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MD-FM Oncology with the Audio Journal of Oncology, Friday April 4th, 2013


GENERIQUE
Carillon
 
Sarah:

MD FM with the Audio Journal of Oncology: cancer news from around the world with Peter Goodwin.
 
P1
PETER:
Hello. And with me is Sarah Maxwell.

A new way of monitoring how well treatment is working in patients with metastatic breast cancer has been reported, in the New England Journal of Medicine, by a group at Cambridge University in the UK.

SARAH:
Yes, and if it fulfils the promise it’s shown in early tests on 30 women it could verify whether or not a drug is effective within days instead of having to wait months for radiographic evidence.
The blood test detects circulating free tumour DNA; and Dr Dana Tsui told us what they found:

Bob 01 - DANA TSUI 01
If the patient is not responding to treatment we can actually detect an increase of the tumour DNA marker months before CT scan. So that is very important because it means that we can actually do something early enough while the treatment is not effective

PETER:
But you can track circulating tumour cells or antigens in the blood can’t you?

SARAH:
Oh yes. And the Cambridge group tested for these as well, on the same women, make a comparison. And the found the free DNA test was far more powerful, making it potentially of great value in the clinic!
Dr Tsui thought it could help patients avoid unnecessary treatment: being treated with drugs that don’t work:

Bob 02 -DANA TSUI  02
We can potentially use it to tailor make treatment for patients which means personalised treatment, which I think is very promising because then it means that we can potentially stop the patient from receiving unnecessary treatment which bring bad side effects and also if we can pick up new genetic information in the blood then it potentially means we can change the treatment to other more effective treatment that would be beneficial to the patient

SARAH:
Dana Tsui from Cambridge University and Cancer Research UK. And she mentioned that the sophisticated DNA science they’re using offers hope of finding new targets for treatment.

Well the editorial comment on these findings in the New England Journal was written by Dr Marc Lippman from Miami. What did he think were the potential strengths of the new test?

Bob 03-MARC LIPPMAN  01
I think that the biggest assets would be two:  One, a very early indication as to whether or not a therapeutic intervention was working or not. I think that would be terrific if that turns out to be the case – as I said they provide preliminary data on that but: a great deal more will need to be done. I think where this is really going to be of great interest is, if the test really is sufficiently sensitive, to discover, for example, whether surgery is adequate: whether a patient needs adjuvant chemotherapy, whether or not this test will remain positive with levels of tumour that would potentially be curable in the adjuvant setting but are below some level of detectability.  Alternatively: conceivably if the test was dead negative it might say the patients who were otherwise to receive additional systemic therapy might not need it

SARAH:
Marc Lippman from Sylvester Comprehensive Cancer Center at the University of Miami

VIRGULE MUSICALE

P2
PETER:
Cancer risks and cardiovascular risks seem to go hand in hand.  More on this from the 2013 St Gallen Conference on: Primary Therapy of Early Breast Cancer”

SARAH:
Dr Rowan Chlebowski told his audience in Switzerland why walking the dog could be good for treating breast cancer and how the Women’s Health Initiative study, looking at lifestyle factors and their relationship with breast cancer gave insights into the role of both exercise and obesity in cancer prevention and therapy:

Bob-04 ROWAN CHLEBOWSKI  01
For breast cancer risk it really looks like there’s a very strong association with obesity, and also with physical activity. And interestingly the physical activity doesn’t have to be intense. It has to be walking three to four hours, regular pace, per week. Almost everybody should be able to do that

SARAH:
And he’s not advising you to do marathon races!!

Bob- 05 ROWAN CHLEBOWSKI 02
People walking three to four hours a week had maybe thirty to fifty per cent lower chance of recurrence

PETER:
But exercise and obesity are linked, and obesity is involved with oestrogen levels, isn’t it?

SARAH:
Yes and that’s because fat tissue generates oestrogen. Also at the St Gallen meeting Rowan Chlebowski commented on the influence obesity has on the choice of hormonal adjuvant therapy in breast cancer. Despite the advantages that aromatase inhibitors have shown over tamoxifen in some patients, in the case of patients who are obese, it seems, you have to choose your AI carefully

Bob- 06 ROWAN CHLEBOWSKI 03
There’s data suggesting that anastrozole was not better than tamoxifen in women who were overweight or obese in this big ATAC trial.  And in the BIG 1-98 trial letrozole was better than tamoxifen in women who were overweight or obese. I mean that’s simplifying the whole area but letrozole also surpressed, as was pointed out, estrogen levels greater than anastrozole. So in the absence of further data I think letrozole is the safer bet for women who are overweight or obese although questions still remain

SARAH:
That was Rowan Chlebowski from the Harbor UCLA-Harbor Medical Center in Los Angeles. He was talking with us at the St Gallen conference on primary therapy in early breast cancer in Switzerland.

VIRGULE MUSICALE

P3
PETER:
Another important cancer  conference: the ASCO Genito-urinary symposium, held in Orlando, Florida, has been hearing encouraging news about treating prostate cancer.

SARAH
There was quite a buzz at the GU meeting about treating so-called “castration-resistant” prostate cancer — which was considered to be no longer hormone responsive.  But apparently, not so, said Cora Sternberg from Rome whose group reported on the randomised AFFIRM trial using the oral drug enzalutamide:

Bob 07- CORA STERNBERG 01
Enzalutamide is a novel hormonal therapy and what we’ve learned over the last few years is that prostate cancer from the beginning until when patients become castration resistant and even after they’re castration resistant the disease is still driven by the androgen receptor and we’ve thought that the patients had what we call castration resistant prostate cancer when they no longer responded to hormonal therapy

 
SARAH
And the results are pretty impressive, a big step up from the placebo arm, which would represent the equivalent of standard therapy for most patients up to now!

Bob 08- CORA STERNBERG 02
We found a 37 per cent reduction in the risk of death in those patients randomised to the enzalutamide arm


SARAH:
So what would be Professor Sternberg’s recommendations to cancer doctors everywhere about potentially using this drug?

Bob 09- CORA STERNBERG 03
This is a very, extremely interesting drug that has now been shown in the AFFIRM trial and has been approved for patients after chemotherapy. We are waiting for the results of the PREVAIL trial which is a study in which we randomised patients who were asymptomatic or only barely symptomatic to enzalutamide versus placebo prior to chemotherapy and the field is changing.  People are giving chemotherapy later and later because these non-toxic hormonal therapies can be given to patients rather than chemotherapy we don’t have the results of those trials yet.

SARAH:
Cora Sternberg, Professor of Medical Oncology at the San Camillo & Forlanini Hospitals in  Rome. And our scientific editor George Canellos was impressed:

Bob 10- GEORGE CANELLOS
Really the interesting part was the biological reference to the fact that the androgen receptors still firing off and governing the proliferation of the tumor cells in patients who have resisted to castration.  If that is true, and it seems to be true, then these potent androgen receptor inhibitors coming along, and enzalutamide is probably just one of them, is fascinating. And the fact that you can pick up a patient who has failed chemotherapy, and the age of most patients being upper rather than lower these kind of sophisticated hormonal manipulations will go a long way

SARAH:
Dr George Canellos, from the Dana-Farber Cancer Institute in Boston.  

PETER:
Also at the GU meeting in Florida we were reminded that men with low-risk prostate cancer are more likely to die with prostate cancer than of prostate cancer.  

SARAH:
And this is especially true in older men, and in men who have a lot of health problems. According the merit-award winning scientist Ayal Aizer talking at the Orlando conference this is a group of patients who need active surveillance rather than aggressive treatment, which could have side effects like impotence and incontinence, could cost a lot, and all without extending life!  

 
VIRGULE MUSICALE
 
P4 
PETER:
If you screen most men for prostate cancer you’ll end up with lots of clinical decision-making that’s going to be tough. Similarly there’s always been controversy about breast cancer screening:

SARAH
Yes, and this was scrutinised at the 2013 St Gallen Breast Cancer Conference. Delegates in Switzerland heard that the benefits of mammography might be less than we often think…”

Bob  – DONALD BERRY
There’s becoming a recognition both in the united states and UK and other countries that screening is oversold. It is not as effective as many would have it believe. It is effective, I think that’s pretty clear, the question is whether it’s effective enough to use for younger women for older women is still a very big controversy

PETER:
That was Donald Berry from the department of biostatistics at the MD Anderson cancer center in Houston, texas. He’d been explaining to his audience in Switzerland the various types of bias that can make mammography seem more useful than perhaps it is. For one thing there’s selection bias, women who decide to get screened aren’t representative of the community as a whole. Then theres lead time bias:

Bob  – DONALD BERRY
If a woman gets a screening mammogram and they find it at, lets say: age 50, had they not done the screen, maybe it would have become evident at lets say ages 55. So that woman if you follow her for mortality is going to live five years longer automatically just because it was detected by screening even though theres no benefit for the screening itself.

PETER:
Another confusing factor is length bias, rapidly growing tumours aren’t in the breast for long before they’re clinically evident and so they can be missed while the slower growing tumours sit around longer:

Bob  – DONALD BERRY
The breast cancers today, have much better prognosis. The predominant reason is that the cancers that are found, tend to be more slowly growing. When a cancer is in the body and nobody is looking, it may stay in there for years where as if you do a screen you find that slowly growing tumour and that by definition is not going to be as aggressive as one that was only detectable only for a short period of time.

PETER:
As well as this, mammographically detectable tumours grow for unknown lengths of time before they’re big enough to be detected. If they haven’t metasticised by this time screening is a benefit and the evidence Dr Berry said in St Gallen, is that current guidelines are good. By annual screening for women over 50, with women under 50 recommended to have individual counselling because of the more questionable benefits for most of them, however:

Bob 16 – DONALD BERRY
The physicians should inform the woman of the negatives associated with screening. And there are many negatives there’s over diagnosis, there’s over treatment, there’s false positive’s and these are addressed by the taskforce recommendations. So I think it’s quite appropriate to be screening women let’s say between 50 and 70, I would stop at 70 they said 74. Once you get older first of all the tumours tend to be less aggressive, also with treatment we can extend it until the woman dies of something else.

SARAH:
Donald Berry, from the Department of Biostatistics at the University of Texas MD Anderson Cancer Center in Houston. He was talking at the St Gallen Conference on primary therapy of early breast cancer.


BREVE 1 -59 mots Sur fond musical
 
PETER:
Finally, in brief:

Treating patients who have breast cancer with bisphosphonates to control bone turnover has the effect of slowing down the metastatic process, according to findings from the AZURE study reported at the breast cancer meeting in St Gallen.  But Professor Rob Coleman warned that the benefit is restricted to post-menopausal patients.  Using these drugs in younger patients can have an increase in local and regional recurrence: findings consistent with those of five other studies.  

And...
 
BREVE 2

And an important development for cancer doctors wanting to reduce the intensity of treatment for children and young adults with acute lymphoblastic leukaemia in remission.  According to a paper in Lancet Oncology treatment intensity could be adjusted safely for children and young adults according to risk stratification based on minimum residual disease, bringing the prospect of reducing toxicity and improving quality of life.

That's all from this edition of MDFM with the Audio Journal of Oncology. More in a month’s time from Sarah Maxwell and from me Peter Goodwin.  So until then, goodbye!
 
JINGLE FIN     

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