Thursday, 17 November 2011

More on the NCRI Conference

I have just completed the feedback survey for the conference and when asked what was the most important  thing I'd gained, my answer was: a better understanding of the role of stratified medicine. To a greater or lesser extent it underpinned all of my "top three conference sessions".

As I said in my overview of the event, stratified medicine was a theme that emerged from a number of the sessions covering different cancer sites and treatments. The scene was set for me by an excellent session on the Monday morning and titled simply "Stratified medicine". The first speaker was Albert Bardelli, from University of Torino Medical School, Italy. He spoke about personalised treatment in colorectal cancer, mentioning that one targeted therapy only benefits about 10% of predicted patients in the absence of further selection. He also made the point that it may well be that not all mutations are "equal". He was followed by Jean Charles Soria, from University XI, Paris. This presentation was about selecting the right therapies for lung cancer patients based on predictive molecular markers. He also highlighted the need for molecular input into multi-disciplinary meetings. The final speaker was David Gonzalez de Castro, from the Royal Marsden in London. He made the observation that molecular markers are only of use if the appropriate drugs are available. He then proceeded to provide a kind of checklist:

1. Find the target
2. Know your enemies & friends (+ve and -ve predictive markers)
3. Put the findings into context
4. If it is stubborn, hit it again! And it may be possible to go back to earlier treatments.

The next in my Top Three was later in the day and had a much more lengthy title - Moving Towards a Molecular Rather Than a Risk-based Approach to Selecting Breast Cancer Patients Who Won't Benefit from Standard Treatment. This was hosted by David Cameron from the University of Edinburgh, who pointed out in his introduction that breast cancer is an area where a stratified approach has been validated  in the now routine hormonal and HER2 targeting; with newer therapies now being developed for further sub-groups. John Yarnold from the Royal Marsden spoke first and covered the possibility of reducing the burden of radiotherapy. This was in terms both of optimising hypofractionation, partial breast radiation and dose distribution, and in identifying who doesn't need radiotherapy. He touched upon predictive markers for adverse effects.

Next was Luca Giani from Milan, who pointed out that a one-size-fits-all approach to treatment results in both over and under treatment. He made the points that ER, PR and HER2 status alone don't coincide with the molecular subtypes, and that fewer people benefit from chemotherapy that receive it under current guidelines.

The final speaker for this session was Michael Lisanti from Philadelphia. He presented a parasitic model of cancer with mitachondria powering cancer cells and the possibilities for blocking this activity.

One of the reasons that I found this session particularly interesting is that it presented a sound scientific challenge to the view often seen expressed on breast cancer fora by those having treatment for breast cancer that they want to "throw everything at it". As we all know, treatments have side effects and while some are "only" (!!!) unpleasant, others are life-threatening in the short, medium and long terms. People can and do die as a result of treatment or end up with more limited options in the event of recurrence or metastatic disease. So identifying those for whom a possible treatment is going to have no effect is important. There is no point in "throwing at it" something that will be of no benefit but which carries a serious health risk. I think that is why I find the advances in stratified medicine so exciting.

The last of my Top Three was the Wednesday session on genetic predisposition and the implications for screening, surveillance and management. It considered breast, ovarian, prostate and colorectal cancers. It opened with Douglas Eaton from the University of Cambridge and included mention of one of the studies in which I have taken part. He spoke about the three main areas of genetic risk for breast cancer: the rare high risk mutations (such as the well known BRCA 1 and 2 gene mutations), the rare moderate risk ones and the common low risk mutations (of which 23 have been found so far with more to come). Different loci carry different levels of risk and can also predict ER status. This could possibly be used to inform decisions on the preventative use of drugs such as tamoxifen. Risk with the common low risk mutations is polygenic and the variants combine multiplicatively. Moreover, genetic risk seems to combine multiplicatively with other risk factors (such as mammographic density). About 200 loci for common cancers have been identified so far.

The second speaker was Harry de Koning from Rotterdam. He discussed issues concerning screening starting with the point that screening programmes are directed at those of average risk, relating this particularly to breast and colorectal cancers. In higher risk populations there can be important differences that might suggest different guidelines for different groups. He illustrated this with guidelines for BRCA 1 and 2 mutation carriers. Screening guidelines are the same, but there is evidence to suggest that while adding mammography to MRI for BRCA1 mutation carriers under 40 gives little benefit, it can contribute to detection of breast cancer in BRCA 2 mutation carriers. There is a need for further work on optimal screening for mutation carriers aged over 60.

The final speaker was Mark Robson from Memorial Sloan-Kettering in New York. He spoke about germline information being used to inform local, systemic and follow-up decisions. In particular it can be useful to know the risk of a second primary - not least because reconstruction options may be more limited after radiotherapy. It was interesting to hear him say that at his Centre the prophylactic mastectomy rate is high and although it wasn't always clear that surgical options had been fully discussed, that was driven by the women themselves (who presumably see no need to have lengthy discussions when they have already decided upon their course of action). He also touched upon germline defects being used as therapeutic drug targets. It has been suggested that BRCA 1 mutation cancers might be hyper sensitive to platinum, although that isn't completely clear. They do seem to respond well to taxanes. This is less so for BRCA 2 mutation cancers, where pathological complete responses are less common.

Other aspects were the possibilities of variants being implicated in radiation-induced tumours and in anthracycline cardio-toxicity.

Those were certainly the highlights for me, but I also attended some very interesting plenaries and sessions on screening and prevention, improving cancer survival, survivorship research, and cancer care as disease rather than discipline based. There was a session in which patients shares their experiences of being involved in clinical trials.

I would like to have attended (but couldn't because I was in another session): Improving design and analysis of early phase trials, Raising awareness of cancer research, Lifestyle factors in prevention, Spotlight on survivorship, and Radiotherapy: the quiet revolution.

1 comment:

  1. This is SO interesting - I have learned such a lot from this.

    Thanks so much for taking the time and energy to share these insights.
    P x