Wednesday, 13 June 2018

42. Breast Cancer Good News!


Illustration: American Heart Association
The majority of patients with the most common type of breast cancer do not benefit from chemotherapy after surgery according to a comprehensive study.
A decade long multi-center study by the ECOG-ACRIN Research Group, involving 10,273 women with early-stage cancer at 1,182 treatment sites across USA, Australia, Canada, Ireland, New Zealand and Peru, showed conclusively that chemotherapy was unnecessary in 70% of cases.
The Stage-3 Trial findings were published in the New England Journal of Medicine last week following the trial leader’s presentation to the American Society of Clinical Oncology (ASCO) annual meeting.
Unlike many published clinical trial results which require many years of further study before findings are confirmed and validated, this trial’s results will have an immediate impact on global treatment practice for early-stage breast cancer.
Dr. Alistair Ring, a consultant oncologist at the Royal Marsden NHS Hospital, London, was upbeat about the potentially immediate impact on breast cancer treatment in the NHS. “I think this is a fundamental change in the way we treat women with early-stage breast cancer and will lead to a considerable number of women no longer needing to have chemotherapy.”
Up to 5,000 women in UK could now avoid the harrowing side effects from the toxic drugs used in chemotherapy, if this life-changing refinement of early-stage breast cancer treatment is followed across the NHS.
Until now, post-operative treatment included hormone therapy plus chemotherapy for women diagnosed with early-stage HR-positive, HER2-negative, axillary lymph node-negative breast cancer. This therapy combination was administered to these patients to inhibit cancer recurrence.  However the trial showed that invasive disease-free survival after treatment was almost statistically the same, whether patients had the combination therapy or hormone therapy alone.
There is an additional bonus this refined post-operative cancer treatment of hormone-only therapy will have for healthcare systems around the world: lower costs!
The NHS is struggling with the spiralling costs of cancer drugs used in chemotherapy. These drug costs inhibit the ability of an underfunded NHS to adequately invest in other cancer services.
Further Reading
Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer
TAILORx Trial result
Multi-national network of participating institutions.
Many breast cancer patients can safely skip chemotherapy, study finds.
Cancer drugs price rise ‘costing NHS millions’

Thursday, 7 June 2018

41. Immunotherapy future for breast and other cancers



ThUS National Cancer Institute’s, ((NCI),  development of a novel approach to immunotherapy, reported in the June issue of Nature Medicine, has been given wide coverage in the British press. It is an important step forward in our understanding of cancer mutation and treatment.
The complex trial approach was in fact a modified form of adoptive cell transfer, (ACT), which has already been effectively used in in skin cancer treatment trials.
The treatment trial on a patient with late-stage breast cancer led to the complete cancer regression in the patient who had been  unresponsive to all other treatments. All of the patient’s cancer, which had spread to other parts of her body, disappeared after the treatments and has not returned more than 22 months later.
This was an innovative experimental approach for one very lucky 52-year-old patient who had not responded to hormonal and chemotherapy, and whose condition had deteriorated to a point that she was planning her death after the cancer had spread to her lungs and liver.
Extensive and time-consuming multi-centre trials must now be undertaken to prove the treatment’s efficacy before it can be made routinely available to treat late-stage breast cancer patients.
“This is an illustrative case report that highlights, once again, the power of immunotherapy,” commented Tom Misteli, Director of NCI’s Centre of Cancer Research, (CCR) at Bethesda.  “If confirmed in a larger study, it promises to further extend the reach of this T-cell therapy to a broader spectrum of cancers.”
CCR’s Dr. Steven Rosenburg, the clinical trial leader, commented on the broad potential of this experimental trial approach: “Because this new approach to immunotherapy is dependent on mutations, not on cancer type, it is in a sense a blueprint we can use for the treatment of many types of cancer.”

Further Reading
Files 07.06.2018. Caring Cancer Trust

40. Blood tests show promise as early cancer screening process




Studies of a blood test for 10 different types of cancers show promise as an early cancer screening process before patients show symptoms, Dr Eric Klein from the Taussig Cancer Institute of Cleveland, USA, told members at the annual conference of the American Society of Clinical Oncologists, (ASCO), in Chicago last week.

The blood test, called a liquid biopsy, screens for cancer by detecting tiny bits of DNA released by cancer cells into blood. The liquid biopsy technology was initially used to monitor patients after they receive treatment for an advanced cancer to evaluate their treatment’s progress or detect a recurrence through increased cancer cell DNA.

In recently completed studies of blood biopsy tests at Dr Klein’s Cleveland Centre and at Stanford University, clinicians scrutinised the cases of more than 1,600 people, 749 of whom were cancer-free at the time of the study, and 878 of whom had been newly diagnosed with a cancer. Liquid biopsies correctly found cancer cell DNA in 80% of the 878 patients in tests for pancreatic, ovarian, liver and gallbladder cancers. The tests were less accurate with lymphoma, myeloma, bowel, lung, head and neck cancers with a low correct diagnosis ranging from only 56% to 77%.
Although promising, there is obviously a long way to go in research to achieve the desired positive or negative predictive values with liquid biopsies before we can safely implement such tests in any national screening programme. To illustrate, globally ovarian cancer has an annual incidence of approximately 12 cases per annum per 100,000 women. If the new test has only an 80% chance of detecting this disease, this would translate to a failure (false negative) to detect 1 in 5 of these cancers. Furthermore, if the test has a false positive rate of just 1%, this would mean incorrectly diagnosing 1000 women as cancer positive in order to detect less than 12 actual cancers.

So there is obviously considerably more research needed to clinically develop blood tests to a point where they can accurately detect a cancer. However, following on-going studies presented by Dr Vogelstein of John Hopkins School of Medicine to the conference in 2017, and by Dr Klein last week, further research could ultimately lead to the availability of an accurate universal blood test screening for cancer, enabling doctors to accurately detect a cancer in patients at what is presently an undetectable early stage.

“This is potentially the Holy Grail of cancer research, to find cancers that are currently hard to cure at an earlier stage when they are easier to cure,” said Dr Klein, lead author of the Taussig Centre study. “Potentially this test could be used for everybody. It is several steps away and more research is needed, but it could be given to healthy adults of a certain age, such as those over 40, to see if they have early signs of cancer. We hope this test could save many lives.”

As Dr Bert Vogelstein of John Hopkins Kimmel Cancer Centre pointed out at last years ASCO conference: “It’s fair to say that if you could detect all cancers while they are still localised, you could diminish cancer deaths by 90%.”

Studies at John Hopkins have indicated that while cancers of liver, stomach, pancreatic, ovarian, oesophagus, colon, lung and breast can be detected from cancer tumour DNA in the blood, not all tumour types can be accurately detected in this way. Their studies continue with gene-based cancer tests that work using bodily fluids and secretions as well as blood.

An accurate liquid biopsy cancer screening in the UK and consequent early treatment for cancer positives would save thousands of lives and millions of pounds. But the NHS is presently overwhelmed, understaffed and underfunded and, thanks to the ever-growing pressure of rising demand, it is not coping with acute cases, let alone belated or cancelled treatment and diagnostic procedures. And this does not include the potential cost of funding and operating universal blood tests for those people who don’t actually realise that they are sickening with a previously undetected cancer.

Perhaps, by the time accurate liquid biopsy tests envisaged by Drs Vogelstein and Klein have been perfected for cancer detection, we shall have an adequately funded and fully staffed NHS that can make them universally available to those over 40.

Extensive time-consuming clinical research into liquid biopsies is underway in USA and the University of Manchester’s Research Centre in UK to find that Holy Grail of accurate comprehensive early stage cancer detection by means other than X-rays, colonoscopy or pap smears. However Press headlines about cancer detection progress rarely mention the research timescales and cost. These studies take considerable time and money, as will the additional multi-centre research over the next five or ten years to evaluate and confirm a genetic blood test as fit for purpose, before any universal screening test can be implemented.
We need to keep funding this exciting research to advance the science of liquid biopsies. The research has come a long way in the past five years, but we still have a long way to go.
Further Reading
Filed 006.2018. Caring Cancer Trust

39. Be SunSmart this Summer!


Photo: Noosa, Australia
After a long winter, the prospect of a sunshine holiday looms large in our minds. There are however risk factors in acquiring that so-called ‘healthy tan’ from sunbathing.  Over-exposure to sunlight radiation can cause three skin cancers that can kill; (malignant melanoma, squamous, or basal cell carcinoma).
To quote the Cancer Council of Australia website, “A tan is not a sign of good health or wellbeing, despite many Australians referring to a ‘healthy tan’. Almost half of Australian adults still hold the misguided belief that a tan looks healthy. Tanning is a sign that you have been exposed to enough UV radiation (from the sun or solarium) to damage your skin. This will eventually cause loss of elasticity (wrinkles), sagging, yellowish discolouration and even brown patches to appear on your skin. Worst of all, it increases your risk of skin cancer.
In the UK at least 100,000 new cases of skin cancer occur each year, and the numbers are growing. The prime cause is UV exposure from sunlight.
The sun gives off ultra-violet (UV) radiation. This radiation is an invisible killer that you can’t see or feel. Over-exposure to UV causes early aging of the skin and consequent skin damage that can lead to skin cancer. It can also cause problems with the eyes and the immune system.
Avoiding sunburns and intermittent high-intensity sun exposure (especially in children, teens, and young adults) reduces the chances of getting skin cancer. Babies and young children can easily get sunburnt, which can result in the potential for a skin cancer in later life.
The US National Cancer Institute, (NCI), recommend that people of all ages and skin tones should limit the amount of time they spend in the sun, especially between mid-morning and late afternoon, (10am – 4pm when), and avoid other sources of UV radiation, such as tanning beds.
UV radiation is reflected by sand, water, snow, ice and pavement. It can go through windshields, windows and even clouds.
Even though skin cancers are more common among people with a light skin tone, people of all skin tones can develop skin cancer, including those with dark skin.
The NCI, British Skin Foundation and the Australian Cancer Council offer tips to be sun smart and protect your skin from UV radiation.
  • Wear a hat with a wide brim all around that shades your face, neck, and ears. Baseball caps and some sun visors protect only parts of your skin.
  • Wear sunglasses that block UV radiation to protect the skin around your eyes.
  • Wear long sleeves and long pants. Tightly woven, dark fabrics are best. Some fabrics are rated with an ultraviolet protection factor (UPF). The higher the rating, the greater the protection from sunlight.
  • The British Skin Foundation and Australian Cancer Council recommend that you use a sunscreen with a sun protection factor, (SPF), of least 30. Apply the product’s recommended amount to uncovered skin preferably 30 minutes before going outside, and apply again every two hours, or after swimming or sweating.

Further Reading
British Skin Foundation

Melanoma

Basal Cell Carcinoma

Squamous Cell Carcinoma

Australian Cancer Council                                                                    
US National Cancer Institute                                                                
 Filed 01.06.2018. Caring Cancer Trust

38. Exercise as cancer treatment and prevention



Photo: University South Australia.

Exercise is an essential component of successful Cancer treatment according to the Clinical Oncology Society of Australia, (COSA) latest  Position Statement, (18 May). It highlights the crucial exercise role in Cancer Care as adjunct therapy alongside surgery, chemotherapy or radiation.

Rest and activity avoidance were historically an integral part of Cancer Care. But evidence now indisputably confirms that every person with Cancer will, (and should), benefit from the prescription of a structured exercise medicine programme.
The days when we wrapped patients in cotton wool are gone, points out Dr David Speakman of Australia’s Peter MacCallum Cancer Centre. “Our attitudes to treating cancer, what it takes to give people their best chance at survival, have to change. All cancer patients will benefit from an exercise prescription.”
COSA Associate Professor Prue Corrie comments: “Really we are at the stage where the science is telling us that withholding exercise from cancer patients can be harmful. Exercise is the best medicine someone with cancer can take in addition to standard cancer treatments. That’s because we know now that people who exercise regularly experience fewer and less severe treatment side-effects; cancer-related fatigue, mental distress, quality of life. They also have a lower risk of their cancer coming back, or dying from the disease."
Writing in the Australian research analysis publication The Coversation, Professor Cormie lays out COSA’s new thinking on exercise medicine. “If the effects of exercise could be encapsulated in a pill, it would be prescribed to every cancer patient worldwide and viewed as a major breakthrough in cancer treatment. If we had a pill called exercise it would be demanded by cancer patients, prescribed by every cancer specialist, and subsidised by government.”
Cormie recommends that health professionals worldwide should view exercise as a standard part every Cancer treatment plan, enabling patients to be as physically active as their current ability and conditions allow. For significant health benefits, they should aim for at least 150 minutes of moderate intensity aerobic exercise weekly and two to three resistance exercise sessions (such as weightlifting).
I strongly recommend readers to watch Professor Cormie’s enlightening presentation on the Youtube excerpt or listen to her 20 minute podcast published by the MJA. They are featured below.
Further Reading
COSA Position Statement
Exercise in Cancer Care
Professor Cormie, Youtube
Exercise medicine for Cancer survivors

Filed 29.05.2018 Caring Cancer Trust

37. Treating Cancer with oncolytic viruses




We tend to think of viruses as disease harbingers. Oncology researchers have found however that some viruses can be modified in the laboratory to infect and kill Cancer tumour cells while not harming healthy cells.
A small but growing number of patients are benefiting from this new-targeted but presently exceedingly expensive viral treatment approach.
After a decade of research, the US Food and Drug Administration, (FDA), and the European Medicines Agency (EMA) approved T-VEC in 2015. This is an oncolytic virus modification based on the herpes virus and approval followed successful phase III multi-centre clinical trials on patients suffering from metastasic skin cancer. It was later given the green light by the NHS in UK for use on patients with inoperable malignant melanoma. Skin cancer that is now the fifth most common cancer in UK, with more than 14,500 diagnosed each year.
Oncolytic viruses, (OVs), used in virotherapy can not only kill cancer cells, but also trigger an immune response in the body against cancer. When a virus infects a tumour cell, the virus makes copies of itself until the cell bursts. The dying cancer cell releases toxic tumour antigens. These alert the body’s immune system and stimulate it to respond to the danger, not only from nearby cancer cells in the primary cancer site but of those that have migrated to other parts of the body in a secondary malignant metastatic growth.
These are still early days in oncolytic viral research and immunotherapy. But many more studies and clinical trials are underway across the world. They will provide insights into oncolytic virus use in combination therapies that not only kill cancer cells, but also enhance the body’s immune response to promote anti-tumour immunity.
Further Reading
OncoImmunology
Human Gene Therapy

Filed 02.04.2018 Caring Cancer Trust

36. Drug trial for aggressive breast cancer and hormone therapy




Approximately 10–15 per cent of breast cancer tumours do not respond to treatment with standard hormone therapy, which means that they are more aggressive and often recur.
An international research team led by Professor Kristian Pietras at Lund University, Sweden, has uncovered a way to treat these aggressive tumours through manipulation of the connective tissue cells of the breast cancer.
“Previously, it was believed that the various subgroups of breast cancer originated from different cell types in the mammary gland. Our research has shown that connective tissue cells can also modify tumour cells directly with regard to their sensitivity to hormones, which has significant implications in the development of more effective treatments”, states Professor Ulf Eriksson of Stockholm’s Karolinski Institute, who collaborated in the study.
The researchers tested a new biological drug they developed which blocked the PDGF-CC-mediated communication between the tumour cells and the connective tissue cells. This resulted in the transformation of the basal breast cancers into hormone-sensitive luminal breast cancers that were highly responsive to conventional hormone therapy.
“We have thus developed a new treatment strategy for aggressive and difficult-to-treat breast cancers that restores sensitivity to hormone therapy. These findings have major implications in the development of more effective treatments for patients with aggressive breast cancer”, concludes Kristian Pietras.
Following this study, the researchers are developing a new drug for trial which will transform aggressive breast cancer tumour so that they respond to standard hormone therapy.

Filed 26.03.2018. Caring Cancer Trust

35. Multi-targeted immunotherapy trial in Childhood Leukaemia


Lymphoblasts from an ALL patient stained in blue. Photo courtesy of Nirali Shah
Following news of a phase 3 trial of AstraZeneca’s experimental drug (In The News 23.03.18), we are notified of a new phase 1 clinical trial being conducted at Bethesda Hospital, Maryland, for acute lymphoblastic leukemia (ALL) treatment. It will use a double-barrelled approach that targets two proteins found on the surface of the cancer cells.
In ALL the bone marrow makes abnormally high levels of immature white blood cells called lymphoblasts. Using chimeric antigen receptor (CAR) T cells to attack Cancer cells has shown promise as an emerging ALL treatment and will be the approach used in this new trial.
In this trial therapy, headed by Nirali Shah M.D., of the US National Cancer Institute, CAR T cells—white blood cells that defend the body against disease—are collected from patients and engineered in the laboratory to express receptors that target the two specific proteins on the surface of cancer cells. The collected CAR T cells are prodded to proliferate in the clinic and then infused back into patients. The clinicians expect that these cells will further proliferate in the body, hone in on the cancer cells bearing the surface protein target and kill them.
70 - 90% of ‘ALL’ patients who have relapsed or become resistant to chemotherapy can achieve remission of their disease after receiving CAR T-cell therapy that targets a protein found on the surface of lymphoblasts. But 30 - 50% of these patients suffer a further relapse.
Success in this strategy of targeting two proteins simultaneously will bring CAR T-cell therapy closer to durable remission in the most common of childhood Cancers.

Filed 16 April, 2018, Caring Cancer Trust

34. Genomic Differences between Childhood and Adult Cancers



A recent pan-cancer study in USA published in Nature, 28 February, has found that several cancer types are genetically different in children and adults.
The paediatric study, led by Jinghui Zhang, Ph.D., at St. Jude Children's Research Hospital, Memphis, analysed samples from nearly 1,700 patients, aged 20 or younger, looking at all non-inherited, or somatic, genetic alterations. Adult patients in the TARGET study elsewhere in USA had common childhood cancers, including acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), neuroblastoma, Wilms tumour, and osteosarcoma.
The researchers identified 142 altered genes that drive the development of these cancers (driver mutations), of which only 45% are found in adult cancers.
The findings reinforce the growing belief that drugs developed and approved to treat cancers in adults may not always be effective or appropriate for children with the same cancer types, emphasising the need for paediatric cancer-specific development of precision therapies.
Further Reading
Nature, International Journal of Science.

Filed 24 April, Caring Cancer Trust.

33. Childhood Leukaemia Targeted Therapy Trialsdrug trial success


Photo: Rosewell Park Cancer Center, Buffalo, NY.
Stage 3 trials of an experimental targeted cancer drug produced by AstraZeneca that includes a bacterial toxin shows promise in treating the most common cancer in children, B-cell acute lymphoblastic leukaemia (ALL). However, therapeutic benefits in the trial appear to be limited, because trial patients are quickly developing therapeutic resistance to the drug and relapse.
A US trial however has shown that resistance to the targeted toxin-based therapy can possibly be overcome by combining it with another leukaemia drug, (Moxe), thus increasing its efficacy in patients with relapsed and chemotherapy-resistant (refractory) ALL.
Elsewhere Pilot phase 2 trials involving 154 children’s hospitals across USA are underway to test combination treatment for ALL, its infant tolerability and long-term event-free infant survival. The trials use a cocktail of targeted chemotherapy drugs that work in three different ways to stop cancer cell growth; by killing the cells, by stopping them from dividing, or by stopping them from spreading.
There is still a long way to go before the long-term efficacy of targeted drug combinations are proven, accepted and licensed by the FDA in USA and the NHS in UK for treating infant leukaemia.  Research clinicians however are showing significant progress in harnessing the body’s own defence system by using modified T-cell based therapy to attack and kill cancer cells in both ALL and other cancers; a radically different approach to previous conventional chemotherapy treatments.
Genetically modified so-called chimeric antigen receptor (CAR) T-cells are showing remarkable efficacy for the treatment of chemotherapy resistant relapsed B-cell ALL, and other cancers, although tumour cells still adapt to evade even this new type of treatment.  It is hoped that selecting the right combination of therapies will limit the ability of cancer cells to escape such combinatorial approaches to treatment.
Filed March, 2018, Caring Cancer Trust.

32. NHS RAPID pathway to prostate cancer diagnosis



A new pilot high-speed path to treatment for prostate cancer that can significantly cut diagnosis time was presented at the European Association of Urology Conference in Copenhagen in March by Professor Hashim Ahmed, Chair of Urology at Imperial College London.
The procedure can cut waiting time for detection in the UK from an average 56 days to 17 days after referral from GP. As the difference between early and late detection of the disease is a matter of life and death, this new rapid procedure could save many lives if rolled out by the NHS across the country in the 2020s, following clinical trials.
The new world-leading (magnetic resonance imaging (MRI) procedure, is completed in one day rather than several. It was successfully piloted at London’s Imperial College Charing Cross Hospital and Epsom Hospital in 2017. Some 4 in 10 patients are cleared immediately after their MRI scan and the rest have a precision biopsy using fusion technology later that same day.
Professor Hashim Ahmed to led the treatment trial said: “The NHS has led the research that underpins this RAPID pathway to improve the diagnosis of prostate cancer. The NHS is now leading the way in ensuring all men get to benefit from this innovation. Fast access to high quality prostate MRI allows many men to avoid invasive biopsies as well as allowing precision biopsy in those men requiring it to find high risk tumours much earlier.” access to high quality prostate MRI allows many men to avoid invasive biopsies as well as allowing precision biopsy in those men requiring it to find high risk tumour much earlier,”
Prostate cancer is now the second biggest killer for men after lung cancer. It kills over 10,000 men in UK, 28,000 in USA and 4,000 in Canada each year.

Filed 22 March 2018 Caring Cancer Trust

Monday, 1 January 2018

31. Breast Cancer Diagnosis Breakthrough

     



         Recent research led by University College London has identified a cancer signature in DNA changes apparent in blood tests. These signal a possibly fatal breast cancer symptom up to one year earlier than current medical diagnosis techniques which may still test negative in current breast screening.

     “This may enable individualised treatment, which could even begin in the absence of radiological evidence in the breast,’ UCL’s Professor Martin Widschwendler, who co-authored the study, has stated.
     Such early detection and consequent early hormone treatment could mean a difference between life and death. It would also eliminate the possibility of over-diagnosis and subsequent debilitating treatment of slow growing but benign tumours that are frequently detected in mammography screening.  
     Further study and trials are necessary before this early detection process can be made available on the NHS or in USA.
     Latest statistics show that 1 in 8 women in UK and USA will be diagnosed with breast cancer at sometime in their lifetime. Breast and lung cancers are, in fact, the foremost cause of female cancer death in these countries.
     The incidence of breast and lung cancer is in fact increasing, thanks to the growth and ageing of the population, together with an increasing prevalence of risk factors associated with economic growth and urbanisation, such as smoking, obesity, diet, and physical inactivity.
     As with all cancers, the risk of developing breast, (or other), cancer depends on a number of factors that are possibly outside your immediate control.  
     You can however eliminate the breast cancer risk by cutting alcohol out altogether, or at least down to the national guidelines, to ensure that you are not one of the 12,000 new cases of cancer in UK each year caused by alcohol, which include cancers of the mouth, throat, larynx, oesophagus, breast, live and bowel.
     Post-menopausal women who are overweight or obese are also at increased breast cancer risk.  Since both alcohol and obesity significantly increase the risk factor for a large number of cancers for both sexes at any age, you can do yourself a big favour if you over-indulge on the booze and/or are overweight by changing your lifestyle.
1.    Cut down on the booze!
2.  Change your diet to lose weight!
     3.  Get out and stretch those legs! 

Ian MacWatt
Further Reading

     Methylation patterns in serum DNA for early identification of disseminated breast cancer. Report on the UCL Study.
     Lung cancer and breast cancer; the leading cause of female cancer death in developed countries.                                                                                        
     Cancer Prevention
     Obesity and Cancer
     Alcohol and Health.
Nature
     Alcohol damages DNA and increases cancer risk


Filed March 2018 Caring Cancer Trust