Paediatric Brain Tumours

Advances in our Understanding of Paediatric Brain Tumours

By Marc Hendricks

Massive advances have been made in the last forty years in paediatric oncology. The best example of this is in acute lymphoblastic leukaemia (ALL) which is the most frequently diagnosed malignancy in children and which in the early 1970s was almost uniformly fatal. Today in developed nations the overall survival for ALL tops 80%, in some countries as high as 90%. Almost every other solid paediatric tumour has followed suit except for paediatric brain tumours, which despite comprising a third of all tumours seen by paediatric oncologists, was the group in which arguably there was the slowest progress by comparison.

Recently however, the advent of molecular mapping of paediatric brain tumours has transformed the landscape of our conventional ideas of risk stratifying children with brain tumours which traditionally was built on the prospect of resectability of the primary tumour, the presence or absence of metastatic disease and the histology of the tumour.

The two most recent examples which best demonstrate this seismic shift in our understanding of paediatric brain tumours is undoubtedly the new molecular risk stratification groups which have emerged in paediatric medulloblastoma (Kool et al., 2012Taylor et al., 2012) and the removal of the term primitive neuroectodermal tumour (PNET) from the WHO classification, following emerging studies from Sturm et al. (2016) revealing multiple molecular sub-types amongst tumours traditionally described as PNETs. Using DNA methylation profiling, the investigators were able to demonstrate amongst other things four distinct new categories of tumour each with its own recurring genetic alterations, histopathological signature and clinical characteristics.

This technology is unravelling almost faster than therapeutic interventions can keep up as new risk groups and sub-groups are identified through cutting edge laboratory work. International clinical trial groups have been quick to follow on the heels of these discoveries by incorporating molecular categorisation into new treatment protocols in order to learn more about the optimal management of these tumours. In addition, similar technologies are now being used in other groups of brain tumours with the hope that more can be learned particularly about tumours, which up to now have eluded clinicians, surgeons and radiation oncologists. This, in concert with advances in surgical and radiotherapeutic techniques, brings with it renewed hope that a new era in paediatric brain tumour management has dawned.

Source links: Kool et al. (2012)Taylor et al. (2012)Sturm et al. (2016).

del 16 in Acute Myeloid Leukaemia

del 16 in Acute Myeloid Leukaemia (AML) in children: Are the Clinical Implications for Management the Same as for Other Good Risk Cytogenetic Myeloid Leukaemias in Children?

By Marc Hendricks

Recently del 16 has been described in AML in children and adults. According to current guidelines risk stratification for paediatric myeloid leukaemias is based on cytogenetic profiling. Patients with leukaemia with good risk cytogenetic profiles are treated with intensive chemotherapy alone and are not considered candidates for transplantation in first remission. These karyotypes include t(8;21), inv(16), t(16;16) previously described in the association with historical French-American-British M4Eo and t(15;17) in acute promyelocytic leukaemia (APL) along with the other known microvariants.

With the description of the del 16 questions have been raised about whether or not this specific genetic abnormality constitutes a newly discovered good risk variant and whether the same treatment algorithm can be followed as for the other favourable cytogenetic group. The distinction is an important one because it speaks to the need for transplantation to consolidate a remission following intensive chemotherapy: in other words, can transplant be avoided or should children with del16 rather be assigned to a standard risk group and should practitioners then be looking for HLA identical donors to proceed to transplant?

Considering the small number of reported cases there is, as yet, no clear indication that the deletion is interchangeable (as it refers to risk) with inv16 and t(16;16). The source links provided highlight the recent descriptions and the controversial question that it has raised for the management of myeloid leukaemia in children.

Source links: Arthur and Bloomfield (1983),  Rogers et al. (2017)Silva et al. (2004).

HPV Testing in Cervical Cancer Screening

HPV Testing Alone is Better than Co-testing with Pap Smear for Cervical Cancer Screening

By Ramadhani Chambuso

Despite huge research into HPV and the introduction of preventive HPV vaccines, cervical cancer screening will remain important and comprise many millions of tests annually for decades to come.

Screening by HPV testing, which detects a cervicovaginal specimen for the presence of the nucleic acids of carcinogenic types of HPV, is more sensitive than the Pap test which is a microscopic examination of exfoliated cervical cells, for detection of cervical pre-cancers, a new study in the Journal of the National Cancer Institute finds.

However, the reports of rare HPV-negative, Pap-test positive cancers are motivating the continued use of both tests (co-testing) despite increased testing costs. In addition, the HPV test captures the known cancer causing viruses only, but it is believed that there may be other unknown cancer causing viruses and so continue to do the Pap smear plus the HPV testing is crucial.

Thus, if a single screening method were chosen to complement HPV vaccination, primary HPV testing likely would gradually supplant the Pap test.

Source link: Schiffman et al. (2017).

Bowel Cancer Screening Test

Simplified Test for Bowel Cancer Launched

By BBC Tayside and Central Scotland

Shared by Ramadhani Chambuso

Phyllis Weir
Phyllis Weir (centre) said the bowel cancer screening test had saved her life

A simplified screening test to detect the symptoms of bowel cancer has been launched in Scotland following a successful pilot.

The new test only requires collecting one stool sample compared to the six separate samples previously required.

The test will be offered every two years to all men and women in Scotland aged between 50 and 74.

It is hoped the easier process will encourage more people to participate in the screening test.

Bowel cancer is the third most commonly diagnosed cancer in both men and women in Scotland.

About 3,700 new cases were diagnosed in 2015, with 95% of cases occurring in the over-50s.

The UK National Screening Committee recommended that the test is rolled out nationally after a pilot involving 40,000 people.

‘Save your life’

Phyllis Weir from Lanark was diagnosed with bowel cancer in 2013 after taking the screening test.

She told BBC Scotland: “I was shocked at the fact I had bowel cancer because I had absolutely no symptoms at all.

“I would urge people to take this test because it can save your life.

“I wouldn’t be here today if I hadn’t taken the test.

“I have spoken to so many people since then who would still have their tests sitting in their bedroom drawer if they hadn’t heard my story.”

Visiting the Scottish bowel screening lab in Dundee’s Ninewells Hospital, Health Secretary Shona Robison said: “Early diagnosis is crucial to saving lives.

“More than 90% of bowel cancer cases can be treated successfully, if diagnosed early.

“The new test is easier to use than the previous process and this will increase the number of people completing screening.

“This will enable us to detect more conditions at an earlier stage, helping more people to beat bowel cancer than ever before.”

Source link: BBC Tayside and Central Scotland.

HBV Vaccination: Protection against Lymphoma Development

Hepatitis B Virus Vaccination is Protective against Lymphoma Development, a Study Finds

By Ramadhani Chambuso

Hepatitis B virus (HBV) infection has been documented as a risk factor for a certain type of blood cancer called non-Hodgkin lymphoma (NHL), worldwide.

Recently, a large cohort epidemiological study involved a database of one million people for sixteen years, reports that HBV vaccination is protective against lymphoma development in the teenagers in an endemic area in Taiwan, however they suggested longer follow-up is required for older age individuals.

Furthermore, they found that HBV infection increased the risk for developing NHL and specific aggressive lymphoma, with Hazard Ratios of 4.14 and 5.52, with a higher incidence of 17.07 and 13.9 per 100 000 person-years, respectively, compared to the non-HBV cohort.

Interestingly, this study demonstrates, for the first time, universal HBV vaccination reduces the incidence of NHL in adolescent and young adults less than 20 years. Further, it suggests that cancer prevention through HBV vaccination is not only for hepatocellular carcinoma but also NHL in endemic areas of HBV infection.

To conclude, this evidence suggests that HBV could be an etiologic factor for NHL and CD20+aggressive lymphomas, although confirmation of the mechanism needs further studies.

Source link: Huang et al. (2017).

Personalizing Cervical Cancer Screening Based on HPV Vaccination Status

Cervical Cancer Screening Should be Individualized for Women Vaccinated Against High-Risk HPV

By Ramadhani Chambuso

Appropriate cervical cancer screening intervals for women vaccinated against high-risk HPV are yet to be well established and an updated screening algorithm has not been agreed worldwide.

However, a recent simulation study done in England found that the necessary number of lifetime screens for HPV16/18-vaccinated women and HPV16/18/31/33/45/52/ 58-vaccinated women were three for cervical cancer prevention in HPV16/18-vaccinated women, while just two for HPV16/18/31/33/45/52/58-vaccinated women.

Furthermore, these researchers used a microsimulation model calibrated to real published data to determine the appropriate screening intensity for vaccinated women. As well the natural histories in the absence of vaccination were simulated for 300,000 women using 10,000 sets of transition probabilities.

In addition, the linkage of vaccination status to the screening programme was done, a process already recommended earlier in England. For example, the current US guidelines recommend the same screening intervals for women regardless of vaccination status, though this is likely to be updated once vaccinated women enter screening and the data have been evaluated. Assuming future cervical screening guidelines differ for vaccinated and unvaccinated women, countries which do not have a good record of who received the HPV vaccine may wish to consider the potential use of HPV antibody testing as part of a future cervical screening programme.

Therefore, these results clearly demonstrate that the cervical cancer screening programme should be personalised based on HPV vaccination status.

Source link: Landy et al. (2017).

Breast Cancer Targets

Tumor Infiltrating Lymphocytes may be Predictive in African-American Women with Triple-Negative Breast Cancer

By John Schieszer

Shared by Paul Mambwe Chilwesa

High levels of peripheral tumor infiltrating lymphocytes (TILs) may be associated with better prognosis among African-American women with triple-negative breast cancer (TNBC) in the early stages of the disease, according to researchers at Emory University. They reported at the American Association for Cancer Research (AACR) Conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved in Atlanta that clinicians may want to consider screening some African-American women with breast cancer for levels of TILs.

“Screening early-stage African-American triple-negative breast cancer patients for levels of tumor infiltrating lymphocytes in the clinic may provide a method for oncologists to predict patient prognosis and devise an optimal treatment plan for these patients at risk for poorer outcomes.” said the study’s lead author, Nikita Wright, BS, a PhD candidate at Georgia State University, Atlanta, Georgia.

TNBC is a highly aggressive breast cancer subtype that afflicts African-American women at a higher rate than white women. Wright said it often involves a worse prognosis and previous research has shown that African-American women tend to develop more aggressive subtypes of TNBC than European-American women, exacerbating the disparity in survival.

“There is a great need for robust, clinically translatable prognostic biomarkers and/or new therapeutic targets for triple-negative cancer patients and especially for those of African descent, who display a more aggressive disease course,” Wright told OncoTherapy Network. “Analyzing racial disparities in the tumor micro-immune environment between African-American and European-American triple-negative breast tumors may allow us to harness the potential prognostic utility of tumor infiltrating lymphocytes as well as their value as a treatment target for promising immunotherapeutic agents.”

Wright and colleagues tested resection samples from 142 TNBC patients and compared stromal TILs between patients of African-American and European-American descent. None of the patients had undergone neoadjuvant chemotherapy. The study showed African-American women harbored significantly more overall TILs than European-American patients. Significant differences were also observed among early-stage TNBC patients, but not among late-stage patients. The study showed that high peripheral TILs were associated with better 10-year survival among early-stage African-American TNBC patients after adjusting for age, Nottingham grade, and stage.

A greater presence of overall and peripheral TILs were also associated with a lack of androgen receptor (AR) expression among African-American patients with early-stage TNBC. Wright said the lack of AR reception classifies some TNBC cases as quadruple-negative, and this subtype is more prevalent among African-American compared with European-American TNBC patients. In addition, she said that among African-American patients with early-stage TNBC, high TIL counts were also associated with younger age at diagnosis, increased intramammary lymph node involvement, and increased BRCA1-associated protein and programmed cell death protein 1 expression.

“Adoptive cell therapy with tumor infiltrating lymphocytes are currently being tested in clinical trials as a treatment option for breast cancer patients to shrink breast tumors and have already shown promising results in melanoma patients. If approved, administering immunotherapy with tumor infiltrating lymphocytes to early-stage African-American triple-negative breast cancer patients may improve outcomes in this patient population and attenuate racial disparities in triple-negative breast cancer,” said Wright.


The Secret Suckiness of Life after Breast Cancer

Shared by Ramadhani Chambuso

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November 2017
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