Cancers, Vol. 10, Pages 145: [18F]FDG-PET/CT in Hodgkin Lymphoma: Current Usefulness and Perspectives

Cancers, Vol. 10, Pages 145: [18F]FDG-PET/CT in Hodgkin Lymphoma: Current Usefulness and Perspectives

Cancers doi: 10.3390/cancers10050145

Authors: Salim Kanoun Cedric Rossi Olivier Casasnovas

Functional imaging using 18-fluorodeoxyglycose ([18F]FDG) positron emission tomography combined with computed tomography (PET/CT) has become a major imaging modality in Hodgkin lymphoma. This imaging modality allows for a significant improvement in staging, increased sensitivity, which involves differentiating residual tumors from fibrosis during assessment, and highly impacts treatment decisions into new PET-driven strategies. This review presents the main scientific data concerning the current applications of [18F]FDG-PET/CT in Hodgkin lymphoma at baseline, interim, and the end of treatment evaluation along with the main PET-driven trials for therapeutic decisions. The emergence of total metabolic tumor volume as a new functional prognostic factor will also be discussed.

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Impact of timing of trastuzumab initiation on long-term outcome of patients with early-stage HER2-positive breast cancer: the “one thousand HER2 patients” project

Impact of timing of trastuzumab initiation on long-term outcome of patients with early-stage HER2-positive breast cancer: the "one thousand HER2 patients" project

Impact of timing of trastuzumab initiation on long-term outcome of patients with early-stage HER2-positive breast cancer: the "one thousand HER2 patients" project, Published online: 18 May 2018; doi:10.1038/s41416-018-0114-x

Impact of timing of trastuzumab initiation on long-term outcome of patients with early-stage HER2-positive breast cancer: the "one thousand HER2 patients" project

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Microbial networking in cancer: when two toxins collide

Microbial networking in cancer: when two toxins collide

Microbial networking in cancer: when two toxins collide, Published online: 18 May 2018; doi:10.1038/s41416-018-0101-2

Microbial networking in cancer: when two toxins collide

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Molecular analysis in liquid biopsies for diagnostics of primary central nervous system lymphoma: review of literature and future opportunities

Publication date: Available online 17 May 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Laura S. Hiemcke-Jiwa, Roos J. Leguit, Tom J. Snijders, N. Mehdi Jiwa, Jonas. J.W. Kuiper, Roel A. de Weger, Monique C. Minnema, Manon M.H. Huibers
Primary central nervous system lymphoma (PCNSL) is an aggressive lymphoma with a poor prognosis, for which accurate and timely diagnosis is of utmost importance. Unfortunately, diagnosis of PCNSL can be challenging and a brain biopsy (gold standard for diagnosis) is an invasive procedure with the risk of major complications. Thus, there is an urgent need for an alternative strategy to diagnose and monitor these lymphomas.Currently, liquid biopsies from cerebrospinal fluid (CSF) are used for cytomorphologic and flow cytometric analysis. Recently, new biomarkers such as genetic mutations and interleukins have been identified in these liquid biopsies, further expanding the diagnostic armamentarium.In this review we present an overview of genetic aberrations (>70) reported in this unique lymphoma. Of these genes, we have selected those that are reported in ≥3 studies. Half of the selected genes are implicated in the NFκB pathway (CARD11, CD79B, MYD88, TBL1XR1 and TNFAIP3), while the other half are not related to this pathway (CDKN2A, ETV6, PIM1, PRDM1 and TOX). Although this underlines the crucial role of the NFκB pathway in PCNSL, CD79B and MYD88 are at present the only genes mentioned in liquid biopsy analysis.Finally, a stepwise approach is proposed for minimally invasive liquid biopsy analysis and work-up of PCNSL, incorporating molecular analysis. Prioritization and refinements of this approach can be constructed based upon multidisciplinary collaboration as well as novel scientific insights.



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A network meta-analysis of the treatments for esophageal squamous cell carcinoma in terms of survival

Publication date: Available online 17 May 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Amin Doosti-Irani, Kourosh Holakouie-Naieni, Abbas Rahimi-Foroushani, Mohammad Ali Mansournia, Peiman Haddad
We aimed to compare treatments for patients with esophageal squamous cell carcinoma (SCC) in terms of survival.Medline, Web of Science, Scopus, the Cochrane Library and Embase were searched. Randomized controlled trials (RCT) that had compared esophageal SCC treatments were included. The hazard ratio (HR) with 95% credible interval (CrI) was used to summarize the effect measures in the Bayesian network meta-analysis.Out of 23256 references, 43 RCTs with 34 treatments were included. Carboplatin and paclitaxel plus radiotherapy plus surgery (carbo-pacli + RT + S) compared with surgery alone decreased risk of death (HR = 0.49; 95% CrI: 0.26, 0.90). The HRs for carbo-pacli + RT + S versus surgery plus cisplatin and fluorouracil and surgery plus cisplatin and vindesine were 0.44 (0.22, 0.86) and 0.41 (0.20, 0.83), respectively. Among all treatments in network, carbo-pacli + RT + S ranked as first treatment.It seems carbo-pacli + RT + S was a better treatment among available treatments in network in terms of survival in patients with esophageal SCC.



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Long-term survival after liver metastasectomy in gastric cancer: Systematic review and meta-analysis of prognostic factors.

Publication date: Available online 17 May 2018
Source:Cancer Treatment Reviews
Author(s): Francesco Montagnani, Francesca Crivelli, Giuseppe Aprile, Caterina Vivaldi, Irene Pecora, Rocco De Vivo, Mario Alberto Clerico, Lorenzo Fornaro
BackgroundDespite the amelioration of systemic therapy, overall survival (OS) of metastatic gastric cancer (GC) patients remains poor. Liver is a common metastatic site and retrospective series suggest a potential OS benefit from hepatectomy, with interesting 5-year (5y) and 10-year (10y) OS rates in selected patients. We aim to evaluate the impact of liver resection and related prognostic factors on long-term outcome in this setting.MethodsWe searched Pubmed, EMBASE, and Abstracts/posters from international meetings since 1990. Data were extracted from publish papers. Random effects models meta-analyses and meta-regression models were built to assess 5yOS and the impact of different prognostic factor. Heterogeneity was assessed using between study variance, I² and Cochran's Q. Funnel plot were used to assess small study bias.ResultsThirty-three observational studies (for a total of 1304 patients) were included. Our analysis demonstrates a 5yOS rate of 22% (95%CI: 18%-26%) and 10yOS rate of 11% (95%CI: 7%-18%) among patients undergoing radical hepatectomy. A favorable effect on OS was shown by several factors linked to primary cancer (lower T and N stage, no lympho-vascular or serosal invasion) and burden of hepatic disease (≤3 metastases, unilobar involvement, greatest lesion <5 cm, negative resection margins). Moreover, lower CEA and CA19.9 levels and post-resection chemotherapy were associated with improved OS.ConclusionsSurgical resection of liver metastases from GC seems associated with a significant chance of 5yOS and 10yOS and compares favourably with results of medical treatment alone. Prospective evaluation of this approach and validation of adequate selection criteria are needed.



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Adjuvant NY-ESO-1 vaccine immunotherapy in high-risk resected melanoma: a retrospective cohort analysis

Abstract

Background

Cancer-testis antigen NY-ESO-1 is a highly immunogenic melanoma antigen which has been incorporated into adjuvant vaccine clinical trials. Three such early-phase trials were conducted at our center among patients with high-risk resected melanoma. We herein report on the pooled long-term survival outcomes of these patients in comparison to historical controls.

Methods

All melanoma patients treated at NYU Langone Health under any of three prospective adjuvant NY-ESO-1 vaccine trials were retrospectively pooled into a single cohort. All such patients with stage III melanoma were subsequently compared to historical control patients identified via a prospective institutional database with protocol-driven follow-up. Survival times were calculated using the Kaplan-Meier method, and Cox proportional hazard models were employed to identify significant prognostic factors and control for confounding variables.

Results

A total of 91 patients were treated with an NY-ESO-1 vaccine for the treatment of high-risk resected melanoma. Of this group, 67 patients were stage III and were selected for comparative analysis with 123 historical control patients with resected stage III melanoma who received no adjuvant therapy. Among the pooled vaccine cohort (median follow-up 61 months), the estimated median recurrence-free survival was 45 months, while the median overall survival was not yet reached. In the control cohort of 123 patients (median follow-up 30 months), the estimated median recurrence-free and overall survival were 22 and 58 months, respectively. Within the retrospective stage III cohort, NY-ESO-1 vaccine was associated with decreased risk of recurrence (HR = 0.56, p < 0.01) and death (HR = 0.51, p = 0.01). Upon controlling for sub-stage, the adjuvant NY-ESO-1 clinical trial cohort continued to exhibit decreased risk of recurrence (HR = 0.45, p < 0.01) and death (HR = 0.40, p < 0.01).

Conclusions

In this small retrospective cohort of resected stage III melanoma patients, adjuvant NY-ESO-1 vaccine immunotherapy was associated with longer recurrence-free and overall survival relative to historical controls. These data support the continued investigation of adjuvant NY-ESO-1 based immunotherapy regimens in melanoma.

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Kardioanästhesie: Monitoring und aktuelle hämodynamische Konzepte

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 332-345
DOI: 10.1055/s-0043-106281

Die Krankheitsschwere herzchirurgischer Patienten und die Komplexität der Eingriffe haben in den letzten Jahren deutlich zugenommen. Dies stellt nicht nur erhöhte Anforderungen an die neurologische und hämodynamische Überwachung, sondern macht es auch erforderlich, die hämodynamische Therapie – unter Berücksichtigung aktueller pharmakologischer Entwicklungen – individuell dem höheren Risikoprofil der Patienten anzupassen.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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Kasuistik: Metamizol-induzierte Agranulozytose

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 388-394
DOI: 10.1055/s-0043-115329

Metamizol hat insgesamt ein günstiges Nebenwirkungsprofil – aber es birgt ein höheres Risiko einer medikamenteninduzierten Agranulozytose als andere Schmerzmittel und darf daher nicht unkritisch eingesetzt werden. Dieser Beitrag berichtet von einem Patienten, der nach prothetischem Hüftersatz eine medikamenteninduzierte Agranulozytose – mutmaßlich durch Metamizol – entwickelt und trotz maximaler Therapie im septischen Schock verstirbt.
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Georg Thieme Verlag KG Stuttgart · New York

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Intensivmedizin: Ist ein hohes CRP ein geeigneter Prädiktor für ein postoperatives Delir?

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 324-327
DOI: 10.1055/a-0607-6157

Georg Thieme Verlag KG Stuttgart · New York

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Kardioanästhesie: Monitoring der Gerinnung und Gerinnungstherapie

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 364-379
DOI: 10.1055/s-0043-112099

Die Transfusion von allogenen Blutprodukten ist mit einer Erhöhung der perioperativen Morbidität und Letalität assoziiert. Störungen der Hämostase sind insbesondere bei kardiochirurgischen Patienten häufig anzutreffen und können zu transfusionspflichtigen Blutungen führen. Eine zielgerichtete Therapie der häufig komplexen Gerinnungsstörungen erfordert eine differenzierte Diagnostik.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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Kolloide zur Volumentherapie nach Verbrennung geeignet?

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 324-324
DOI: 10.1055/a-0607-6170

Georg Thieme Verlag KG Stuttgart · New York

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Kardioanästhesie 2018 – Wandel als Chance?

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 329-330
DOI: 10.1055/a-0588-4274

Georg Thieme Verlag KG Stuttgart · New York

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Hypertone Lösungen bei hämorrhagischem Schock ohne gesicherten Vorteil

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 327-328
DOI: 10.1055/a-0607-6183

Georg Thieme Verlag KG Stuttgart · New York

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Kardioanästhesie: anästhesiologisches Management

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 346-362
DOI: 10.1055/s-0043-106337

Das anästhesiologische Management herzchirurgischer Patienten hat sich in den letzten Jahren deutlich weiterentwickelt. Diese Übersicht widmet sich vor allem folgenden Bereichen: pharmakologische Kardioprotektion bei herzchirurgischen Eingriffen, Narkosemanagement an der Herz-Lungen-Maschine, Protokolle der „Enhanced Recovery After Cardiac Surgery" sowie innovative minimalinvasive Operationsverfahren wie die kathetergestützte Aortenklappenimplantation.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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Hypotonie nach Spinalanästhesie zur Sectio: Noradrenalin oder Phenylephrin?

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 328-328
DOI: 10.1055/a-0607-6144

Georg Thieme Verlag KG Stuttgart · New York

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Obere Altersgrenze bei ambulanter Anästhesie: Möglichkeiten und Risiken

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 380-386
DOI: 10.1055/s-0042-124408

Zahlreiche Operationen werden heute auch noch in höherem Lebensalter ambulant durchgeführt. Dieser Übersichtsartikel stellt die Vorteile der ambulanten Anästhesie bei älteren Patienten dar, zeigt aber auch die Risiken einer zu frühen Entlassung auf. Für den klinischen Alltag werden praktische Hilfestellungen für die Patientenauswahl gegeben und Risikofaktoren für eine ungeplante stationäre Aufnahme identifiziert.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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Pssst … AINS-Secrets: heute aus der Urologie – TUR-Syndrom

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 395-398
DOI: 10.1055/s-0042-101662

Georg Thieme Verlag KG Stuttgart · New York

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Erratum: Atemwegsmanagement – der schwierige Atemweg beim thoraxchirurgischen Patienten

Anästhesiol Intensivmed Notfallmed Schmerzther
DOI: 10.1055/a-0613-2898

Georg Thieme Verlag KG Stuttgart · New York

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Sauerstoffgabe für die Mutter bei Kaiserschnitt und oxidativer Stress des Kindes

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 322-322
DOI: 10.1055/a-0607-6131

Georg Thieme Verlag KG Stuttgart · New York

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Interchangeability of counts of cases and hours of cases for quantifying a hospital's change in workload among four-week periods of 1 year

Recent studies have made longitudinal assessments of case counts using State (e.g., United States) and Provincial (e.g., Canada) databases. Such databases rarely include either operating room (OR) or anesthesia times and, even when duration data are available, there are major statistical limitations to their use. We evaluated how to forecast short-term changes in OR caseload and workload (hours) and how to decide whether changes are outliers (e.g., significant, abrupt decline in anesthetics).

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Issue Information

Pediatric Blood &Cancer, Volume 65, Issue 7, July 2018.


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Fixation and Spread of Somatic Mutations in Adult Human Colonic Epithelium

Publication date: Available online 17 May 2018
Source:Cell Stem Cell
Author(s): Anna M. Nicholson, Cora Olpe, Alice Hoyle, Ann-Sofie Thorsen, Teja Rus, Mathilde Colombé, Roxanne Brunton-Sim, Richard Kemp, Kate Marks, Phil Quirke, Shalini Malhotra, Rogier ten Hoopen, Ashraf Ibrahim, Cecilia Lindskog, Meagan B. Myers, Barbara Parsons, Simon Tavaré, Mark Wilkinson, Edward Morrissey, Douglas J. Winton
We investigated the means and timing by which mutations become fixed in the human colonic epithelium by visualizing somatic clones and mathematical inference. Fixation requires two sequential steps. First, one of approximately seven active stem cells residing within each colonic crypt has to be mutated. Second, the mutated stem cell has to replace neighbors to populate the entire crypt in a process that takes several years. Subsequent clonal expansion due to crypt fission is infrequent for neutral mutations (around 0.7% of all crypts undergo fission in a single year). Pro-oncogenic mutations subvert both stem cell replacement to accelerate fixation and clonal expansion by crypt fission to achieve high mutant allele frequencies with age. The benchmarking of these behaviors allows the advantage associated with different gene-specific mutations to be compared irrespective of the cellular mechanisms by which they are conferred.

Graphical abstract

Teaser

Winton and colleagues describe stem cell dynamics in normal human colon to identify the efficiency of clone fixation within the epithelium and the rate of subsequent lateral expansion. Against these benchmarks biased stem cell behaviors advantaged in both fixation and expansion can be quantified to predict the age-related burden of pro-oncogenic mutation.


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High-Throughput Screening Enhances Kidney Organoid Differentiation from Human Pluripotent Stem Cells and Enables Automated Multidimensional Phenotyping

Publication date: Available online 17 May 2018
Source:Cell Stem Cell
Author(s): Stefan M. Czerniecki, Nelly M. Cruz, Jennifer L. Harder, Rajasree Menon, James Annis, Edgar A. Otto, Ramila E. Gulieva, Laura V. Islas, Yong Kyun Kim, Linh M. Tran, Timothy J. Martins, Jeffrey W. Pippin, Hongxia Fu, Matthias Kretzler, Stuart J. Shankland, Jonathan Himmelfarb, Randall T. Moon, Neal Paragas, Benjamin S. Freedman
Organoids derived from human pluripotent stem cells are a potentially powerful tool for high-throughput screening (HTS), but the complexity of organoid cultures poses a significant challenge for miniaturization and automation. Here, we present a fully automated, HTS-compatible platform for enhanced differentiation and phenotyping of human kidney organoids. The entire 21-day protocol, from plating to differentiation to analysis, can be performed automatically by liquid-handling robots, or alternatively by manual pipetting. High-content imaging analysis reveals both dose-dependent and threshold effects during organoid differentiation. Immunofluorescence and single-cell RNA sequencing identify previously undetected parietal, interstitial, and partially differentiated compartments within organoids and define conditions that greatly expand the vascular endothelium. Chemical modulation of toxicity and disease phenotypes can be quantified for safety and efficacy prediction. Screening in gene-edited organoids in this system reveals an unexpected role for myosin in polycystic kidney disease. Organoids in HTS formats thus establish an attractive platform for multidimensional phenotypic screening.

Graphical abstract

Teaser

Organoids derived from human iPSCs have great potential for drug screening, but their complexity poses a challenge for miniaturization and automation. Freedman and colleagues establish a robotic pipeline to manufacture and analyze kidney organoids in microwell arrays. They apply this system to improve differentiation, measure toxicity, and comprehend disease.


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Epithelial Sodium Channel Regulates Adult Neural Stem Cell Proliferation in a Flow-Dependent Manner

Publication date: Available online 17 May 2018
Source:Cell Stem Cell
Author(s): David Petrik, Michael H. Myoga, Sofia Grade, Niklas J. Gerkau, Melanie Pusch, Christine R. Rose, Benedikt Grothe, Magdalena Götz
One hallmark of adult neurogenesis is its adaptability to environmental influences. Here, we uncovered the epithelial sodium channel (ENaC) as a key regulator of adult neurogenesis as its deletion in neural stem cells (NSCs) and their progeny in the murine subependymal zone (SEZ) strongly impairs their proliferation and neurogenic output in the olfactory bulb. Importantly, alteration of fluid flow promotes proliferation of SEZ cells in an ENaC-dependent manner, eliciting sodium and calcium signals that regulate proliferation via calcium-release-activated channels and phosphorylation of ERK. Flow-induced calcium signals are restricted to NSCs in contact with the ventricular fluid, thereby providing a highly specific mechanism to regulate NSC behavior at this special interface with the cerebrospinal fluid. Thus, ENaC plays a central role in regulating adult neurogenesis, and among multiple modes of ENaC function, flow-induced changes in sodium signals are critical for NSC biology.

Graphical abstract

Teaser

Stem cells need to adapt to signals from the environment to regulate their output. Here, we show the key role of a flow-sensitive ion channel in regulating the activation of adult neural stem cells and their output.


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Microbial networking in cancer: when two toxins collide

https://ift.tt/2wTGpLK

European cancer mortality predictions for the year 2018 with focus on colorectal cancer

Abstract

Background

We projected cancer mortality statistics for 2018 for the European Union (EU) and its six more populous countries, using the most recent available data. We focused on colorectal cancer.

Materials and methods

We obtained cancer death certification data from stomach, colorectum, pancreas, lung, breast, uterus, ovary, prostate, bladder, leukaemia, and total cancers from the World Health Organisation database and projected population data from Eurostat. We derived figures for France, Germany, Italy, Poland, Spain, the UK, and the EU in 1970–2012. We predicted death numbers by age group and age-standardized (world population) rates for 2018 through joinpoint regression models.

Results

EU total cancer mortality rates are predicted to decline by 10.3% in men between 2012 and 2018, reaching a predicted rate of 128.9/100 000, and by 5.0% in women with a rate of 83.6. The predicted total number of cancer deaths is 1 382 000 when compared with 1 333 362 in 2012 (+3.6%). We confirmed a further fall in male lung cancer, but an unfavourable trend in females, with a rate of 14.7/100 000 for 2018 (13.9 in 2012, +5.8%) and 94 500 expected deaths, higher than the rate of 13.7 and 92 700 deaths from breast cancer. Colorectal cancer predicted rates are 15.8/100 000 men (−6.7%) and 9.2 in women (−7.5%); declines are expected in all age groups. Pancreatic cancer is stable in men, but in women it rose +2.8% since 2012. Ovarian, uterine and bladder cancer rates are predicted to decline further. In 2018 alone, about 392 300 cancer deaths were avoided compared with peak rates in the late 1980s.

Conclusion

We predicted continuing falls in mortality rates from major cancer sites in the EU and its major countries to 2018. Exceptions are pancreatic cancer and lung cancer in women. Improved treatment and—above age 50 years—organized screening may account for recent favourable colorectal cancer trends.

https://ift.tt/2wRUt8j

Taking it in the chin: vitamin K1 for the prevention of acneiform rash

In this issue of Annals of Oncology, Hofheinz et al. study the efficacy of a topical formulation of vitamin K1 in the prevention of a disfiguring toxicity resulting from epidermal growth factor receptor (EGFR) inhibitors [1]. An acneiform rash on the face and upper body develops in the majority of patients treated with EGFR inhibitors [2]. In addition to its psychosocial impact [3], it is associated with symptoms of pruritus and pain, may result in secondary infections [4], all of which may lead to inconsistencies in the dosing of causal anticancer agents [5]. Since the rash has been correlated with antitumor efficacy across most solid tumors in which it has been employed [6], mitigating this untoward event has been the subject of research for the past 15 years.

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Targeting cell cycle dependencies represent a novel therapeutic approach for selected sarcoma subgroups

Adult soft tissue sarcoma (STS) represents a group of rare malignant tumours associated with a very poor prognosis in the metastatic setting, with <20% of patients surviving 5 years after diagnosis [1]. Beyond their biological aggressiveness, under-recognition misdiagnosis of STS also contributes to this increased mortality. Management by specialized multidisciplinary boards is recommended and improves patients' survival [2].

https://ift.tt/2wZPeDV

ESR1 and endocrine therapy resistance: more than just mutations

Estrogen receptor (ER)-positive breast cancer accounts for 70%–80% of all diagnosed breast cancers [1]. The adoption of endocrine therapies, including ER modulators/degraders (SERMs/SERDs), which antagonize ER, and aromatase inhibitors (AIs), which suppress estrogen synthesis, as the mainstay of treatment of ER-positive breast cancer patients has resulted in substantial survival benefit for patients with early stage disease [2]. Treating ER-positive metastatic breast cancer (MBC), however, remains a significant clinical challenge, due to the development of secondary resistance to all modalities of endocrine therapy [3]. Recently, studies have identified recurrent somatic mutations within the ligand-binding domain (LBD) of ESR1 (encoding ER) in >30% of ER-positive MBC [4–8]. These mutations alter the conformation of ER and produce a constitutively active form of the protein. Mutations at residues 536–538, in particular, promote ER activity in the absence of ligand, resulting in resistance to AIs and reduced sensitivity to SERMs/SERDs [4, 5]. ESR1 fusion genes have also been reported in ER-positive MBCs; however, a detailed description of their manifestations and clinical prevalence is lacking [9]. In this issue of Annals of Oncology, Hartmaier et al. reported the identification of recurrent hyperactive ESR1 fusion genes in breast cancers resistant to endocrine therapy [10], adding to the diversity of reported ESR1 alterations.

https://ift.tt/2IMJ4vo

Time is up for PD-L1 testing standardization in lung cancer

The treatment options for patients with advanced non-small-cell lung carcinoma have undergone major changes in the recent years, particularly after the FDA approval of PD-1/PD-L1 immune checkpoint inhibitors nivolumab, pembrolizumab and atezolizumab) [1–8]. Each PD-1/PD-L1 inhibitor was approved together with a specific PD-L1 immunohistochemistry assay used in the clinical trials. In addition to unique primary antibody, each assay is optimized for use with a different detection system (i.e. Dako Link 48 and Ventana BenchMark) and a different diagnostic kit. Furthermore, the unique scoring algorithms for immunohistochemical assays were co-developed with each immune checkpoint inhibitor based on predictive values shown in the clinical trials. The one drug–one assay approach is challenging to implement in clinical practice as most laboratories do not use all of the staining platforms and such practice leads to avoidable escalation of laboratory testing cost and health care in general. The main question is whether laboratories will make effort to implement the FDA approved predictive assays for one or more anti-PD-1/PD-L1 checkpoint inhibitors or implement one or more affordable laboratory developed tests (LDTs) using already available testing platforms. To find the answer to this question it is essential to determine analytical concordance between commercially available PD-L1 immunohistochemical assays. Several studies showed an excellent analytical concordance between either FDA approved or LDTs [9–13]. Three assays SP263, 22C3 and 28-8 showed a high concordance in percentage of PD-L1 membrane staining of tumor cells at any intensity. In contrast, lower expression of PD-L1 on tumor cells was observed with SP142 clone. In terms of interpretation, interobserver concordance was high for tumor cell PD-L1 expression, while it was low for immune cells.

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Open-label randomised phase III trial of vinflunine versus an alkylating agent in patients with heavily pretreated metastatic breast cancer

Abstract

Background

There is no standard treatment after progression on second-line chemotherapy for metastatic breast cancer (MBC). We compared vinflunine with physician's choice of alkylating agent (AA) for patients with heavily pretreated MBC.

Patients and methods

In this open-label phase III trial, patients with MBC were included if they had received at least two prior chemotherapy regimens for MBC and had received anthracycline, taxane, antimetabolite and vinca alkaloid therapy. Patients were no longer candidates for these chemotherapies because of resistance and/or intolerance. Patients were randomised to either vinflunine 280 mg/m² intravenously every 3 weeks (q3w) or AA monotherapy q3w. Stratification factors were performance status, number of prior chemotherapy lines for MBC, disease measurability and study site. The primary end point was overall survival (OS).

Results

A total of 594 patients were randomised (298 to vinflunine, 296 to AA). There was no difference between treatment arms in OS (hazard ratio 1.04, P = 0.67; median 9.1 months for vinflunine versus 9.3 months for AA), progression-free survival (hazard ratio 0.94, P = 0.49; median 2.5 versus 1.9 months, respectively) or overall response rate (6% versus 4%, respectively). However, the disease control rate was significantly higher with vinflunine than AA (44% versus 35%, respectively; P = 0.04). The most common adverse events (any grade) were haematological and gastrointestinal disorders and asthenia in both arms. The most common grade 3/4 adverse events were neutropenia (19% versus 11% with vinflunine versus AA, respectively) and asthenia (10% versus 4%).

Conclusions

Vinflunine 280 mg/m² q3w did not improve OS compared with the physician's choice of AA as third- or later-line therapy for MBC. Vinflunine demonstrated an acceptable safety profile, suggesting that vinflunine 320 mg/m² merits evaluation.

ClinicalTrials.gov

NCT01091168.

https://ift.tt/2rRoC1L

Computational prediction of neoantigens: do we need more data or new approaches?

The capability of the immune system for self-recognition has recently become the focus of interest for a broadening research community due to the impressive clinical results achieved with immune checkpoint inhibitors and other immunotherapies in the treatment of advanced metastatic carcinoma [1]. A significant portion of this clinical efficacy is attributed to the fact that the genomic instability of cancer generates mutation-derived peptides (neopeptides) that are not present in normal cells. A subset of these neopeptides may be neoantigens (also called neoepitopes) which are recognized as alien by cytotoxic T cells. Ideally, a cell producing neoantigens should be eliminated by the immune system. However, tumors are able to inhibit this immune response by activating various checkpoint mechanisms; these can be overcome by the now widely used therapeutic agents of checkpoint inhibitors such as anti PD-L1 or anti-CTLA-4 antibodies. There is increasing evidence that such neoantigen-driven immune responses are responsible for the significant clinical response shown to immune checkpoint inhibitors in at least one specific type of tumors, microsatellite instable cancer [2, 3].

https://ift.tt/2k845Tt

Toward optimizing outcomes in Her2-positive gastric cancer: timing and genomic context matter

In 2010, the ToGA trial demonstrated a 2.7-month improvement in overall survival (OS) with the addition of the anti-HER2 monoclonal antibody trastuzumab to platinum-5-FU in first-line treatment of advanced HER2-positive gastric cancer [1]. Subsequent attempts to address HER2-directed therapies in first and second lines have been met with largely disappointing results [2–5]. In the phase III LOGiC trial, the addition of the small molecule HER2-inhibitor lapatinib to first-line CapeOx failed to improve OS in the primary efficacy population (12.2 versus 10.5, Hazard Ratio (HR) 0.91, P = 0.35), though preplanned subset analysis suggested a benefit with the addition of lapatinib in Asian patients (HR 0.68) and patients < 60 years old (HR 0.69) [2]. There was no correlation between Immunohistochemistry (IHC)-status and OS benefit in the study population, which were all amplified by FISH. Contemporary with the LOGiC trial was several publications associating magnitude of HER2 amplification with degree of benefit from trastuzumab, as well as the recognition that HER2-positive gastric cancer is a highly heterogeneous disease complicated by chronologic HER2 changes, and inter- and intratumoral variations in molecular features [6–9]. The incorporation of cell-free DNA (cfDNA) has allowed for perhaps more representative sampling of global tumor makeup, potentially facilitating identification of patient subsets with better or worse outcomes though limited prospective data exist in esophagogastric cancers [10].

https://ift.tt/2rPXvEw

Introducing whole-genome sequencing into routine cancer care: the Genomics England 100 000 Genomes Project

Large-scale sequencing studies such as the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) have begun to catalogue the spectra of somatic mutations present in different solid tumour types [1, 2]. However, to date there has been minimal traction for solid tumours in alignment of large-scale sequencing data to longitudinal data on therapy and outcome. Such data are essential if we are to better target conventional cytotoxics, as well as emerging drugs such as immunotherapeutics. Stratification using molecular markers could improve benefit against cost and side-effects, especially critical in the adjuvant setting. Molecular heterogeneity of tumours and confounding patient factors mean datasets of daunting size and depth will be required. Arguably these will only be achieved through molecular analyses as standard for cancer patients entering clinical trials and, by adopting a population level approach to molecular analysis of patients undergoing routine cancer treatments.

https://ift.tt/2k6qUXl

Overexpression of BLM promotes DNA damage and increased sensitivity to platinum salts in triple-negative breast and serous ovarian cancers

Abstract

Background

Platinum-based therapy is an effective treatment for a subset of triple-negative breast cancer and ovarian cancer patients. In order to increase response rate and decrease unnecessary use, robust biomarkers that predict response to therapy are needed.

Patients and methods

We performed an integrated genomic approach combining differential analysis of gene expression and DNA copy number in sensitive compared with resistant triple-negative breast cancers in two independent neoadjuvant cisplatin-treated cohorts. Functional relevance of significant hits was investigated in vitro by overexpression, knockdown and targeted inhibitor treatment.

Results

We identified two genes, the Bloom helicase (BLM) and Fanconi anemia complementation group I (FANCI), that have both increased DNA copy number and gene expression in the platinum-sensitive cases. Increased level of expression of these two genes was also associated with platinum but not with taxane response in ovarian cancer. As a functional validation, we found that overexpression of BLM promotes DNA damage and induces sensitivity to cisplatin but has no effect on paclitaxel sensitivity.

Conclusions

A biomarker based on the expression levels of the BLM and FANCI genes is a potential predictor of platinum sensitivity in triple-negative breast cancer and ovarian cancer.

https://ift.tt/2rR6WUa

Beyond second-line therapy in patients with metastatic colorectal cancer: a systematic review

Abstract

Background

The optimal chemotherapeutic regimen for use beyond the second line for patients with metastatic colorectal cancer (mCRC) remains unclear.

Materials and methods

We systematically searched the Cochrane Database of Systematic Reviews, EMBASE and Medline for records published between January 2002 and May 2017, and cancer congress databases for records published between January 2014 and June 2017. Eligible studies evaluated the efficacy, safety and patient-reported outcomes of monotherapies or combination therapies at any dose and number of treatment cycles for use beyond the second line in patients with mCRC. Studies were assessed for design and quality, and a qualitative data synthesis was conducted to understand the impact of treatment on overall survival and other relevant cancer-related outcomes.

Results

The search yielded 938 references of which 68 were included for qualitative synthesis. There was limited evidence to support rechallenge with chemotherapy, targeted therapy or both. Compared with placebo, an overall survival benefit for trifluridine/tipiracil (also known as TAS-102) or regorafenib has been shown for patients previously treated with conventional chemotherapy and targeted therapy. There was no evidence to suggest a difference in efficacy between these treatments. Patient choice and quality of life at this stage of treatment should also be considered when choosing an appropriate therapy.

Conclusions

These findings support the introduction of an approved agent such as trifluridine/tipiracil or regorafenib beyond the second line before any rechallenge in patients with mCRC who have failed second-line treatment.

https://ift.tt/2k5IPxn

Predictive biomarkers and EGFR inhibitors in squamous cell carcinoma of head and neck (SCCHN)

Squamous cell carcinoma of the head and neck (SCCHN) represents the sixth most common cancer globally and accounts for ∼5% of all cancers [1, 2]. The management of these cancers is complex and requires a multidisciplinary approach with multi-modality treatments but the survival outcome of these patients remain poor [2].

https://ift.tt/2Ipnm17

Lifestyle factors and risk of sporadic colorectal cancer by microsatellite instability status: a systematic review and meta-analyses

Abstract

Introduction

The association of lifestyle factors with molecular pathological subtypes of colorectal cancer (CRC), such as microsatellite instability (MSI), could provide further knowledge about the colorectal carcinogenic process. The aim of this review was to evaluate possible associations between lifestyle factors and risk of sporadic CRC by MSI status.

Methods

PubMed and Web of Science were searched for studies investigating the association between alcohol, body mass index, dietary fiber, hormone replacement therapy (HRT), non-steroidal anti-inflammatory drugs, physical activity, red meat, smoking, or statin use, with MSI-high (MSI-H) and microsatellite stable (MSS) CRC. Meta-analyses were carried out to calculate summary relative risks (sRR).

Results

Overall, 31 studies reporting on the association between lifestyle factors and CRC according to MSI status were included in this review. Ever smoking was associated with MSI-H (sRR = 1.62; 95% CI: 1.40–1.88) and MSS/MSI-low CRC (sRR = 1.10; 95% CI: 1.01–1.20), but the association was significantly stronger for MSI-H CRC. The use of HRT was associated with a 20% decrease (sRR = 0.80; 95% CI: 0.73–0.89) in the risk of MSS CRC, but was not associated with MSI-H CRC. An increase in body mass index per 5 kg/m² was equally associated with MSS and MSI-H CRC (sRR = 1.22, in both cases), but was statistically significant for MSS CRC only (95% CI: 1.11–1.34 and 0.94–1.58, respectively). Limited evidence for associations between other lifestyle factors and CRC by MSI status exists.

Conclusions

Lifestyle factors, such as HRT and smoking are differentially associated with the risk of MSI-H and MSS CRC. Further research on associations of lifestyle factors and CRC subtypes is necessary to provide a better understanding of the CRC disease pathway.

https://ift.tt/2k6YHQw

Management of metastatic retroperitoneal sarcoma: a consensus approach from the Trans-Atlantic Retroperitoneal Sarcoma Working Group (TARPSWG)†

Abstract

Introduction

Retroperitoneal sarcoma (RPS) is a rare disease accounting for 0.1%–0.2% of all malignancies. Management of RPS is complex and requires multidisciplinary, tailored treatment strategies at all stages, but especially in the context of metastatic or multifocal recurrent disease. Due to the rarity and heterogeneity of this family of diseases, the literature to guide management is limited.

Methods

The Trans-Atlantic Retroperitoneal Sarcoma Working Group (TARPSWG) is an international collaboration of sarcoma experts from all disciplines convened in an effort to overcome these limitations. The TARPSWG has compiled the available evidence surrounding metastatic and multifocally recurrent RPS along with expert opinion in an iterative process to generate a consensus document regarding the complex management of this disease. The objective of this document is to guide sarcoma specialists from all disciplines in the diagnosis and treatment of multifocal recurrent or metastatic RPS.

Results

All aspects of patient assessment, diagnostic processes, local and systemic treatments, and palliation are reviewed in this document, and consensus recommendations provided accordingly. Recommendations were guided by available evidence, in conjunction with expert opinion where evidence was lacking.

Conclusions

This consensus document combines the available literature regarding the management of multifocally recurrent or metastastic RPS with the practical expertise of high-volume sarcoma centers from multiple countries. It is designed as a tool for decision making in the complex multidisciplinary management of this condition and is expected to standardize management across centers, thereby ensuring that patients receive the highest quality care.

https://ift.tt/2rSK5HJ

Epigenetic modifiers as new immunomodulatory therapies in solid tumours

Abstract

Background

Immune therapies have revolutionized cancer treatment over the last few years by allowing improvements in overall survival. However, the majority of patients is still primary or secondary resistant to such therapies, and enhancing sensitivity to immune therapies is therefore crucial to improve patient outcome. Several recent lines of evidence suggest that epigenetic modifiers have intrinsic immunomodulatory properties, which could be of therapeutic interest.

Material and methods

We reviewed preclinical evidence and clinical studies which describe or exploit immunomodulatory properties of epigenetic agents. Experimental approaches, clinical applicability and corresponding ongoing clinical trials are described.

Results

Several epigenetic modifiers, such as histone deacetylase inhibitors, DNA methyl transferase inhibitors, bromodomain inhibitors, lysine-specific histone demethylase 1 inhibitors and enhancer of zeste homolog 2 inhibitors, display intrinsic immunomodulatory properties. The latter can be achieved through the action of these drugs either on cancer cells (e.g. presentation and generation of neoantigens, induction of immunogenic cell death, modulation of cytokine secretion), on immune cells (e.g. linage, differentiation, activation status and antitumor capability), or on components of the microenvironment (e.g. regulatory T cells and macrophages). Several promising combinations, notably with immune checkpoint blockers or adoptive T-cell therapy, can be envisioned. Dedicated clinically relevant approaches for patient selection and trial design will be required to optimally develop such combinations.

Conclusion

In an era where immune therapies are becoming a treatment backbone in many tumour types, epigenetic modifiers could play a crucial role in modulating tumours' immunogenicity and sensitivity to immune agents. Optimal trial design, including window of opportunity trials, will be key in the success of this approach, and clinical evaluation is ongoing.

https://ift.tt/2k6aqPd

Genetic profiling of cell-free DNA from cerebrospinal fluid: opening the barrier to leptomeningeal metastasis in EGFR-mutant NSCLC

Over the past decade, remarkable progress has been made in the management of advanced non-small-cell lung cancer (NSCLC), when tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors have been added to the therapeutic armamentarium. Indeed, dramatic responses to epidermal growth factor receptor (EGFR)-TKIs are observed in patients with NSCLC harbouring activating EGFR driver mutations [1, 2]. Unfortunately, all tumours ultimately develop secondary resistance, half of these due to the acquirement of the gatekeeper EGFR T790M mutation [3]. Fortunately, T790M-induced resistance can now be successfully addressed by use of third-generation EGFR-TKIs that show impressive activity in these patients [4].

https://ift.tt/2rRof7n

Statistical controversies in clinical research: limitations of open-label studies assessing antiangiogenic therapies with regard to evaluation of vascular adverse drug events—a meta-analysis

Abstract

Background

Previous meta-analyses have shown paradoxical increased risk of bleeding and thrombotic events in patients receiving antiangiogenics (AA) that may be simply explained by the studies design included. By a meta-epidemiological approach, we aim to investigate the impact of double-blind (DB) and open-label study designs on the risks of bleeding, venous thrombotic events (VTE) and arterial thrombotic events (ATE) in cancer patients treated with AA.

Materials and methods

We searched Medline, Cochrane, ClinicalTrials.gov databases and proceedings of major oncology congresses for clinical trials published from January 2003 to January 2016. Randomized clinical trials that assigned patients with solid cancers to AA or control groups were eligible for inclusion. Combined odds ratios (ORs) for the risks of bleeding events, VTE and ATE were calculated for open and DB trials. Estimation bias of the treatment effect was determined by the ratio of OR, by dividing the OR values obtained in open-label trials by those obtained in DB trials.

Results

The literature-based meta-analysis included 166 trials (72 024 patients). For bleeding events, comparison of AA versus control yielded an overall OR of 2.41 [95% confidence interval (95% CI) 2.12–2.73; P < 0.001], but this risk was overestimated by 1.68 (95% CI 1.33–2.13) in open-label studies. Concerning VTE, the OR was 1.19 (95% CI 1.04–1.35; P = 0.012) overall with AA, but this effect disappears when considering only DB trials (OR 0.99, 95% CI 0.83–1.17). The corresponding ratio of OR showed a significant overestimation of 1.53 (95% CI 1.19–1.96) in open-label trials. For ATE, an OR of 1.59 (95% CI 1.30–1.94; P < 0.001) was observed, associated with a significant overestimation of 1.65 (95% CI 1.13–2.43) in open-label trials.

Conclusions

Open-label studies overestimated the risk of vascular adverse events with AA by at least 50%. Meta-analyses assessing adverse drug events should therefore be restricted to DB randomized trials.

https://ift.tt/2k40y8m

Expression III: patients’ expectations and preferences regarding physician–patient relationship and clinical management—results of the international NOGGO/ENGOT-ov4-GCIG study in 1830 ovarian cancer patients from European countries

Abstract

Backround

The primary aim of this study was to investigate information needs and treatment preferences of patients with ovarian cancer, focusing especially on physician–patient relationship and treatment.

Patients and methods

A questionnaire was developed based on the experiences of the national German survey 'Expression II', and was provided to patients with ovarian cancer either at initial diagnosis or with recurrent disease via Internet (online-version) or as print-out-version.

Results

From December 2009 to October 2012, a total of 1830 patients with ovarian cancer from eight European countries (Austria, Belgium, France, Germany, Italy, Poland, Romania, Spain) participated, 902 (49.3%) after initial diagnosis and 731 (39.9%) with recurrent ovarian cancer. The median age was 58 years (range 17–89). Nearly all patients (96.2%) had experienced upfront surgery followed by first-line chemotherapy (91.8%). The majority of patients were satisfied with the completeness and comprehensibility of the explanation about the diagnosis and treatment options. The three most important aspects, identified by patients to improve the treatment for ovarian cancer included: 'the therapy should not induce alopecia' (42%), 'there must be more done to counter fatigue' (34.5%) and 'the therapy should be more effective' (29.7%). Out of 659 (36%) patients, who were offered participation in a clinical trial, 476 (26%) were included.

Conclusion

This study underlines the high need of patients with ovarian cancer for all details concerning treatment options irrespective of their cultural background, the stage of disease and the patient's age. Increased information requirements regarding potential side effects and treatment alternatives were recorded. Besides the need for more effective therapy, alopecia and fatigue are the most important side effects of concern to patients.

https://ift.tt/2rRcsWJ

Developing androgen receptor targeting for salivary gland cancers

Salivary gland cancers (SGCs) are rare malignancies that can arise from major (parotid, submandibular, sublingual) or minor glands present throughout the upper aerodigestive tract. These tumors encompass a diverse set of diseases representing more than 20 different histologic subtypes with distinct clinical behaviors, genomic/molecular profiles, and responsiveness to drug therapy [1–3]. Similar to other rare diseases, the lack of prospective drug trials focused on singular SGC tumor types makes evidence-based management a challenge.

https://ift.tt/2ka6OeN

Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases

Abstract

Background

Long-term data with immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) are limited. Two phase III trials demonstrated improved overall survival (OS) and a favorable safety profile with the anti-programmed death-1 antibody nivolumab versus docetaxel in patients with previously treated advanced squamous (CheckMate 017) and nonsquamous (CheckMate 057) NSCLC. We report results from ≥3 years' follow-up, including subgroup analyses of patients with liver metastases, who historically have poorer prognosis among patients with NSCLC.

Patients and methods

Patients were randomized 1 : 1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m² every 3 weeks) until progression or discontinuation. The primary end point of each study was OS. Patients with baseline liver metastases were pooled across studies by treatment for subgroup analyses.

Results

After 40.3 months' minimum follow-up in CheckMate 017 and 057, nivolumab continued to show an OS benefit versus docetaxel: estimated 3-year OS rates were 17% [95% confidence interval (CI), 14% to 21%] versus 8% (95% CI, 6% to 11%) in the pooled population with squamous or nonsquamous NSCLC. Nivolumab was generally well tolerated, with no new safety concerns identified. Of 854 randomized patients across both studies, 193 had baseline liver metastases. Nivolumab resulted in improved OS compared with docetaxel in patients with liver metastases (hazard ratio, 0.68; 95% CI, 0.50–0.91), consistent with findings from the overall pooled study population (hazard ratio, 0.70; 95% CI, 0.61–0.81). Rates of treatment-related hepatic adverse events (primarily grade 1–2 liver enzyme elevations) were slightly higher in nivolumab-treated patients with liver metastases (10%) than in the overall pooled population (6%).

Conclusions

After 3 years' minimum follow-up, nivolumab continued to demonstrate an OS benefit versus docetaxel in patients with advanced NSCLC. Similarly, nivolumab demonstrated an OS benefit versus docetaxel in patients with liver metastases, and remained well tolerated.

Clinical trial registration

CheckMate 017: NCT01642004; CheckMate 057: NCT01673867.

https://ift.tt/2rS074H

Radiation dose constraints for organs at risk in neuro-oncology; the European Particle Therapy Network consensus

For unbiased comparison of different radiation modalities and techniques, consensus on delineation of radiation sensitive organs at risk (OARs) and on their dose constraints is warranted. Following the publication of a digital, online atlas for OAR delineation in neuro-oncology by the same group, we assessed the brain OAR-dose constraints in a follow-up study.

https://ift.tt/2GthDBu

Valproate-induced hyperammonemia - uncovering an underlying inherited metabolic disorder: a case report

Sodium valproate is a commonly used anticonvulsant. It is widely recognized that valproate can cause hyperammonemia, particularly in people with underlying liver disease. Patients with urea cycle disorders are...

https://ift.tt/2rQFciA

Circulating Selenium and Prostate Cancer Risk: A Mendelian Randomization Analysis

Abstract

In the Selenium and Vitamin E Cancer Prevention Trial (SELECT), selenium supplementation (causing a median 114 μg/L increase in circulating selenium) did not lower overall prostate cancer risk, but increased risk of high-grade prostate cancer and type 2 diabetes. Mendelian randomization analysis uses genetic variants to proxy modifiable risk factors and can strengthen causal inference in observational studies. We constructed a genetic instrument comprising 11 single nucleotide polymorphisms robustly (P < 5 × 10^-8) associated with circulating selenium in genome-wide association studies. In a Mendelian randomization analysis of 72 729 men in the PRACTICAL Consortium (44 825 case subjects, 27 904 control subjects), 114 μg/L higher genetically elevated circulating selenium was not associated with prostate cancer (odds ratio [OR] = 1.01, 95% confidence interval [CI] = 0.89 to 1.13). In concordance with findings from SELECT, selenium was weakly associated with advanced (including high-grade) prostate cancer (OR = 1.21, 95% CI = 0.98 to 1.49) and type 2 diabetes (OR = 1.18, 95% CI = 0.97 to 1.43; in a type 2 diabetes genome-wide association study meta-analysis with up to 49 266 case subjects and 249 906 control subjects). Our Mendelian randomization analyses do not support a role for selenium supplementation in prostate cancer prevention and suggest that supplementation could have adverse effects on risks of advanced prostate cancer and type 2 diabetes.

https://ift.tt/2wQYEBh

Lifetime Smoking History and Risk of Lung Cancer: Results From the Framingham Heart Study

Abstract

Background

The relative risk of lung cancer decreases with years since quitting (YSQ) smoking, but risk beyond 25 YSQ remains unclear. Current lung cancer screening guidelines, which exclude smokers with more than 15 YSQ, may not detect lung cancers in this population.

Methods

We analyzed data from Framingham Heart Study Original (n = 3905) and Offspring cohort (n = 5002) participants for lifetime smoking and lung cancer incidence from 1954 to 1958 (Exam 4) and 1971 to 1975 (Exam 1), respectively, through 2013. We used multivariable-adjusted Cox proportional hazards regression models to compare current, former, and never smokers and lung cancer risk. Smoking status and covariates were time-updated every two years (Original) or four years (Offspring). Primary analyses were restricted to heavy ever smokers with more than 21.3 pack-years; additional analyses included all ever smokers.

Results

On follow-up (median = 28.7 years), 284 lung cancers were detected: incidence rates/1000 person-years in current, former, and never smokers were 1.97 (95% confidence interval [CI] = 1.66 to 2.33), 1.61 (95% CI = 1.34 to 1.93), and 0.26 (95% CI = 0.17 to 0.39), respectively. Heavy former (vs never) smokers had elevated lung cancer risk at all YSQ (<5: hazard ratio [HR] = 12.12, 95% CI = 6.94 to 21.17; 5–9: HR = 11.77, 95% CI = 6.78 to 20.45; 10–14: HR = 7.81, 95% CI = 3.98 to 15.33; 15–24: HR = 5.88, 95% CI = 3.19–10.83; ≥25: HR = 3.85, 95% CI = 1.80 to 8.26). Heavy former (vs current) smokers had 39.1% lower lung cancer risk within five YSQ. Among all former smokers, 40.8% of lung cancers occurred after more than 15 YSQ.

Conclusions

Among heavy former smokers, lung cancer risk drops within five YSQ relative to continuing smokers, yet it remains more than threefold higher than never smokers after 25 YSQ. Four of ten lung cancers occurred in former smokers with more 15 YSQ, beyond the screening window of the current guideline.

https://ift.tt/2IL5e0X

Lung Cancer Screening and Smoking Cessation: Never Too Early or Too Late

With lung cancer being the leading cause of cancer mortality worldwide, clinicians are eager for interventions that improve early detection (1). Lung cancer screening with low-dose computed tomography (LDCT) is now being broadly implemented across the United States (2,3). This is driven by results from the National Lung Screening Trial (NLST), which demonstrated three fewer deaths from lung cancer for every 1000 high-risk individuals who underwent screening with LDCT for three years, compared with three annual rounds of screening with chest radiography (4). Guidelines from multiple organizations including the United States Preventive Services Task Force (USPSTF), the American Cancer Society, and others now recommend lung cancer screening for high-risk patients, with eligibility criteria that are largely based on the NLST criteria (5). Importantly, the Centers for Medicare and Medicaid Services (CMS) now covers the cost of LDCT for current or former smokers who are 55 to 77 years old, have at least 30 pack-years of tobacco exposure, and still smoke or quit within the last 15 years.

https://ift.tt/2wPBcEA

Validation of the 16-Gene Recurrence Score in patients with locoregional, high-risk renal cell carcinoma from a phase 3 trial of adjuvant sunitinib

Purpose: Adjuvant sunitinib prolonged disease-free survival (DFS) (hazard ratio [HR] 0.76) in patients with locoregional high-risk renal cell carcinoma (RCC) in the S-TRAC trial (ClinicalTrials.gov NCT00375674). The 16-gene Recurrence Score(RS) assay was previously developed and validated to estimate risk for disease recurrence in patients with RCC post-nephrectomy. This analysis further validated the prognostic value of RS assay in patients from S-TRAC and explored association of RS results with prediction of sunitinib benefit. Experimental Design: The analysis was prospectively designed with prespecified genes, algorithm, endpoints, and analytical methods. Primary RCC was available from 212 patients with informed consent; primary analysis focused on patients with T3 RCC. Gene expression was quantitated by RT-PCR. Time to recurrence (TTR), DFS, and renal cancer-specific survival (RCSS) were analyzed using Cox proportional hazards regression. Results: Baseline characteristics were similar between patients with and without RS results, and between the sunitinib and placebo arms among patients with RS results. RS results predicted TTR, DFS, and RCSS in both arms, with the strongest results observed in the placebo arm. When high versus low RS groups were compared, HR for recurrence was 9.18 (95% CI, 2.15-39.24; P < 0.001) in the placebo arm; interaction of RS results with treatment was not significant. Conclusions: The strong prognostic performance of the 16-gene RS assay was confirmed in S-TRAC, and the RS assay is now supported by level IB evidence. RS results may help identify patients at high risk for recurrence who may derive higher absolute benefit from adjuvant therapy.

https://ift.tt/2Gv1E6c

Phase I study of oncolytic vaccinia virus GL-ONC1 in patients with peritoneal carcinomatosis

Objective: Peritoneal carcinomatosis (PC) is common in advanced tumor stages or disease recurrence arising from gastrointestinal cancers, gynecologic malignancies, or primary peritoneal carcinoma. Since current therapies are mostly ineffective, new thera­peutic approaches are needed. Here, we report on a phase I study designed to assess safety, MTD, and anti-tumor activity of intra­peri­toneal (i.p.) administration of oncolytic vaccinia virus GL-ONC1 in advanced stage PC patients. Design: GL-ONC1 was administered i.p. every four weeks for up to four cycles at three different dose levels (10⁷-10⁹ pfu) following a standard 3 + 3 dose escalation design. GL-ONC1 was infused via an indwelling catheter which enabled repetitive analyses of peritoneal fluid biopsies. The primary study objective was safety of GL-ONC1 according to Common Terminology Criteria for Adverse Events version 4.0 (CTCAEv4.0). Results: Patients with advanced stage PC (n=7) or advanced peritoneal mesothelioma (n=2) received 24 doses of GL-ONC1. Adverse events were limited to grades 1-3, including transient flu-like symptoms and increased abdominal pain, resulting from treatment-induced peritonitis. No DLT was reported and the MTD was not reached. Furthermore, no signs of viral shedding were observed. Importantly, in eight out of nine study patients effective i.p. infections, in-patient replication of GL-ONC1, as well as sub­sequent oncolysis were demonstrated in cycle 1. All patients developed neutralizing activities against GL-ONC1. Conclusions: GL-ONC1 was well tolerated when administered into the peritoneal cavity of patients with advanced stage PC. Efficient tumor cell infection, in-patient virus replication as well as onco­lysis were limited to treatment cycle 1. (ClinicalTrials.gov number, NCT01443260)

https://ift.tt/2IsWM7d

Preoperative radiotherapy or chemoradiotherapy in rectal cancer – Is survival improved? An update of the “Nordic” LARC study in non-resectable cancers

The randomized "Nordic" LARC study compared preoperative long-course radiotherapy alone (RT) or with chemotherapy (CRT) in the most locally advanced/ugly rectal cancers. Despite significantly better local control in the CRT group, no overall survival benefit was seen after 10 years follow-up. The relations between local control and survival are discussed.

https://ift.tt/2Gs5z3B

Complete Response for More than 4 Years following Neoadjuvant FOLFOX and Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for a Patient with Advanced Gastric Cancer with Extensive Peritoneal Carcinomatosis

Background: Peritoneal carcinomatosis is usually a terminal disease with short median survival in patients with gastric cancer. Systemic FOLFOX is one of the most used regimens in the first-line treatment of metastatic gastric cancer. However, there is scarce evidence that cytoreductive surgery (CRS) and intraperitoneal heated chemotherapy (HIPEC) improves oncological outcomes of patients with advanced gastric cancer. Methods: Herein we present a case of a young woman with advanced gastric cancer with omental and peritoneal metastases who achieved an excellent response after 6 months of FOLFOX followed by CRS and HIPEC. Results: A 53-year-old woman was diagnosed with advanced gastric carcinoma, with extensive omental caking and several peritoneal implants measuring 2 cm at the largest diameter. The patient received mFOLFOX6 for 6 months with excellent clinical and radiographic response. She was then submitted to a D2 total gastrectomy followed by CRS and HIPEC with mitomycin. The final pathology report showed a focal adenocarcinoma in the stomach measuring 0.4 mm with no residual tumor in the peritoneum (ypT1ypN0). The patient has been well and disease free for more than 4 years. Conclusion: While still controversial, CRS followed by HIPEC may be a curative therapeutic option for highly selected patients.
Case Rep Oncol 2018;11:305–310

https://ift.tt/2L6hh7s

Malignant Transformation of Nodular Hidradenoma in the Lower Leg

Nodular hidradenoma (NH) is a benign adnexal tumor that arises from either eccrine or apocrine sweat glands. NH can originate from any cutaneous site, but the most common sites are the head and anterior surface of the trunk, with very rare cases in the extremities. Long-standing NH has been reported to undergo malignant transformation to malignant NH (MNH); however, its occurrence in the lower leg is extremely rare with only one other case reported to date. In this report, we present a rare case of MNH occurring in the lower leg which was resected with the intent to make a diagnosis. At the final follow-up after 11 months, no local recurrence or metastasis has been observed.
Case Rep Oncol 2018;11:298–304

https://ift.tt/2KzmaVv

Integrated Diagnostic Model That Incorporates Epstein-Barr Virus DNA, Imaging, and Nasal Endoscopy to Stratify Primary Tumor and Lymph Nodes in a Patient with N1 Nasopharyngeal Carcinoma: Multidisciplinary Management

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy, with a high metastatic potential. Epstein-Barr virus (EBV) infection plays a fundamental role, even if it is not well understood. The diagnosis of the disease in its early stage is infrequent. Imaging studies, positron emission tomography scans in addition to clinical examination, endoscopic examination, and biopsy provide information on the extent of the disease. The application of neoadjuvant chemotherapy followed by concomitant chemoradiation can improve the control of NPC. In March 2016, a 54-year-old male with NPC cT1 cN2 cM0, stage III (8th edition of American Joint Committee on Cancer (AJCC) staging system) underwent to a two-step treatment: induction chemotherapy by TPF regimen (docetaxel, cisplatin, 5-fluorouracil), followed by concomitant chemoradiotherapy (weekly cisplatin). The quantity of free plasma EBV-DNA can be related to the disease stage, and the detection of EBV-DNA during follow-up can be predictive of distant metastases. Especially, either plasma or serum EBV-DNA titer is estimated to reflect tumor volume. Biologically, such EBV-DNA reflects reproduced or released DNA from dead or dying tumor cells. On the other hand, EBV-specific DNA released as exosome may reflect the biological feature of the alive NPC tumor cell. The follow-up is ongoing after 21 months from a complete response.
Case Rep Oncol 2018;11:289–297

https://ift.tt/2L6gWlc

Adolescent and young adult oncology patients in France: Heterogeneity in pathways of care

Pediatric Blood &Cancer, EarlyView.


https://ift.tt/2rQUcwE

Gemcitabine/nab‐paclitaxel for pediatric relapsed/refractory sarcomas

Pediatric Blood &Cancer, EarlyView.


https://ift.tt/2k6dydX

Inclusion of dosimetric data as covariates in toxicity-related radiogenomic studies

Abstract

Purpose

This systematic review evaluates the completeness of dosimetric features and their inclusion as covariates in genetic-toxicity association studies.

Materials and methods

Original research studies associating genetic features and normal tissue complications following radiotherapy were identified from PubMed. The use of dosimetric data was determined by mining the statement of prescription dose, dose fractionation, target volume selection or arrangement and dose distribution. The consideration of the dosimetric data as covariates was based on the statement mentioned in the statistical analysis section. The significance of these covariates was extracted from the results section. Descriptive analyses were performed to determine their completeness and inclusion as covariates.

Results

A total of 174 studies were found to satisfy the inclusion criteria. Studies published ≥2010 showed increased use of dose distribution information (p = 0.07). 33% of studies did not include any dose features in the analysis of gene-toxicity associations. Only 29% included dose distribution features as covariates and reported the results. 59% of studies which included dose distribution features found significant associations to toxicity.

Conclusion

A large proportion of studies on the correlation of genetic markers with radiotherapy-related side effects considered no dosimetric parameters. Significance of dose distribution features was found in more than half of the studies including these features, emphasizing their importance. Completeness of radiation-specific clinical data may have increased in recent years which may improve gene-toxicity association studies.

https://ift.tt/2L9Kej2

Gastrointestinal cancer incidence in type 2 diabetes mellitus; results from a large population-based cohort study in the UK

Publication date: June 2018
Source:Cancer Epidemiology, Volume 54
Author(s): Roy G.P.J. de Jong, Paul J.H.L. Peeters, Andrea M. Burden, Marie L. de Bruin, Harm R. Haak, Ad A.M. Masclee, Frank de Vries, Maryska L.G. Janssen-Heijnen
BackgroundPatients with type 2 diabetes mellitus (T2DM) have been shown to have higher incidences of liver, pancreatic, and colorectal cancer compared to non-diabetic individuals. Current evidence is conflicting for other gastrointestinal (GI) cancers. Therefore, we aimed to determine incidence rates (IRs) of all GI cancers in patients with and without T2DM.MethodsA cohort study was performed using the UK Clinical Practice Research Datalink (1988-2012). A cohort of antidiabetic drug users was matched at baseline to a non-diabetic cohort, by age, sex, and practice. Crude IRs and 95% confidence intervals (95% CI) of GI cancers per 100,000 person-years were calculated stratified by age, sex, and calendar year.Results333,438 T2DM and 333,438 non-diabetic individuals were analyzed. IRs of liver (IR 26, 95% CI 24–28 vs. 8.9, 95% CI 7.7–10), pancreatic (IR 65, 95% CI 62–69 vs. 31, 95% CI 28–34), and colon cancer (IR 119, 95% CI 114–124 vs. 109, 95% CI 104–114) were significantly higher in the diabetic compared to the non-diabetic cohort, whereas the IR of oesophageal cancer was significantly lower (IR 41, 95% CI 39–44 vs. 47, 95% CI 44–51). Sex-specific IRs of colon cancer remained significantly higher in men with T2DM, and IRs of esophageal cancer remained significantly lower in women with T2DM.ConclusionIn this study, T2DM patients were shown to have higher crude IRs of liver, pancreatic and colon cancer, but not of gastric, biliary, and rectal cancer. Moreover, the lower observed IRs of oesophageal cancer in diabetic patients warrants further investigation.



https://ift.tt/2KwAttP

Marital status and survival in patients with rectal cancer: An analysis of the Surveillance, Epidemiology and End Results (SEER) database

Publication date: June 2018
Source:Cancer Epidemiology, Volume 54
Author(s): Xiangyang Wang, Weilan Cao, Chenguo Zheng, Wanle Hu, Changbao Liu
BackgroundMarital status has been validated as an independent prognostic factor for survival in several cancer types, but is controversial in rectal cancer (RC). The objective of this study was to investigate the impact of marital status on the survival outcomes of patients with RC.MethodsWe extracted data of 27,498 eligible patients diagnosed with RC between 2004 and 2009 from the Surveillance, Epidemiology and End Results (SEER) database. Patients were categorized into married, never married, divorced/separated and widowed groups.We used Chi-square tests to compare characteristics of patients with different marital status.Rectal cancer specific survival was compared using the Kaplan–Meier method,and multivariate Cox regression analyses was used to analyze the survival outcome risk factors in different marital status.ResultsThe widowed group had the highest percentage of elderly patients and women,higher proportion of adenocarcinomas, and more stage I/II in tumor stage (P < 0.05),but with a lower rate of surgery compared to the married group (76.7% VS 85.4%). Compared with the married patients, the never married (HR 1.40), widowed (HR 1.61,) and divorced/separated patients (HR 1.16) had an increased overall 5-year mortality. A further analysis showed that widowed patients had an increased overall 5-year cause-specific survival(CSS) compared with married patients at stage I(HR 1.92),stage II (HR 1.65),stage III (HR 1.73),and stage IV (HR 1.38).ConclusionOur study showed marriage was associated with better outcomes of RC patients, but unmarried RC patients, especially widowed patients,are at greater risk of cancer specific mortality.



https://ift.tt/2La8Ckj

Neoplasms-associated deaths in HIV-1 infected and non-infected patients in Bahia, Brazil

Publication date: June 2018
Source:Cancer Epidemiology, Volume 54
Author(s): Marinho Marques, Estela Luz, Mateus Leal, João Vitor Oliveira, Rejane Patrício, Eduardo Martins Netto, Carlos Brites
BackgroundHIV-infected patients are at a higher risk to develop malignancies than general population. Although AIDS-related malignancies are a common feature of late-stage disease, patients under successful antiretroviral therapy also have an increased risk for development of non-AIDS malignancies.ObjectiveTo compare the frequency and characteristics of adults HIV-infected patients and general population who died of malignancies in Bahia, Brazil from January 2000 to December 2010.MethodsNational Information System on Mortality (SIM) was searched to identify all deaths in the study period caused by malignancies in general population and in HIV patients. The frequency of malignancies in these two groups was compared. For HIV patients we also recorded the last HIV-1 RNA plasma viral load and CD4+ cells count, retrieved from oficial databases on laboratory monitoring for HIV patients.ResultsIn the study period 733,645 deaths were reported, 677,427 (92.3%) of them in individual older than 13 years. Malignancies were the cause of death in 77,174 (11.4%) of them, and 5156 (0.8%) were associated to HIV/Aids.Among deaths of HIV/Aids patients, Kaposi´s sarcoma was the most prevalent malignancy (OR: 309.7; 95% CI: 177-544), followed by non-Hodgkin lymphoma (OR: 10.1; 95% CI: 5.3-19.3), Hodgkin´s lymphoma (OR: 4.3; 95% CI: 2.2-8.4), and cranial nervous malignancies (OR: 3.3; 95% CI:1.6-7.0). HIV patients died at a significantly lower age (43.7 years), than general population (64.5 years, p < 0.0001). Patients who had a diagnosis of Aids-related malignancies had lower CD4+ cells count than those with non-AIDS relates malignancies (p = 0.04).ConclusionHIV infection is a clear risk fator for development of some malignancies, and is associated with early mortality, compared to general population. The level of CD4+ cells count predicts the type of malignancies causing death in this population.



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Effect of African-American race on cancer specific mortality differs according to clear cell vs. non-clear cell histologic subtype in metastatic renal cell carcinoma

Publication date: June 2018
Source:Cancer Epidemiology, Volume 54
Author(s): Michele Marchioni, Sabrina S. Harmouch, Sebastiano Nazzani, Marco Bandini, Felix Preisser, Zhe Tian, Anil Kapoor, Luca Cindolo, Alberto Briganti, Shahrokh F. Shariat, Luigi Schips, Pierre I. Karakiewicz
AimTo test the effect of African-American race on cancer specific mortality (CSM) in clear cell metastatic renal cell carcinoma (ccmRCC) and non-ccmRCC.Patients and methodsWithin Surveillance, Epidemiology and End Results registry (2001–2014), we identified patients with ccmRCC and non-ccmRCC. We relied on propensity score (PS) matching to reduce the effect of inherent differences between African-American vs. Caucasian patients. After PS matching that included access to cytoreductive nephrectomy (CNT), cumulative incidence, competing-risks regression (CRR) models and landmark analyses tested the effect of race on CSM.ResultsBefore PS matching, African-American patients accounted for 7.0 and 24.5% of respectively ccmRCC (N = 6742) and non-ccmRCC patients (N = 766). After PS matching, African-American patients accounted for 22.3 and 33.5% of respectively ccmRCC (N = 2050) and non-ccmRCC (N = 391) matched cohorts. In multivariable CRR models focusing on ccmRCC, higher CSM was recorded in African-Americans (HR:1.27, p < 0.001). Conversely, in non-ccmRCC, lower CSM was recorded in African-Americans (HR:0.54, p < 0.001). Landmark analyses rejected the hypothesis of immortal time bias.ConclusionAfrican-Americans experienced higher CSM in ccmRCC. Conversely, African-Americans experienced lower CSM, when diagnosed with non-ccmRCC. These differences are independent of access to CNT and warrant further study since they may have an impact on efficacy or access to systemic therapies.



https://ift.tt/2La8u4j

Alcohol intake and gastric cancer: Meta-analyses of published data versus individual participant data pooled analyses (StoP Project)

Publication date: June 2018
Source:Cancer Epidemiology, Volume 54
Author(s): Ana Ferro, Samantha Morais, Matteo Rota, Claudio Pelucchi, Paola Bertuccio, Rossella Bonzi, Carlotta Galeone, Zuo-Feng Zhang, Keitaro Matsuo, Hidemi Ito, Jinfu Hu, Kenneth C. Johnson, Guo-Pei Yu, Domenico Palli, Monica Ferraroni, Joshua Muscat, Reza Malekzadeh, Weimin Ye, Huan Song, David Zaridze, Dmitry Maximovitch, Nerea Fernández de Larrea, Manolis Kogevinas, Jesus Vioque, Eva M. Navarrete-Muñoz, Mohammadreza Pakseresht, Farhad Pourfarzi, Alicja Wolk, Nicola Orsini, Andrea Bellavia, Niclas Håkansson, Lina Mu, Roberta Pastorino, Robert C. Kurtz, Mohammad H. Derakhshan, Areti Lagiou, Pagona Lagiou, Paolo Boffetta, Stefania Boccia, Eva Negri, Carlo La Vecchia, Bárbara Peleteiro, Nuno Lunet
BackgroundIndividual participant data pooled analyses allow access to non-published data and statistical reanalyses based on more homogeneous criteria than meta-analyses based on systematic reviews. We quantified the impact of publication-related biases and heterogeneity in data analysis and presentation in summary estimates of the association between alcohol drinking and gastric cancer.MethodsWe compared estimates obtained from conventional meta-analyses, using only data available in published reports from studies that take part in the Stomach Cancer Pooling (StoP) Project, with individual participant data pooled analyses including the same studies.ResultsA total of 22 studies from the StoP Project assessed the relation between alcohol intake and gastric cancer, 19 had specific data for levels of consumption and 18 according to cancer location; published reports addressing these associations were available from 18, 5 and 5 studies, respectively. The summary odds ratios [OR, (95%CI)] estimate obtained with published data for drinkers vs. non-drinkers was 10% higher than the one obtained with individual StoP data [18 vs. 22 studies: 1.21 (1.07–1.36) vs. 1.10 (0.99–1.23)] and more heterogeneous (I²: 63.6% vs 54.4%). In general, published data yielded less precise summary estimates (standard errors up to 2.6 times higher). Funnel plot analysis suggested publication bias.ConclusionMeta-analyses of the association between alcohol drinking and gastric cancer tended to overestimate the magnitude of the effects, possibly due to publication bias. Additionally, individual participant data pooled analyses yielded more precise estimates for different levels of exposure or cancer subtypes.



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Lysophosphatidylcholine as a predictor of postoperative complications after colorectal cancer surgery

Abstract

Purpose

Lysophosphatidylcholine (LPC), which is generated from phosphatidylcholine (PC) and metabolized by autotaxin (ATX), modulates immune responses via its anti-inflammatory property. We investigated the association between LPC and postoperative complications (POCs) after colorectal cancer surgery (CRC).

Methods

The subjects of this study were 43 patients who underwent surgery for CRC. Peripheral blood samples were collected preoperatively and immediately after surgery, and on postoperative days (PODs) 1, 3, 5, and 7. Patients were divided into a No-POC group (n = 33) and a POC group (n = 10). Blood LPC, IL-6, PC, and ATX levels were measured by specific enzymatic assays or ELISA.

Results

The postoperative to preoperative LPC ratios were lowest on POD 1 in both groups. The POC group had significantly lower LPC ratios throughout the perioperative period than the No-POC group. The LPC ratios were inversely correlated with IL-6. The predictive impact of LPC ratios on POCs was demonstrated by ROC analysis (cut-off 51.2%, AUC 0.798) and multivariate analysis (OR 15.1, P = 0.01). The postoperative PC ratios decreased more after surgery in the POC group. ATX levels did not change significantly in either group.

Conclusions

Decreased postoperative LPC is associated with increased postoperative inflammatory response and POCs. The decreased PC supply to the circulation is a mechanism of the postoperative LPC decrease.

https://ift.tt/2rVs0ZR

Advances of exosome in the development of ovarian cancer and its diagnostic and therapeutic prospect

https://ift.tt/2KwuKUR

Misuse of Quality of Life Evaluation in Oncology Studies: Reification, Adaptation, and the U-Shaped Curve

Publication date: Available online 10 May 2018
Source:Practical Radiation Oncology
Author(s): Robert J. Amdur, Bhishamjit S. Chera




https://ift.tt/2GsktXs

Developing and Assessing Electronic Checklists for Safety Mindfulness, Workload and Performance

Publication date: Available online 10 May 2018
Source:Practical Radiation Oncology
Author(s): Gregg S. Tracton, Lukasz M. Mazur, Prithima Mosaly, Lawrence B. Marks, Shiva Das
PurposeTo i) propose set of innovative principles for effective design of electronic checklists to enhance safety mindfulness (a specific safety mindful mindset that offers the opportunity of operating more preemptively during routine QA tasks), and ii) discuss some of our preliminary results from testing our proposed electronic checklist with dosimetrists and physicists.Methods and materialsA multidisciplinary team designed, developed, and evaluated the utility of the electronic checklist (vs. paper-based checklist) to promote safety mindfulness. Subjective workload was measured at the end of each assessment/scenario. Performance was quantified based on discovery of purposefully embedded errors, time-to-complete the scenario, and additional concerns documented by the participants.ResultsUse of the electronic checklist was associated with decreases in time-to-scenario completion (p<0.01), increases in documentation of additional patient safety and plan quality concerns (p=0.04), but had no significant impact on recognition of purposefully embedded errors or perceptions of workload.ConclusionOur proposed principles for design of electronic checklists may improve the efficiency of QA procedures, while enhancing users' safety mindfulness. Future research is needed to better understand the utility of our proposed design principles on patient safety from a long-term use.



https://ift.tt/2rOutG8

Clinical response to radium-223 dichloride in men with metastatic castrate-resistant prostate cancer

Publication date: Available online 16 May 2018
Source:Practical Radiation Oncology
Author(s): Isabella Zhang, Philip Gilbo, Nina Kohn, Brett Cox
Purpose/ObjectiveRadium-223 prolongs survival and decreases symptomatic skeletal events in men with metastatic castrate-resistant prostate cancer and is indicated in patients with painful bone metastases. However, pain responses are rarely reported and often asked about by patients. Further, patients and their physicians are concerned about a lack of pain response portending a poor treatment response and may be inclined to change systemic therapies before completing 6cycles. We evaluated the likelihood and time course of pain response, potential predictors of response, and its prognostic value in patients receiving radium-223.Materials and MethodsWe reviewed the charts of patients who received radium-223 in our department. All patients were planned for 6cycles with a prescribed dose of 50–55kBq/kg at each administration. Pain scores, subjective response to pain, analgesic use, treatment toxicities, and laboratory values were recorded at each visit. Symptomatic skeletal events and survival were also recorded.Results48 patients received at least one cycle of radium-223 and 27 (56%) received all 6 planned cycles. Median survival from first treatment was 16.0months (95% CI 8.9 to 19.2months). 33% experienced at least one symptomatic skeletal event during or after treatment. 62.5% of men reported a decrease in pain from pre-treatment baseline. Of men with improved pain, 96% experienced an improvement before the third cycle. Pain relief was not associated with a decrease in ALK-P or PSA or improved survival.ConclusionsApproximately two-thirds of patients who undergo treatment with radium-223 will experience an improvement in pain and, if it occurs, it will most likely occur within the first two cycles. Patients should be counseled about this timeline and, if pain improvement isn't achieved, palliative radiation and oral analgesic readjustment should be considered. Pain response is not associated with survival and should not be used to evaluate the effectiveness of treatment.



https://ift.tt/2Gqsn3q

Prospective analysis of different combined regimens of stereotactic body radiation therapy and chemotherapy for locally advanced pancreatic cancer

Cancer Medicine, EarlyView.


https://ift.tt/2rNywlb

Sleep and mood during hospitalization for high‐dose chemotherapy and hematopoietic rescue in pediatric medulloblastoma

Psycho-Oncology, EarlyView.


https://ift.tt/2IPJsco

Falling through the cracks. A thematic evaluation of unmet needs of adult survivors of childhood cancers

Psycho-Oncology, EarlyView.


https://ift.tt/2Itgiwz

Fear of recurrence among older breast, ovarian, endometrial, and colorectal cancer survivors: Findings from the WHI LILAC study

Psycho-Oncology, EarlyView.


https://ift.tt/2rP6G8V

Psychosexual development and satisfaction with timing of developmental milestones among adult survivors of childhood cancer

Psycho-Oncology, EarlyView.


https://ift.tt/2ItgdJh

A cross‐sectional study of agreement between the Hospital Anxiety and Depression Scale and patient‐ and radiation oncologist–reported single‐item assessment of depression and anxiety

Psycho-Oncology, EarlyView.


https://ift.tt/2IJAoGb

Association between information provision and supportive care needs among ovarian cancer survivors: A cross‐sectional study from the PROFILES registry

Psycho-Oncology, EarlyView.


https://ift.tt/2Itgax5

Peritoneal carcinomatosis index as a predictor of diaphragmatic involvement in stage III and IV ovarian cancer

https://ift.tt/2L66UjY

Identifying miRNA and gene modules of colon cancer associated with pathological stage by weighted gene co-expression network analysis

https://ift.tt/2Kwr31u

5-Azacytidine treatment induces demethylation of DAPK1 and MGMT genes and inhibits growth in canine mammary gland tumor cells

https://ift.tt/2L7hWpi

NDRG3 facilitates colorectal cancer metastasis through activating Src phosphorylation

https://ift.tt/2KzH4DN

Early versus late prophylactic cranial irradiation in patients with extensive small cell lung cancer

Abstract

Objective

Previous studies demonstrated that prophylactic cranial irradiation (PCI) significantly reduced the incidence of brain metastases in patients with extensive disease small cell lung cancer (ED-SCLC). However, the appropriate timing for PCI in treating ED-SCLC is still unclear. This study aimed to compare the effect and safety of early versus late PCI.

Methods

Between November 2011 and July 2016, 103 patients with ED-SCLC were reviewed, receiving appropriate imaging tests to exclude brain metastases prior to cranial irradiation. Of these 103 patients, early PCI was performed in 47 patients and the other 56 patients received late PCI. The primary endpoint was the incidence of brain metastases. The progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were also assessed.

Results

Early PCI significantly lowered the risk of brain metastases, as compared to late PCI (p = 0.024). Additionally, multivariate analyses demonstrated that early PCI was a favorable independent predictor of the incidence of brain metastases. The PFS and OS of patients in the early and late PCI groups were comparable (PFS: 8.4 months vs. 7.5 months, p = 0.234; OS: 16.1 months vs. 15.2 months, p = 0.753). The AEs were generally acceptable in both groups.

Conclusion

To reduce the incidence of brain metastases, early PCI is more effective than late PCI for ED-SCLC patients.

https://ift.tt/2k68JBo

Tumor volume as a prognostic marker in p16-positive and p16-negative oropharyngeal cancer patients treated with definitive intensity-modulated radiotherapy

Abstract

Purpose

To investigate the impact of primary gross tumor volume (pGTV) and nodal gross tumor volume (nGTV) in oropharyngeal squamous cell carcinoma (OPSCC) and the difference in their role between human papillomavirus (HPV)-positive and HPV-negative patients.

Methods

The patient cohort consists of 91 OPSCC patients treated with definitive radiochemotherapy or radiotherapy using intensity-modulated radiotherapy (IMRT). All patients had a minimum follow-up of 31 months. Volume measurements were made from computer tomography (CT) scans and HPV status was assessed by p16 immunohistochemistry. The end points were as follows: overall survival (OS), disease-free survival (DFS) and locoregional control (LRC).

Results

pGTV was a significant independent prognostic factor for overall survival (OS; p = 0.020) in p16-negative patients. nGTV of p16-negative tumors had significant prognostic value in all end points in multivariate analyses. High-stage (III–IVc) p16-negative tumors were only associated with significantly poorer OS (p = 0.046) but not with poorer LRC or DFS when compared with the low-stage (I–II) tumors. nGTV of p16-positive tumors was an independent prognostic factor for DFS (p = 0.005) and LRC (p = 0.007) in multivariate analyses.

Conclusion

pGTV may serve as an independent prognostic factor in p16-negative patients and nGTV may serve as an independent prognostic factor both in p16-positive and p16-negative patients treated with radiochemotherapy or radiotherapy using IMRT. Tumor volume may have an impact on selecting patients for de-escalation protocols in the future, both in p16-positive and p16-negative patients.

https://ift.tt/2KsSxoE

The battle over indoor tanning heats up

Cancer Cytopathology, Volume 126, Issue 5, Page 297-298, May 2018.


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Issue Information

Cancer Cytopathology, Volume 126, Issue 5, Page 291-296, May 2018.


https://ift.tt/2rQPDCJ

Clinical resistance associated with a novel MAP2K1 mutation in a patient with Langerhans cell histiocytosis

Pediatric Blood &Cancer, EarlyView.


https://ift.tt/2rOXstj

Is chronological age really not a contraindication to gastrectomy for very elderly patients?

https://ift.tt/2GoZCEw

Next-Gen Therapeutics for Skin Cancer: Nutraceuticals.

Related Articles

Next-Gen Therapeutics for Skin Cancer: Nutraceuticals.

Nutr Cancer. 2018 May 15;:1-13

Authors: Sreedhar A, Li J, Zhao Y

Abstract
Growing modernization and lifestyle changes with limited physical activity have impacted diet and health, leading to an increased cancer mortality rate worldwide. As a result, there is a greater need than before to develop safe and novel anticancer drugs. Current treatment options such as chemotherapy, radiotherapy and surgery, induce unintended side effects, compromising patient's quality of life, and physical well-being. Therefore, there has been an increased global interest in the use of dietary supplements and traditional herbal medicines for treatment of cancer. Recently, nutraceuticals or "natural" substances isolated from food have attracted considerable attention in the cancer field. Emerging research suggests that nutraceuticals may indeed prevent and protect against cancer. The intent of this article is to review some of the current spice-derived nutraceuticals in the treatment of melanoma and skin cancer.

PMID: 29764209 [PubMed - as supplied by publisher]

https://ift.tt/2IvHJWc

Primary tumor sidedness is an independent prognostic marker for survival in metastatic colorectal cancer: Results from a large retrospective cohort with mutational analysis

Cancer Medicine, EarlyView.


https://ift.tt/2Iryvuc

Serum SP70 is a sensitive predictor of chemotherapy response in patients with advanced nonsmall cell lung cancer

Cancer Medicine, EarlyView.


https://ift.tt/2rNIjZc

Prognosis of patients with hepatocellular carcinoma treated with sorafenib: a comparison of five models in a large Canadian database

Cancer Medicine, EarlyView.


https://ift.tt/2It3rKP

Genomic characterization of individuals presenting extreme phenotypes of high and low risk to develop tobacco‐induced lung cancer

Cancer Medicine, EarlyView.


https://ift.tt/2rMD7F8

Rituximab maintenance therapy of follicular lymphoma in clinical practice

Cancer Medicine, EarlyView.


https://ift.tt/2IsLJHh

The combination of a sphingosine kinase 2 inhibitor (ABC294640) and a Bcl‐2 inhibitor (ABT‐199) displays synergistic anti‐myeloma effects in myeloma cells without a t(11;14) translocation

Cancer Medicine, EarlyView.


https://ift.tt/2IMJSQU

FM19G11 inhibits O6‐methylguanine DNA‐methyltransferase expression under both hypoxic and normoxic conditions

Cancer Medicine, EarlyView.


https://ift.tt/2IriaWl

Endometrial cancer—how many patients could benefit from sentinel lymph node dissection?

Abstract

Background

Sentinel lymph node dissection (SLND) may reduce morbidity in patients with endometrial cancer. The objective of this study is to estimate how many systematic lymph node dissections (LND) can be spared with an implementation of a SLN-procedure.

Methods

Retrospective, single-center study, SLND according to NCCN-Guidelines.

Results

In 109 patients of 154 consecutive patients, SLND was performed. The detection rate was 61% on both sides and 86% on at least one side. Classification of uterine risk factors is as follows: low risk 53, intermediate risk 25, high-intermediate risk 13, and high-risk 18. Stage IIIC: 0, 3, 7, 11, respectively. Under the assumption that 56 patients with "higher than low risk" factors would be treated by systematic LND, we spared 26 pelvic and paraaortic LND. After failures of SLN detection, unilateral pelvic LND was performed in 15 patients. Patients with "higher than low risk" factors and node-negative SLN are candidates for a randomized study to prove safety and efficacy. Only every third patient in our study met these criteria.

Conclusions

In a cohort of patients with "higher than low risk" endometrial cancer, the implementation of SLND nearly divided the number of radical lymph node dissections in half. Further studies are required to define the best modalities for SLND.

https://ift.tt/2k3nqoH

Increased centrosome number in BRCA‐related breast cancer specimens determined by immunofluorescence analysis

Cancer Science, EarlyView.


https://ift.tt/2ImR9HP

The burden of prostate cancer in Trinidad and Tobago: one of the highest mortality rates in the world

Abstract

Purpose

In Trinidad and Tobago (TT), prostate cancer (CaP) is the most commonly diagnosed malignancy and the leading cause of cancer deaths among men. TT currently has one of the highest CaP mortality rates in the world.

Methods

6,064 incident and 3,704 mortality cases of CaP occurring in TT from January 1995 to 31 December 2009 reported to the Dr. Elizabeth Quamina Cancer population-based cancer registry for TT, were analyzed to examine CaP survival, incidence, and mortality rates and trends by ancestry and geography.

Results

The age-standardized CaP incidence and mortality rates (per 100,000) based on the 1960 world-standardized in 2009 were 64.2 and 47.1 per 100,000. The mortality rate in TT increased between 1995 (37.9 per 100,000) and 2009 (79.4 per 100,000), while the rate in the US decreased from 37.3 per 100,000 to 22.1 per 100,000 over the same period. Fewer African ancestry patients received treatment relative to those of Indian and mixed ancestry (45.7%, 60.3%, and 60.9%, respectively).

Conclusions

Notwithstanding the limitations surrounding data quality, our findings highlight the increasing burden of CaP in TT and the need for improved surveillance and standard of care. Our findings highlight the need for optimized models to project cancer rates in developing countries like TT. This study also provides the rationale for targeted screening and optimized treatment for CaP to ameliorate the rates we report.

https://ift.tt/2rKnjSm