In my speciality of oncology things can get pretty emotive. After all, when it comes to cancer we are dealing with life on death. Famously Nixon declared war on cancer and that war, along with many personal battles, continues to this day.

In keeping with the emotive nature of the war on cancer we use language that reflects war. Treatments, especially surgery, are frequently described as aggressive or radical, e.g. radical prostatectomy or modified radical mastectomy. Medical therapies are now called targeted therapies as though be remote control the doctor can target the drone and its’ weaponry to the cancer.

These terms do in some cases do accurately describe the personal attitudes of practitioners: some are more aggressive (or proctive) and others more conservative. However, the use of therse terms for the description of individual procedures is not justified.

My main practive is in treating peritoneal surface disease – cancer that infiltrates the peritoneal cavity. This can be treated by removing all of the cancer and in the case of many units we administer heated chemotherapy into the abdomen at the time of the operation. Because the surgery is a big, long operation and can be associated with significant morbidity it is often called aggressive or radical. There is even a committee being established in New South Wales to oversee ‘radical peritonectomy surgery’.

The clear counter argument to calling this surgery radical is ovarian cancer surgery. Ovarian cancer is traditionally treated with total abdominal hysterectomy and bilateral salpingo-oophoerctomy or removing the womb and ovaries. This is accompanied by omentectomy. Generally, when conducted by most gynaecological oncologists any disease in the upper part of the abdomen is left behind – in other words all of the cancer is not removed. There approach ignores research that demonstrates that women who have surgery to remove all of the cancer including cancer in the upper abdomen have better survival and not much more morbidity than conventional surgery. The operation required is complete cytoreduction or what we commonly call peritonectomy.

So should we call complete, or shall we say ‘adequate’ surgery for ovarian cancer ‘radical’ or ‘aggressive’ surgery? We could, but then we might also want a descriptor for the traditional operation: some options could be ‘complacent’, or ‘inadequate’, or ‘lazy’ or ‘conservative’ cytoreductive surgery. 

We should aim to get our terminology right as some patients will end up choosing less radical but also less effective treatment. 

There is currently a lot of angst as to why the Personally Controlled Electronic HEalth Record has not had massive uptake. This is hardly as surprise when NBN isn’t even close to being rolled-out but let’s look a little closer.

Sharing of medical records is often compared to internet banking: the banks can do it so why can’t health care deliver?

Point Number 1: Health care is not banking.

I see patients with cancer every working day and basically I feel confident in saying that until they get sick people actually pay more attention to their bank statements than their health. When you feel sick you feel sick and when you don’t , well, you don’t. But in banking you need to to know how much is in your account. People don’t feel this way about health.

Point Number 2: Consumer orientation is the wrong message.

The Government deliberately labelled the electronic health record as being ‘personally controlled’. The problem is that health care providers actually need to enter data and in many cases it is these providers that depend on the data…..as much as the consumer. In the case of banking both the banker and the customer want to know the balance and the history of transactions. Yes, make it seem the consumer is the focus but the reality is that PCEHR is a tool for communication between medical practitioner….incidentally, it’s so the consumer gets the best medical care. The real message is that PCEHR is for all of the stakeholders.

Point Number 3: Uptake is poor because it hasn’t been promoted well.

Most people actually haven’t heard of it. I tried to sign up and couldn’t because I didn’t have a recent Medicare transaction. People haven’t had a teaser. Inn the the case of internet banking there was the ATM. People trust ATMs to dispense their money and deal their transactions. Internet banking was a logical progression. There is no equivalent in health care. You can’t go to a box in a wall and check your health balance (yet). And who has seen an actual promotion for PCEHR? I’m aware of it but nobody has come out to me and said you must put this in your software.

My view is: make the approach to healthcare more like how we manage personal finance and then a PCEHR might get somewhere

John Corigliano Symphony No.2 and the Mannheim Rocket

Peteris Vasks Symphony No.2 & Violin Concerto Distant Light

One of the emerging treatments for cancers if immunotherapy that breaks the cycle of immunological tolerance that cancers create around themselves. Two key break throughs, anti-CTLA4 antibody therapy and anti-PD1 or anti-PD1L therapy have been shown to induce durable immune responses. In the case of the older treatment, anti-CTLA4 antibody therapy has now been shown to produce 25% and 20% 5 and 10 year survivals for metatatic melanoma – a disease usually fatal within 12 months of diagnosis.

Apart from the long term survivals there are two other exciting features of these treatments. Firstly  they can probably be used in most, if not all, cancer types although the chances of response does seem to vary. In the case of anti-PD1 therapy cancers such as NSCLC have response rates in excess of first-line chemotherapy. Secondly, early evidence suggests that these treatments can be combined safely and with much greater activity (doubling of monotherapy). At the moment there is no long term data around combination therapy. 

Let’s assume that combination anti-CTLA4 therapy and anti-PD1 therapy does provide long term ‘clinical cures’. A speaker at the meeting I was just at suggested 40-50% long term cure for metastatic melanoma. Based on the current pricing of ipilimumab (anti-CTLA4 antibody) then a combination treatment could well cost in excess of $250K per person. THis also may not abrogate the need for other targeted or chemotheapy and the immunotherapies tend to work slowly so patients presenting with advanced disease will still need initial therapy to control their tumour burden whilst the immunotheapy works.

If this strategy, for arguments sake, improved the median survival to 50-60% and the 10 year survival to 40% then investinging $250K upfront may well be cost-effective when translated into a cost per year of life saved – particularly if the treated population is of a productive tax-paying age.

But for Governments the upfront cost may still be too high if this treatment was applicable to all or most solid tumours. In part it may depend on how the regimen is ultimately delivered. If the therapy works with a short course of treatment and minimal or no maintenance therapy, and if additional theapies like targeted therapy or chemotherapy are not required then this treatment may well be viable. If many patients need additional targeted therapy or treatment escape is early then it may not be viable. Ideally poly-immunotherapy will increase survival and avoid the need for other costly therapies.

Ok – so I’m being a little lazy but I quite liked this article which highlights a skill not taught in medical school: the ability to negotiate, whether it be with patients or other members of the team. I spend a large amount of time trying to convince patients to either do something or stop doing something.

Negotiation strategies for doctors and hospitals

Conferences are vehicles for transfer of knowledge and new ideas. For scientific conferences like the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics meeting in Boston #Targets13 very specific information is communicated but what is perhaps more interesting is to try and spot emerging themes. One thing I’d say about this conference compared to last year and looking over the last few years of new drugs is that the era of targeted therapies is changing: let’s say we are moving from Targeted Therapy 1.0 to Targeted Therapy 2.0.

Over a decade ago I went to my first ASCO meeting and the excitement in the air was all about the new era of targeted therapy. Imatinib (Glivec) for CML and GIST was the poster child. Since that time there have been many new drugs that have come to market and now there is no common cancer and many less common cancers that have a therapy: tyrosine kinase modulation, angiogenesis inhibition and immunomodulation have all been validated.

Yet there is a big ”but” which is that the imatinib story is the exception rather than the rule. Imitanib targeted dominant driver molecular changes in the malignancies in which it was active. For most of the other targeted therapies the individual molecular targets were not dominant drivers. The consequence is that the majority of the targeted therapies since imatinib have generally translated into only modest improvements in clinical outcomes like PFS and OS and this is often the case even when the therapy can be guided by a companion diagnostic.

So getting beyond the hype of targeted therapies what have we learned (or perhaps re-discovered) now? Resistance to most targeted therapies emerges rapidly. Feedback loops and redundancy are ubiquitous. As a consequence blockade of a single molecular target is usually only partial. Primary tumours and their metastases exhibit much more molecular heterogeneity than previously acknowledged. The targeted agents themselves have led to the recognition that individual histological types of cancer are actually multiple different types of cancer when examined at the molecular level.

So what will Targeted Therapy 2.0 look like? Fundamentally the definition of the target is going to be redefined. The target will not not be just the molecule of interest – that will just be the starting point. The target will be the molecular pathway or the whole network of pathways that cluster around the molecule. Combinations of 2 or more 1st generation targeted therapies will be used to target a pathway at multiple points to overcome redundancy or 2 or more agents will be used across a network of pathways to exploit synthetic lethality. Multiple Hallmarks of Cancer will be targeted simultaneously. Combinations of targeted therapies have been tried before but I think this was largely because this is what oncologists have always done – combine drugs together to see what happens.

The second aspect of Target Therapy 2.0 that will become prevalent is the use of repeated molecular characterization of the cancer before and after exposure to therapeutic agents. This might be through repeated conventional biopsies or analysis of circulating tumour cells.

What are the barriers? The biggest challenge from a clinical perspective will be toxicity and tolerance of combining these agents. The secondary challenge will be the cost of therapy in clinical practice. Both of these barriers could drive greater interest in interventions of large magnitude of effect and perhaps with the expectation of significant short term toxicity (a bit like how we use chemotherapy).

The cost of these therapies might also lead to more creative thinking about the use of surgical therapy and adjuvant immunotherapy to minimise the need for non-immunological targeted therapies.

So it is now time for Targeted Therapy 2.0.

Andris Nelsons has put on his first series of nights with the BSO ahead of his 2014 appointment as Music Director.

Wagner – Siegfried Idyll

Mozart – Piano Concerto No 25 in C, K.503, with Paul Lewis on Piano.

Brahms – Symphony No.3 in F, op.90

Interestingly the hall has fantastic acoustics for the audience (from the orchestra) but the sound of the audience is strangely muted despite the standing ovation. The conductor is one of the new young guns…..certainly a lively performance but I just had the slightest feeling that he was slightly ahead of the orchestra, or the orchestra was slightly behind…..nonetheless the Brahms is a lovely piece.

Maurice Ravel – Daphnis et Chloe – Chorus of the Royal Opera House, Covent Garden & the London Symphony Orchestra under the direction of Pierre Monteux

Edward Elgar – Variations on an Original Theme op.36 – Enigma

Jacques Ibert – Divertissement – Paris Conservatoire Orchestra under direction of Jean Martinon

Camille Saint-Saens – Danse Macabre op.40

Georges Bizet – Jeux d’enfants op.22

Camille Saint-Saens – – Le Rouet d’Omphale op.31

Alexander Borodin Symphony No.2 in B minor with the London Symphony Orchestra under Jean Martinon

Arvo Part Fratres for String Orchestra and Percussion Parvo Jarvi and the Estonian National Symphony ORchestra