Clinical impact of neoadjuvant treatment in resectable pancreatic cancer: a systematic review and meta-analysis protocol

Lee, J-C. et al. BMJ Open. 2016;6:e010491
Image source: Wellcome Photo Library // CC BY-NC-ND

Image of photomicrograph showing adenocarcinoma of the pancreas.

Introduction: Although the only curative strategy for pancreatic cancer is surgical resection, up to 85% of patients relapse after surgery. The efficacy of neoadjuvant treatment in resectable pancreatic cancer (RPC) remains unclear and there is no systematic review focusing fully on this issue. Recently, two prospective trials of neoadjuvant treatment in RPC were terminated early because of slow recruiting and existing randomised controlled trials (RCTs) have too small sample sizes. Therefore, to overcome probable biases, it would be more reasonable to include both RCTs and non-randomised studies (NRSs) with selected criteria. This review aims to investigate the effect of neoadjuvant chemotherapy (CTx) and chemoradiation therapy (CRT) in RPC using RCTs and specific NRSs.

Method and analysis: This systematic review will include conventional RCTs as group I, and quasi-randomised controlled trials, non-randomised controlled trials and prospective cohort studies as group II. Two groups will be assessed and analysed separately. Comprehensive literature search will use Medline, Embase, Cochrane library and Scopus databases. Additionally, we will search references from relevant studies and abstracts from major conferences. Two authors will independently identify, screen, include studies, extract data and assess the risk of bias. Discrepancies will be resolved by consensus with another author. An independent methodologist will categorise and assess NRSs to minimise heterogeneity. In each study group, meta-analysis will be conducted using a random-effect model and statistical heterogeneity will be evaluated using I2-statistics. Publication bias will be visualised with contour-enhanced funnel plots and analysed with Egger’s test. In group I, cumulative meta-analysis will be considered because the CTx regimen and CRT protocol have changed. The quality of evidence will be summarised using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

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Prostate cancer drug approved for routine use before chemotherapy

CRUK. 21 March 2016
Image Source: Anne Weston, LRI, CRUK – Wellcome Images // CC BY-NC-ND 4.0

Image shows false-coloured scanning electron micrograph of a single prostate cancer cell grown in culture

The National Institute for Health and Care Excellence (NICE) has approvedthe drug abiraterone for men with advanced prostate cancer, who have not yet had chemotherapy.  The drug – developed by UK scientists – can delay the disease’s progression, help to prolong life, and provide a better quality of life with less fatigue and pain. It has been available across the UK for men after chemotherapy since 2012.

Today’s decision – a reversal of NICE’s previous ruling – brings England and Wales in line with Scotland, which approved(link is external) the drug for men pre-chemotherapy last year. NICE was able to rule favourably after the drug’s manufacturers, Janssen, provided new data showing the drug’s cost-effectiveness, and agreed a discount price for the NHS.

Under the discount, the NHS will pay for the first 10 months of treatment. For people who remain on treatment for more than 10 months, Janssen will cover the drug’s cost from the 11th month until the end of treatment.

Until now, the drug was only available to patients in England before chemotherapy through the Cancer Drugs Fund (CDF), and was the second most requested medicine on the fund. Today’s approval means that drug can now also been removed from the Fund – which is the process of being reformed – and paid for routinely by the NHS.

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Palliative chemotherapy: oxymoron or misunderstanding?

Oncologists routinely prescribe chemotherapy for patients with advanced cancer. This practice is sometimes misunderstood by palliative care clinicians, yet data clearly show that chemotherapy can be a powerful palliative intervention when applied appropriately. Clarity regarding the term “palliative chemotherapy” is needed: it is chemotherapy given in the non-curative setting to optimize symptom control, improve quality of life, and sometimes to improve survival. Unfortunately, oncologists lack adequate tools to predict which patients will benefit. In a study recently published in BMC Palliative Care, Creutzfeldt et al. presented an innovative approach to advancing the science in this area: using patient reported outcomes to predict responses to palliative chemotherapy.

With further research, investigators may be able to develop predictive models for use at the bedside to inform clinical decision-making about the risks and benefits of treatment. In the meantime, oncologists and palliative care clinicians must work together to reduce the use of “end-of-life chemotherapy”—chemotherapy given close to death, which does not improve longevity or symptom control—while optimizing the use of chemotherapy that has true palliative benefits for patients.

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New treatment for Chronic Lymphatic Leukemia could replace chemotherapy

Medical University of Vienna. ScienceDaily, 15 March 2016.
Image source: Wellcome Photo Library // CC BY-NC-ND 4.0

Image shows photomicrograph of bone marrow acid phosphatase in acute T-cell lymphocytic leukaemia

Studies conducted at the Comprehensive Cancer Center at MedUni Vienna and Vienna General Hospital show that the drugs ibrutinib and idelalisib used in the targeted treatment of chronic lymphatic leukemia can significantly prolong the survival time of high-risk patients. The average survival time of these patients is between one and two years when they receive standard treatment, whereas 80% of patients receiving the new treatment were still alive after two years. These results give us reason to hope that, in future, these two drugs could not only replace chemotherapy but even stem cell transplantation.

Both drugs are so-called “small molecules” and belong to the class of substances known as kinase inhibitors. They are used in targeted cancer treatment, where they interrupt the signalling pathways of the cancer cells. Both substances inhibit cell growth and idelalisib additionally affects the cells’ ability to metastasize. Over the course of the last two years, they have been separately tested in studies at MedUni Vienna and are now routinely available to patients.

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Human papillomavirus detection in a “Digital” age

Justin A. Bishop and Patrick K. Ha. Cancer.  Published online: 17 March 2016
Image source: Wellcome Images // CC BY-NC-ND 4.0 

Image shows a high power view of squamous mucosa of the cervix, with mild abnormalities related to human papillomavirus (HPV) infection.

It is increasingly important to identify the presence of human papillomavirus (HPV) in patients with oropharyngeal squamous cell carcinoma, because HPV status is now useful for clinical trial stratification, prognostic determination, diagnosis in patients with neck masses, and identification of the primary tumor site. Therefore, it is important that the technique used for identification be feasible, accurate, reproducible, and cost effective. The authors summarize these aspects of HPV detection and the use of newer digital polymerase chain reaction technology for this purpose.

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Cancer Drugs Fund

Faster access to effective cancer treatments through new Cancer Drugs Fund

New arrangements for the Cancer Drugs Fund have been approved by NICE’s Board. NICE will now be able to make decisions on cancer drugs faster than ever before.

For the first time NICE will issue draft guidance on new cancer drugs or significant new licence indications before they have received marketing approval in the UK. Any drug that receives a positive draft recommendation would then be funded from the point of licence.

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Risk of second cancers in the era of modern radiation therapy: does the risk/benefit analysis overcome theoretical models?

Chargari, C. et al. Cancer and Metastasis Reviews. pp 1-12. First online: 12 March 2016

N0037758 Radiographer with a Stereotactic Body Radiation Therapy unit
Image source: David Bishop, Royal Free Hospital London – Wellcome Images

In the era of modern radiation therapy, the compromise between the reductions in deterministic radiation-induced toxicities through highly conformal devices may be impacting the stochastic risk of second malignancies.

We reviewed the clinical literature and evolving theoretical models evaluating the impact of intensity-modulated radiation therapy (IMRT) on the risk of second cancers, as a consequence of the increase in volumes of normal tissues receiving low doses.

The risk increase (if any) is not as high as theoretical models have predicted in adults. Moreover, the increase in out-of-field radiation doses with IMRT could be counterbalanced by the decrease in volumes receiving high doses. Clinical studies with short follow-up have not corroborated the hypothesis that IMRT would drastically increase the incidence of second cancers. In children, the risk of radiation-induced carcinogenesis increases from low doses and consequently the relative risk of second cancers after IMRT could be higher than in adults, justifying current developments of proton therapy with priority given to this population.

Although only longer follow-up will allow a true assessment of the real impact of these modern techniques on radiation-induced carcinogenesis, a comprehensive risk-adapted strategy will help minimize the probability of second cancers.

Read the abstract here