PrecisionPanc, Personalised treament for pancreatic cancer, Wellcome Trust

Impact ◽  
2018 ◽  
Vol 2018 (3) ◽  
pp. 6-10
Author(s):  
Andrew Biankin
Keyword(s):  
Pancreatic Cancer ◽  
Translational Research ◽  
Cancer Patients ◽  
Patient Outcomes ◽  
Therapeutic Approach ◽  
Research Study ◽  
Therapeutic Option ◽  
Reliable Information ◽  
Wide Range ◽  
Experienced Team

Simply put, we want to help pancreatic cancer patients, and their doctors, to find and understand accurate and reliable information about that specific patient's cancer that could help them to decide what the most suitable type of treatment is. Our latest research study, which was co-led by Professor Andrew Biankin and was recently published in Nature, demonstrates that pancreatic cancer can be classified into four subtypes - each of which may require a different therapeutic approach. This shows that understanding the molecular differences between the pancreatic cancer in one patient and another is vital when considering what the most suitable therapeutic option is. We also carry out a wide range of basic and translational research studies to help us generally improve our understanding of how pancreatic cancer behaves and grows. Over the coming weeks we will post more details of our projects so you can follow our activities and understand how we are working actively to fight pancreatic cancer. Currently, we are implementing our strategies and thoroughly testing our pipelines and processes to allow us to help patients. Our experienced team of clinicians, researchers, bioinformaticians and lab staff work tirelessly with one thing in mind: improving patient outcomes.

Comparative circulating tumor DNA levels for KRAS mutations in patients with nonresectable pancreatic cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 288-288 ◽  
Author(s):  
Julia S. Johansen ◽  
Cecile Rose T. Vibat ◽  
Dan Calatayud ◽  
Benny Vittrup Jensen ◽  
Jane Preuss Hasselby ◽  
...  
Keyword(s):  
Patient Outcome ◽  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Kras Mutation ◽  
Circulating Tumor Dna ◽  
Resectable Pancreatic Cancer ◽  
Kras Mutations ◽  
Study Objective ◽  
Wide Range ◽  
Tumor Dna

288 Background: Non-resectable pancreatic cancer patients have a wide range of median time for overall survival (OS). Currently there is a lack of diagnostic tools to predict patient outcome at diagnosis. KRAS mutations are present in the vast majority of pancreatic tumors. The study objective was to determine if quantitative baseline and longitudinal monitoring of KRAS mutations from plasma circulating tumor DNA (ctDNA) could be used to stratify patients for predicting outcome. Methods: Plasma was prospectively collected from the Danish BIOPAC study for non-resectable pancreatic cancer patients undergoing treatment with gemcitabine or FOLFIRINOX. Feasibility of monitoring ctDNA KRAS mutations was assessed in 10 patients with long OS (median 493 days; range 360-1031) and 10 patients with short OS (median 66 days; range 21-136). KRAS G12A/C/D/R/S/V, and G13D mutations were PCR enriched, sequenced by massively parallel deep sequencing, quantitated and standardized by reporting number of copies detected per 105 genome equivalents (GE). Results: In a pilot study of 20 patients, all 18 patients with evaluable DNA had detectable KRAS mutations. Of 18 patients, 12 had baseline plus longitudinal time points (7 short, 5 long OS). Mutant KRAS copies were higher for short OS (median=994; range 0-34305 copies/105 GE) vs. with long OS (median 196; range, 34-278 copies/105 GE). Longitudinally, KRAS mutation levels remained mostly low with long OS (last time point median 204; range 8-873 copies/105 GE) vs. short OS where levels increased or remained high (median 2363; range 71-47919 copies/105 GE). Identical KRAS mutations were consistently detected for a given patient with short OS. However, long OS patients had variable KRAS mutations in longitudinal analysis. Conclusions: High levels of ctDNA KRAS mutations at diagnosis and post-treatment elevation of KRAS mutations were more associated with short OS. Different levels of KRAS mutation at diagnosis may predict patient outcome and could reflect distinct underlying tumor biology. Expansion of this prospective-retrospective biomarker cohort will be reported.

Opportunities for improving outcomes in pancreatic cancer patients: Characterizing the unresected “resectable” population.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 274-274
Author(s):  
Jonathan Kish ◽  
Bruce A. Feinberg ◽  
Tracy Maida ◽  
Craig Biggs ◽  
Urvi Mujumdar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Surgical Resection ◽  
Metastatic Disease ◽  
Therapeutic Option ◽  
Cancer Outcomes ◽  
Real World Data ◽  
Curative Intent ◽  
Claims Database ◽  
Mean Time

274 Background: Resection is the only curative intent therapeutic option for pancreatic adenocarcinoma (PA). Recent studies suggest adjuvant chemo can significantly improve overall survival (OS). Patients who may be eligible for, but do not receive, a resection (“resectable”) may represent an opportunity to improve pancreatic cancer outcomes. This research sought to characterize this population using real-world data. Methods: Individuals with pancreatic cancer (ICD-9=157.x, excluding 157.4) diagnosed between 03/2012-06/2015 were selected from the Inovalon More2 claims database. Resection was defined as the presence of any of the following codes on any claim following diagnosis: CPT=48140, 48146, 48150, 48152-5. A diagnosis of metastatic disease was said to occur if any of the following ICD-9 CM codes were present on a claim: 196.0-196.3, 196.5-196.6, 197.0-197.8, and 198.0-198.8. Patients were deemed “resectable” if there was no claim for surgical resection and if their claim for metastatic disease was post-initiation of chemotherapy. Results: Of 7,159 patients identified with PA, 85.8% (n=6,145) were unresected, 40.8% (n=2,924) had received chemotherapy which included 54.4% (n=552) of resected patients and 38.6% (n=2,372) of non-resected patients. Of unresected patients receiving chemotherapy, 27.4% had no record of a metastatic diagnosis, 51.9% had a metastatic diagnosis prior to the start of chemotherapy (mean time metastatic diagnosis = 0.4 months) and 20.7% had a metastatic diagnosis after the initiation of chemotherapy (mean time metastatic diagnosis = 4.8 months). Overall, 18.5% (n=1139) of non-resected patients were classified as unresected “resectable”. Conclusions: The vast majority (85.8%) of pancreatic cancer patients did not undergo a surgical resection. We estimate as many as 18.5% of non-resected patients may be unresected “resectable” given 4.8 months between diagnosis, chemotherapy start and documentation of metastases. As surgical resection is the only curative intent therapeutic option, and prolongs survival even in those not cured, identifying patients who may be eligible for resection is critical to improving pancreatic cancer outcomes.

scholarly journals Perturbation of the gut microbiota by antibiotics results in accelerated breast tumour growth and metabolic dysregulation

2019 ◽  
Author(s):  
Benjamin M Kirkup ◽  
Alastair McKee ◽  
Kate A Makin ◽  
Jack Paveley ◽  
Shabhonam Caim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gut Microbiota ◽  
Cancer Patients ◽  
Patient Outcomes ◽  
Tumour Growth ◽  
Immune Cell ◽  
Breast Tumour ◽  
Antibiotic Administration ◽  
Breast Cancer Patients ◽  
Wide Range

AbstractBackgroundBreast cancer is the second most prevalent cancer worldwide with around 1.7 million new cases diagnosed every year. Whilst prognosis is generally favourable in early stages, this worsens significantly in advanced disease. Therefore, it is pertinent to focus on mitigating factors that may slow growth or progression. Recently, the gut microbiome has been implicated in a wide-range of roles in tumour biology. Through modulation of immunity, the gut microbiota can improve the efficacy of several immunotherapies. However, despite the prevalence of breast cancer, there is still a lack of microbiota studies in this field, including exploring the influence of external microbiome-modulating factors such as antibiotics. We describe herein how disruption of the gut microbiota via antibiotics may be detrimental to patient outcomes through acceleration of tumour growth.ResultsSupplementing animals with a cocktail of antibiotics leads to gut microbiota alterations and is accompanied by significant acceleration of tumour growth. Surprisingly, and distinct from previous microbiome-tumour studies, the mechanism driving these effects do not appear to be due to gross immunological changes. Analysis of intratumoural immune cell populations and cytokine production are not affected by antibiotic administration. Through global tumour transcriptomics, we have uncovered dysregulated gene expression networks relating to protein and lipid metabolism that are correlated with accelerated tumour growth. Fecal metabolomics revealed a reduction of the microbial-derived short-chain fatty acid butyrate that may contribute to accelerated tumour growth. Finally, through use of a routinely administered antibiotic in breast cancer patients, Cephalexin, we have shown that tumour growth is also significantly affected. Metataxanomic sequencing and analysis highlighted significant antibiotic-associated reductions in the butyrate producing generaOdoribacterandAnaeotruncus, and increased abundance ofBacteroides.ConclusionsOur data indicate that perturbation of the microbiota by antibiotics may have negative impacts on breast cancer patient outcomes. This is of importance as antibiotics are regularly prescribed to breast cancer patients undergoing mastectomy or breast reconstruction. We have also shown that the metabolic impact of disruption to the microbiome should be considered alongside the potent immunological effects. We believe our work lays the foundation for improving the use of antibiotics in patients, and with further investigation could potentially inform clinical practice.

FEASIBILITY OF ORAL AND DUODENAL MICROBIOTA ANALYSIS OF PANCREATIC CANCER PATIENTS AND CONTROLS

2020 ◽  
Author(s):  
L Archibugi ◽  
MC Petrone ◽  
G Rossi ◽  
A Mariani ◽  
SGG Testoni ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Microbiota Analysis

Selecting a PRO-CTCAE based subset for patient reported symptom monitoring during lung cancer treatment (Preprint)

2020 ◽  
Author(s):  
Evalien Veldhuijzen ◽  
Iris Walraven ◽  
Jose Belderbos
Keyword(s):  
Lung Cancer ◽  
Clinical Practice ◽  
Cancer Patients ◽  
Treatment Modalities ◽  
European Organization ◽  
Specific Patient ◽  
Symptom Monitoring ◽  
Lung Cancer Patients ◽  
Wide Range ◽  
Patient Reported

BACKGROUND The Patient Reported Outcomes Version of the Common Terminology Criteria of Adverse Events (PRO-CTCAE) item library covers a wide range of symptoms relevant for oncology care. To enable implementation of PRO-CTCAE-based symptom monitoring in clinical practice, there is a need to select a subset of items relevant for specific patient populations. OBJECTIVE The aim of this study was to develop a PRO-CTCAE subset relevant for patients with lung cancer. METHODS The PRO-CTCAE-based subset for lung cancer patients was generated using a mixed methods approach based on the European Organization for Research and Treatment of Cancer (EORTC) guidelines for developing questionnaires, consisting of a literature review and semi-structured interviews with both lung cancer patients and health care practitioners (HCPs). Both patients and HCPs were queried on the relevance and impact of all PRO-CTCAE items. Results were summarized and, after a final round of expert review, a selection of clinically relevant items for lung cancer patients was made. RESULTS A heterogeneous group of lung cancer patients (n=25) from different treatment modalities and HCPs (n=22) participated in the study. A final list of eight relevant PRO-CTCAE items was created: decreased appetite, cough, shortness of breath, fatigue, constipation, nausea, sadness, and pain (general). CONCLUSIONS Based on literature and both professional and patient input, a subset of PRO-CTCAE items has been identified for use in lung cancer patients in clinical practice. Future work is needed to confirm the validity and effectiveness of this PRO-CTCAE lung cancer subset internationally, and in the real-world clinical practice setting.

scholarly journals Circulating cytokine levels as biomarkers for response to FOLFIRINOX chemotherapy in pancreatic cancer patients

HPB ◽  
2021 ◽  
Vol 23 ◽  
pp. S233-S234
Author(s):  
F. van der Sijde ◽  
W. Dik ◽  
D. Mustafa ◽  
E. Vietsch ◽  
C. van Eijck
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Cytokine Levels

scholarly journals P31-7 Clinical outcomes of cerebral infarction associated with Trousseau’s syndrome in advanced pancreatic cancer patients

2021 ◽  
Vol 32 ◽  
pp. S350
Author(s):  
Tomoyo Oguri ◽  
Hiroyuki Takeda ◽  
Kumiko Umemoto ◽  
Ayako Doi ◽  
Hiroyuki Arai ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cerebral Infarction ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Advanced Pancreatic Cancer ◽  
Trousseau’S Syndrome

scholarly journals Cochlear Implant Research and Development in the Twenty-first Century: A Critical Update

2021 ◽  
Vol 22 (5) ◽  
pp. 481-508
Author(s):  
Robert P. Carlyon ◽  
Tobias Goehring
Keyword(s):  
Research And Development ◽  
Patient Outcomes ◽  
Speech Processing ◽  
Turn Of The Century ◽  
First Century ◽  
Directional Microphones ◽  
Wide Range ◽  
The Subject ◽  
Processing Algorithms ◽  
Improve Patient

AbstractCochlear implants (CIs) are the world’s most successful sensory prosthesis and have been the subject of intense research and development in recent decades. We critically review the progress in CI research, and its success in improving patient outcomes, from the turn of the century to the present day. The review focuses on the processing, stimulation, and audiological methods that have been used to try to improve speech perception by human CI listeners, and on fundamental new insights in the response of the auditory system to electrical stimulation. The introduction of directional microphones and of new noise reduction and pre-processing algorithms has produced robust and sometimes substantial improvements. Novel speech-processing algorithms, the use of current-focusing methods, and individualised (patient-by-patient) deactivation of subsets of electrodes have produced more modest improvements. We argue that incremental advances have and will continue to be made, that collectively these may substantially improve patient outcomes, but that the modest size of each individual advance will require greater attention to experimental design and power. We also briefly discuss the potential and limitations of promising technologies that are currently being developed in animal models, and suggest strategies for researchers to collectively maximise the potential of CIs to improve hearing in a wide range of listening situations.

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