systems and econometric modelling we present the first national study evaluating the hospital quality factors that attract patients for radiotherapy treatment in health-care markets. We found that one in five men bypassed their nearest radiotherapy centre for treatment, especially those who were younger, and more affluent. In the absence of indicators reflecting treatment quality, centres that were early adopters of intensity modulated radiotherapy or that offered shorter hypofractionated treatment schedules were more attractive to patients.


http://ift.tt/2wtAJGZ

Identification of patients with localized Ewing sarcoma at higher risk for local failure: A report from the Children’s Oncology Group

Publication date: Available online 24 August 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Safia K. Ahmed, R. Lor Randall, Steven G. DuBois, William S. Harmsen, Mark Krailo, Karen J. Marcus, Katherine A. Janeway, David S. Geller, Joel I. Sorger, Richard B. Womer, Linda Granowetter, Holcombe E. Grier, Richard G. Gorlick, Nadia N.I. Laack
PurposeTo identify clinical and treatment variables associated with a higher risk of local failure in Ewing sarcoma patients treated on recent Children's Oncology Group protocols.Methods and MaterialsData for 956 patients treated with ifosfamide and etoposide based chemotherapy on INT-0091, INT-0154, and AEWS0031 were analyzed. Local treatment modalities were defined as surgery, definitive radiotherapy (RT), or surgery+radiation (S+RT). Five-year cumulative incidence of local failure was determined.ResultsThe local failure rate for the entire cohort was 7.3%, with a 3.9% rate for surgery, 15.3% for RT (p<0.01), and 6.7% for S+RT (p=0.12). The local failure incidence was 5.4% for extremity tumors, 13.2% for pelvis tumors (p<0.01), 5.3% for axial non-spine tumors (p=0.90), 9.1% for extraskeletal tumors (p=0.08), and 3.6% for spine tumors (p=0.49). The incidence of local failure was 14.8% for extremity tumors and 22.4% for pelvis tumors treated with RT, compared to 3.7% for extremity tumors and 3.9% for pelvis tumors treated with surgery (p≤0.01). There was no difference in local failure incidence by local treatment modality for axial non-spine, spine, and extraskeletal tumors. The local failure incidence was 11.9% in patients ≥18 years versus 6.7% in patients <18 years (p=0.02). Age ≥18 years (Hazard ratio 1.9, p=0.04) and treatment with RT (Hazard ratio 2.40, p<0.01) remained independent prognostic factors for higher local failure incidence on multivariate analysis. Tumor size (</≥ 8 centimeters) was available in 40% of patients and did not correlate with local failure incidence.ConclusionsLocal tumor control is excellent and similar between surgery and RT for axial non-spine, spine, and extraskeletal tumors. Age ≥18 years and use of RT, primarily for pelvis and extremity tumors, are associated with the highest risk of local failure. Further efforts should focus on improving outcomes for these patients.

Teaser

Our analysis of local tumor control outcomes in 956 Ewing sarcoma patients demonstrates age ≥18 years and use of definitive radiotherapy, primarily for pelvis and extremity tumors, are associated with the highest risk of local failure. Local tumor control is excellent and similar between surgery and definitive radiotherapy for axial non-spine, spine, and soft tissue extraskeletal tumors.


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Radiotherapy deficiencies identified during on-site dosimetry visits by the IROC Houston QA Center

Publication date: Available online 24 August 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Stephen F. Kry, Lainy Dromgoole, Paola Alvarez, Jessica Leif, Andrea Molineu, Paige Taylor, David S. Followill
PurposeTo review the dosimetric, mechanical, and programmatic deficiencies most frequently observed during on-site visits of radiotherapy facilities by the Imaging and Radiation Oncology Core Houston office (IROC Houston).MethodsIROC Houston's findings between 2000 and 2014, including 409 institutions and 1020 linacs, were compiled. IROC Houston's on-site evaluation includes verification of absolute calibration (tolerance of ±3%), relative dosimetric review (tolerances of ±2% between TPS calculation and measurement), mechanical evaluation (including MLC and kV-MV evaluation against TG-142 tolerances), and general programmatic review (including institutional QA program versus TG-40 and TG-142).ResultsAn average of 3.1 deficiencies was identified at each institution visited, a number that has decreased slightly with time. The most common errors are tabulated, and include TG-40/TG-142 compliance (82% of institutions were deficient), small field size output factors (59% of institutions had errors ≥3%), and wedge factors (33% of institutions had errors ≥3%). Dosimetric errors of ≥10%, including in beam calibration, were seen at many institutions.ConclusionsThere is substantial room for improvement of both dosimetric and programmatic issues in radiotherapy, which should be a high priority for the medical physics community. Particularly relevant was suboptimal beam modeling in the treatment planning system and a corresponding failure to detect these errors by not including TPS data in the linac QA process.

Teaser

IROC Houston on-site visits of radiotherapy facilities includes an evaluation of beam calibration, relative dosimetry, mechanical checks, and other programmatic issues. The deficiencies identified over the past 15 years are compiled in this study, highlighting areas where problems are most often found (e.g., small field output factors, wedge factors, calibration, etc.). These areas should receive particular attention during beam modeling and machine QA by medical physicists to ensure optimal accuracy is achieved.


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Feasibility of pencil beam scanned Intensity Modulated Proton Therapy in breath-hold for locally-advanced non-small cell lung cancer

Publication date: Available online 24 August 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Jenny Gorgisyan, Per Munck af Rosenschold, Rosalind Perrin, Gitte F. Persson, Mirjana Josipovic, Maria Francesca Belosi, Svend Aage Engelholm, Damien C. Weber, Antony J. Lomax
PurposeThe feasibility of treating patients with locally-advanced non-small cell lung cancer (NSCLC) with pencil beam scanned intensity modulated proton therapy (IMPT) in breath-hold has been evaluated.Methods and MaterialsFifteen NSCLC patients previously treated to 66 Gy in 33 fractions with image-guided photon radiation therapy were included in this simulation study. In addition to a planning breath-hold CT scan prior to treatment start, six (median, range: 3-9) breath-hold CT scans per patient were acquired prospectively, throughout the course of the radiation therapy. Three field IMPT treatment plans were constructed based on the planning breath-hold CT scan and the 4D dose distributions were simulated, taking both the intra- and inter-fractional motion of the patient into account, in addition to the dynamic treatment delivery.ResultsThe median clinical target volume (CTV) V95% (the volume receiving 95% of the prescribed dose) was 99.8% and 99.7% for the planned and simulated dose distributions, respectively. For three patients (20%), the dose degradation was more than 5% and plan adjustment was needed. Dose degradation was significantly correlated to the change in water-equivalent path lengths (WEPL) (p<0.01) in terms of percentage of voxels with 3 mm undershoot on repeat CTs. The dose to the organs at risk was similar for planned and simulated dose distributions. Three or less breath-holds per field would be required for 12/15 patients, which is clinically feasible.ConclusionsFor 9/15 NSCLC patients, IMPT in breath-hold was both dosimetrically robust and feasible to deliver regarding the treatment time. Three patients would require plan adaption to meet the dosimetric criteria. WEPL is an indicator of plan robustness and should be considered for selection of patients for which the plan would require adaptation.



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Recommendations for the optimal radiation dose in patients with primary cutaneous anaplastic large cell lymphoma: A report of the Dutch Cutaneous Lymphoma Group

Publication date: Available online 24 August 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Rutger C. Melchers, Rein Willemze, Laurien A. Daniëls, Karen J. Neelis, Marcel W. Bekkenk, Ellen R.M. de Haas, Barbara Horvath, Michelle M. van Rossum, Cornelus J.G. Sanders, Berit Velstra, Joep C.J.M. Veraart, Rachel E.J. Roach, Maarten H. Vermeer, Koen D. Quint
ObjectiveTo determine the optimal radiation dose for treatment of primary cutaneous anaplastic large cell lymphoma (C-ALCL) with solitary or localized, multifocal or recurrent skin lesions.Materials and MethodsIn this multicenter study, patients with C-ALCL, who had been treated with radiotherapy (RT) between 1984 and 2016, were retrieved from the Dutch registry of cutaneous lymphomas. Distinction was made between patients first presenting with solitary or localized (n=63), with multifocal skin lesions (n=6), and patients with a skin relapse (n=22). Radiation doses, treatment response and follow-up were evaluated. Radiation doses were categorized in low-dose (≤20 Gy), intermediate dose (21-39 Gy) and high-dose (≥40 Gy).Results61/63 (97%) patients presenting with solitary or localized skin lesions showed a complete response (CR). There were no differences in CR between low-dose (16/17), intermediate dose (15/15) and high-dose RT (30/31). After a median follow-up of 46 months, 30 of 63 (48%) patients had a relapse, but infield relapses were never observed. Six out of 6 (100%) patients initially presenting with multifocal skin lesions showed a CR (3/3 low-dose, 2/2 intermediate dose, 1/1 high-dose). After a median follow-up of 27 months, 3 of 6 patients had a relapse. Treatment of 33 skin relapses in 22 patients showed no differences in CR between low-dose (18/19), intermediate dose (6/6) and high-dose radiotherapy (8/8).In the last ten years there has been a decrease in radiation dose used in the treatment of C-ALCL. Treatment of multifocal and recurrent lesions with a dose of 8 Gy (2x4 Gy) resulted in CR of 17/18 lesions.ConclusionOur results show that a radiation dose of 20 Gy (8x2.5 Gy) is effective in patients presenting with solitary or localized skin lesions. For patients with multifocal skin lesions and patients with a skin relapse, a dose of 8 Gy (2x4 Gy) may be sufficient.

Teaser

Radiotherapy is the first choice of treatment in primary cutaneous anaplastic large cell lymphoma (C-ALCL), but the optimal dose has yet to be defined. Based on the evaluation of 114 radiation fields in 78 C-ALCL patients, we recommend a dose of 20 Gy for the initial treatment of solitary or localized skin lesions and a dose of 8 Gy for initial treatment of multifocal lesions and for recurrent lesions.


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Treatment-related non-contiguous radiologic changes in children with diffuse intrinsic pontine glioma treated with expanded irradiation fields and antiangiogenic therapy

Publication date: Available online 24 August 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Zoltan Patay, Thomas E. Merchant, Rosa Nguyen, Christopher R. Pierson, Arzu Onar-Thomas, Alberto Broniscer
Among 23 children with diffuse intrinsic pontine glioma who were treated with small-molecule inhibitors and expanded-field local RT, we observed a high incidence of non-contiguous treatment-related abnormalities (NCTRAs) in the brain. On the basis of their imaging features and patterns, we speculate that NCTRA development was secondary to synergistic steno-occlusive vascular effects induced by the combination of expanded clinical target volume RT, potent antiangiogenic therapy, young age, and in one case, possibly a genetic predisposition.



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Unknown Primary Squamous Cell Carcinoma of the Neck

Publication date: Available online 24 August 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Kristen J. Otto, Jimmy J. Caudell




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Imaging Findings within the first 12 months of Hepatocellular Carcinoma treated with Stereotactic Body Radiation Therapy (SBRT)

Publication date: Available online 24 August 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Mishal Mendiratta-Lala, Everett Gu, Dawn Owen, Kyle C. Cuneo, Latifa Bazzi, Theodore S. Lawrence, Hero K. Hussain, Matthew S. Davenport
PurposeTo correlate the imaging findings of treated hepatocellular carcinoma (HCC) post stereotactic body radiation therapy (SBRT) with explant pathology and alpha-fetoprotein (AFP) response.MethodsFrom 2007-2015, of 146 patients treated with liver SBRT for Barcelona Clinic Liver Cancer (BCLC) Stage A hepatocellular carcinoma, 10 were identified with inclusion criteria and hadregular interval follow up MRI/triple phase CT and explant pathology or declining AFP values for radiology-pathology response correlation. Reference standards for successful response were: >90% necrosis on explant pathology or pre-treatment AFP >75 ng/mL normalizing to <10 ng/mL within 1 year post-SBRT without other treatment. Subjects were treated with 24-50 Gy in 3-5 fractions. Multiphasic MRI or CT was performed at 3, 6, 9 and 12 months post-SBRT was compared to pre-treatment imaging by two expert radiologists. Descriptive statistics were calculated.ResultsThere were 10 subjects with 10 treated HCCs, classified as 3 OPTN 5a, 4 OPTN 5b, and 3 OPTN 5x. All had successfully treated HCCs, based on explant pathology or declining AFP. Four of 10 HCCs had persistent central arterial hyperenhancement 3-12 months post-SBRT; persistent washout was common up to 12 months (9/10). 9/10 treated HCCs exhibited decreased size at 12 months. Liver parenchyma adjacent to the lesion showed early (3-6 months) hyperemia followed by late (6-12 months) capsular retraction and delayed enhancement. No patient had a significant decline in liver function.ConclusionIn the absence of increasing size, persistent central arterial hyperenhancement and washout can occur within the first 12 months post-SBRT in successfully treated HCCs, and may not represent residual viable tumor. Liver parenchyma adjacent to the treated lesion showed inflammation followed by fibrosis, without significant change in hepatic function. Until a radiological signature of tumor control is determined, freedom from local progression appears to be the best measure of HCC control after SBRT

Teaser

In the absence of increasing size, persistent arterial hyperenhancement with washout can occur within the first 12 months post-SBRT in successfully treated HCCs, and should not be confused with residual tumor. Liver parenchyma adjacent to the treated lesion showed inflammation followed by fibrosis, without significant change in hepatic function. Until a radiological signature of tumor control is determined, freedom from local progression appears to be the best measure of HCC control after SBRT.


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Modeling DNA damage-induced pneumopathy in mice: insight from danger signaling cascades

Radiation-induced pneumonitis and fibrosis represent severe and dose-limiting side effects in the radiotherapy of thorax-associated neoplasms leading to decreased quality of life or - as a consequence of treat...

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