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.

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Urgent surgery after emergency presentation for colorectal cancer has no impact on overall and disease-free survival:

Weixler, B. et al. BMC Cancer. 2016 16:208

B0009747 Venous invasion of colorectal cancer, modified histology
Image source: Richard Kirsch & Raw ‘n’ Wild – Wellcome Images

Image shows histologic section of a surgically removed colon cancer (stage II adenocarcinoma) stained with Movat’s pentachrome stain and subsequently digitally enhanced.

Background: It remains a matter of debate whether colorectal cancer resection in an emergency setting negatively impacts on survival. Our objective was therefore to assess the impact of urgent versus elective operation on overall and disease-free survival in patients undergoing resection for colorectal cancer by using propensity score adjusted analysis.

Methods: In a single-center study patients operated for colorectal cancer between 1989 and 2013 were identified from a prospectively maintained database. Median follow-up was 44 months. Patients with neoadjuvant treatment were excluded. The impact of urgent operation on overall and disease-free survival was assessed using both Cox regression and propensity score analyses.

Results: Of 747 patients with colorectal cancer, 84 (11 %) had urgent and 663 elective cancer resection. The propensity score revealed strongly biased patient characteristics (0.22 ± 0.16 vs. 0.10 ± 0.09; P < 0.001). In unadjusted analysis urgent operation was associated with a 35 % increased risk of overall mortality (hazard ratio(HR) of death = 1.35, 95 % confidence interval(CI):1.02–1.78, P = 0.045). In risk-adjusted Cox regression analysis urgent operation was not associated with poor overall (HR = 1.08, 95 %CI:0.79–1.48; P = 0.629) or disease-free survival (HR = 1.02, 95 %CI:0.76–1.38; P = 0.877). Similarly in propensity score analysis urgent operation did not influence overall (HR = 0.98, 95 % CI:0.74–1.29), P = 0.872) and disease-free survival (HR = 0.89, 95 %CI:0.68 to 1.16, P = 0.387).

Conclusions: This study provides evidence that worse oncologic outcomes after urgent operation for colorectal cancer are caused by clinical circumstances and not due to the urgent operation itself. Urgent operation is not a risk factor for colorectal cancer resection.

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Quality of life not notably better for women choosing double mastectomy

Hwang, E. S. et al. ‘Patient-Reported Outcomes After Choice for Contralateral Prophylactic Mastectomy’. Journal of Clinical Oncology. Published online: March 7, 2016.

Purpose: The rate of contralateral prophylactic mastectomies (CPMs) continues to rise, although there is little evidence to support improvement in quality of life (QOL) with CPM. We sought to ascertain whether patient-reported outcomes and, more specifically, QOL differed according to receipt of CPM.

Methods: Volunteers recruited from the Army of Women with a history of breast cancer surgery took an electronically administered survey, which included the BREAST-Q, a well-validated breast surgery outcomes patient-reporting tool, and demographic and treatment-related questions. Descriptive statistics, hypothesis testing, and regression analysis were used to evaluate the association of CPM with four BREAST-Q QOL domains.

Results: A total of 7,619 women completed questionnaires; of those eligible, 3,977 had a mastectomy and 1,598 reported receipt of CPM. Women undergoing CPM were younger than those who did not choose CPM. On unadjusted analysis, mean breast satisfaction was higher in the CPM group (60.4 v 57.9, P < .001) and mean physical well-being was lower in the CPM group (74.6 v 76.6, P < .001). On multivariable analysis, the CPM group continued to report higher breast satisfaction (P = .046) and psychosocial well-being (P = .017), but no difference was reported in the no-CPM group in the other QOL domains.

Conclusion: Choice for CPM was associated with an improvement in breast satisfaction and psychosocial well-being. However, the magnitude of the effect may be too small to be clinically meaningful. Such patient-reported outcomes data are important to consider when counseling women contemplating CPM as part of their breast cancer treatment.

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Study of patients with melanoma finds most have few moles

Gellar. A. C. et al. JAMA Dermatology. Published online March 02, 2016

B0006879 Skin cancer cell
Image source: Ann Weston CRUK – Wellcome Images

Image shows a scanning electron micrograph of a skin cancer cell derived from a cell culture grown from a human melanoma cell line.

Importance: Nevi are among the strongest risk factors for melanoma. However, little is known about the association of many total nevi (TN) or atypical nevi (AN) with tumor thickness.

Objectives: To examine the association between age and the number of TN and AN and to explore whether there was a relationship between TN or AN and tumor thickness, controlling for multiple variables.

Design, Setting, and Participants: Survey of patients with melanoma at 2 academic sites and an affiliated Veteran Affairs medical center. Participants included 566 patients surveyed within 3 months of diagnosis. Patients were surveyed in the melanoma clinics from May 17, 2006, through March 31, 2009, within 3 months of diagnostic biopsy. The dates of the analysis were April 1, 2015, to August 1, 2015.

Main Outcomes and Measures: Counts of TN and AN were performed at the first visit after diagnosis and were categorized as 0 to 20, 20 to 50, or more than 50 for TN and as 0, 1 to 5, or more than 5 for AN. Tumor thickness was categorized as 2.00 mm or less or as 2.01 mm or greater. All analyses were stratified by patient age (<60 or ≥60 years). Logistic regression was used to test associations, controlling for age, sex, anatomic location of melanoma, institution, histologic subtype, marital status, performance of skin self-examination, number of health care visits in the past year, mode of melanoma discovery, and receipt of skin examination by a physician.

Results: The study population included 566 patients. Their mean (SD) age was 56.7 (15.9) years, and 39.0% (n = 221) were female. Of 566 patients, the number of TN was classified as 0 to 20 (66.4% [n = 376]), 20 to 50 (20.5% [n = 116]), or more than 50 (13.1% [n = 74]). Atypical nevus counts were 0 (73.3% [n = 415]), 1 to 5 (14.5% [n = 82]), or more than 5 (12.2% [n = 69]). For those younger than 60 years, the presence of more than 50 TN was associated with a sharply reduced risk of thick melanoma (odds ratio, 0.32; 95% CI, 0.12-0.81), and the presence of more than 5 AN compared with no AN was associated with thicker melanoma (odds ratio, 2.43; 95% CI, 1.02-5.75).

Conclusions and Relevance:  Most patients with melanoma had few nevi and no AN. In younger patients (<60 years), thick melanomas were commonly found in those with fewer TN but more AN, suggesting that physicians and patients should not rely on the total nevus count as a sole reason to perform skin examinations or to determine a patient’s at-risk status. Younger patients should be educated on the increased risk of thicker melanomas that is associated with having more AN.

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