As many of you know, I’m a haematologist and oncologist; most of my work is in liquid tumours such as leukaemias and lymphomas. I was asked to start off this session in part to give some context to why is this meeting different, what is different about what we’re hearing today and how this will and may contribute to advances in cancer therapy in the next ten years. So really my talk is not going to be a scientific presentation, I was asked to give a historical context and that dovetails very powerfully with some of the presentations that will follow.

I began my talk in the main session by reminding us of a book that was particularly inspiring to me because it set the historical context for my medical studies and training and that was published in 1983 by Lew Thomas, a book called The Youngest Science: Notes of a Medicine-Watcher. When I first read that book I thought that perhaps a more appropriate title would have been The Adolescent Science because Thomas’ book was like an intimate portrait of a young discipline coming into maturity, the growing up story of medicine. The astonishing feature for Thomas in that book was the idea that physicians could use information about pathophysiology, the physiology of pathology, to construct and build observation upon observation, a new kind of medicine that was based on rational precepts. And to go on from there to mount genuine therapeutic interventions against diseases based on these precepts. So, for instance, once heart failure is reconceived in terms of pump dysfunction and volume overload you can imagine a therapy, albeit crude, that Thomas’ generation learned to use which is to take the volume away, in that case by removing a few pints of blood from the veins. They would actually have to go in there and pull out several pints of blood from heart failure patients; now we use, of course, a variety of sophisticated medicines to achieve the same kind of volume reduction effect, as many of you know. Similarly, once you had reconceived the recovery from streptococcal infection, which was a raging problem, as the serial deployment of various aspects of a host immunological response you could start creating a new therapeutic approach to it. In Thomas’ time they would actually inject a post-convalescent serum from a person who had already suffered and recovered from streptococcal septicaemia, they would inject that serum into a suffering patient. We now know that that strategy can be used for immunological defence, vaccination and immune response in general.

So why I am telling you this is that I think that cancer and medicine, at this ASCO and subsequent meetings, is entering its own period of adolescence. For the first time in our history we’re beginning to shrug off what many of us would recognise as the growing pains of the 1980s and some growing pains of the 1990s and hoping to learn to treat and prevent cancer potentially based on a few rational precepts. I’m often asked what’s happened in cancer medicine in the last decade or so, since the time Emperor of Maladies came out and also Ken Burns and I did the documentary for PBS. It seems to me that those can be distilled into three arenas and this is the set-up for the conversation today. Number one, targeting a cancer’s unique vulnerabilities, particularly in combination, yields successes for some but not all cancers. Number two, targeting a cancer’s microenvironment, for instance the immune microenvironment, is possible and effective in some cancers. And, number three, early therapy including definitive local therapy is generally more effective than late therapy. These are three principles that strike out to me as powerful new ideas. I won’t mention the actual trials involved but, for instance, I’ll just give you a couple of hints. We knew, we began to know about this, in the use of Herceptin for HER2 positive breast cancer. There you have a genetically annotated cancer and the use of a targeted therapy for a genetically annotated cancer. What falls out from those initial trials are two principles: number one, as I just said to you, the appropriate genetic annotation followed by the appropriate therapy for that annotated cancer is effective. This was an idea that was very novel in the world of cancer and has subsequently been shown to be true for several cancers.

But the second idea which was very important from those initial trials is that when you use that same medicine in a patient in whom all the visible tumour has been removed, in other words in the adjuvant setting, you also get powerful gains in survival, five and potentially ten year survival, from those trials. So another example in which the use of a therapy in an early setting, not in the diffusely metastatic setting but in the early setting, where the use of a targeted therapy was very effective. Haematologists knew this from the haematological world because in a disease like CML, chronic myelogenous leukaemia, Gleevec works extremely effectively as many of you know, imatinib or Gleevec works extremely effectively in the chronic phase of the disease. The same drug in the acute or blastic phase of the disease is much less effective. So this idea that targeted therapy has to be used at the appropriate time for the appropriate setting of a tumour is something that I think will recur many, many times in the future of cancer medicine. That’s an idea that I think we’ll return to many, many times.

In other words, if I was to generalise this principle it would lead to what I think might be the growing up experiment across cancers. That growing experiment can be summarised as following: early detection plus deep personalisation plus targeted therapy, possibly in combination. One interesting idea behind that is that we are now building into that grand experiment the idea of maintenance and surveillance so that a patient who has finished this one cycle, say, returns back in a full circle to maintenance and surveillance to detect relapse of cancer, the arrival, unfortunately, of a second or new malignancy in the context of the first or old malignancy and how to distinguish those two features from each other remains a new idea. So, again, to reconceptualise it, early detection plus deep personalisation plus targeted therapy followed by personalised or precision maintenance and surveillance is an idea that we will come back to many times.

It’s fair to say that people assembled here have some version of this formula or a roadmap formula for what might apply broadly to cancers. We can certainly argue about what your formula is versus my formula but I want to return back to that moment that I described for Lew Thomas in the 1940s which is to say that the central convergent idea here is that we as a community are learning to use rational precepts learned from cancer over the last decade and deploy them in human beings in a way that’s thoughtful, reasoned, compassionate and hopefully has bring seminal successes.

I will spend the second part of my talk though talking about a related idea which is the view that I just gave you is the physician scientist oncologist centric view of the world. I want to spend the second part talking about what it feels like to be a patient in this universe where the media is talking about this adolescence of cancer medicine, the moment in which we begin to deploy rational therapeutics for cancer, maintain, survey etc. I want to tell you the case of a friend of mine, Will Kiersky, a thirty-something journalist in New York. Eight years ago his mother took a photograph which I showed in the main talk of a healthy vigorous young man at a friend’s wedding. Last year he was diagnosed with a terrifyingly aggressive malignant melanoma which had spread to the lymph node in his left cheek. So he underwent treatment of immunotherapy and had a very brisk response, was maintained in the brisk response for a while, there was surveillance that was performed but then, unfortunately, he had a relapse about 12½ months after. He is currently on trial with a secondary trial at MSK with another targeted therapy and another version of immunotherapy. 

Here’s the point. In the picture that I picked up from eight years ago I can immediately spot the culprit lesion, there’s a little black mark on his cheek which would be the culprit lesion for the malignant melanoma. It turns out that I would be absolutely wrong; the actual culprit, it turns out, was a much smaller lesion which is much closer to his hairline and to the human eye these two things look absolutely identical. You could argue one way or the other. We don’t know why one of those lesions did not become the source of the melanoma but the other one did. Mavens of early detection, people who work on early detection, remember the formula that I talked about – early detection plus personalisation, deep personalisation, plus targeted treatment. So we hear and I had the opportunity to spend time investigating for a piece that I did for The New Yorker on deep learning algorithms that will pick up lesions such as the ones that this patient had and classify them as malignant versus non-malignant using criteria that clearly, based on a Nature paper, defy the most acute human eye, including seasoned pathologists. One of the pioneers of this idea I describe in this piece for The New Yorker envisages a world in which we are under constant diagnostic surveillance. For instance, a bath tub would perform sequential scans as you bathe via harmless ultrasound or magnetic resonance to determine whether there’s a new mass in an ovary or a pancreas. Big data thus watches and records and evaluates you and you shuttle from one algorithm to the next. The problem, as we all know in the world of cancer from prior experience, is that it sounds impressive but there’s a catch which is, again, I give you the example of that one mole which is completely self-contained whereas the other one spins out into a melanoma. Some cancers are designed to be self-limited, some cancers are designed not to be self-limited and we have done, so far, a heroic attempt at trying to understand which cancers we will die with and which cancers we will die of but that has been a huge project but that black box remains still to be opened.

Now think about the perspective of this patient. If a tumour was detected with this early detection paradigm this patient enters a kind of new cosmos. There’s the issue of over-diagnosis and over-treatment but then the question is should this patient be treated with some kind of therapy, an adjuvant therapy, once that mole is removed. Is it going to be a targeted therapy? Who is going to monitor that therapy? How are we going to pay for it? How are we going to run a trial and what the endpoints of that trial, what kind of surveillance do we have?

In the 1950s the sociologist Erving Goffman wrote a remarkable article about the concept of a total institution. ‘A total institution,’ Goffman wrote, ‘is one where a great number of similarly situated people cut off from the wider community for a considerable time together lead an enclosed formally administered round of life. Such total institutions have rituals of entry and exit; they inculcate belonging; they invent their own vocabulary and codes of behaviour; they have an internal logic which might be impenetrable to outsiders of the institution. They encourage surveillance and create anxiety; members are united by a common sense of purpose, by the feeling of being chosen, by the feeling of being marked. Those who are expelled from the institution feel a sense of betrayal and those who remain can be consumed by the privilege and guilt of survivorship.’ I’ve chosen these words very carefully because I do think for patients, especially as we move into the adolescence of cancer, cancer runs a risk of becoming such a total institution. This has been discussed before in the literature; in Solzhenitsyn’s Cancer Ward you had the example of a young man, Rusanov, who discovers he has a tumour in his neck and is whisked off to a kind of medical gulag which assumes total control of his actions. It’s a state he describes as more invasive and paralysing than the political state that he left behind. The poet Jason Shinder once wrote that, ‘Cancer is an opportunity to have your face pressed up against the glass of your mortality,’ but what patients see is not the glass, through the glass is not a world outside cancer but an internal reflection, cancer reflected endlessly around them like a hall of mirrors.

In this new era of cancer treatment which I am incredibly enthusiastic about, don’t get me wrong, I wonder if we are unwittingly but also insidiously intensifying the totality of the cancer institution for patients. For patients such as Will Kiersky for whom they have begun to describe this as a cancer world – they enter it, they remain in surveillance, they move from trial to trial. This world has them either in treatment, remission, surveillance, maintenance or re-surveillance, often for life. This world has created its own chilling vocabulary, the word ‘previvor’, pre-survivor, a word that refers to a person living with a cancer that has not yet occurred or yet relapsed. The idea, one patient described it to me as ‘No exit chemo,’ to describe the fact that a unique personalised chemo regimen for a patient, because of precision medicine, produces unique personalised toxicities. That phrase is borrowed from a Sartre novel in which every human being is assigned his or her own personal hell.

So let me be clear about one thing, I suspect like most people here I’m nothing less than enthusiastic about this new era of cancer therapy. I want it to work, I want it to work for my patients, for my children and for myself. But as we lunge forward into this cosmos of personalised genetic risk assessment, personalised surveillance, early detection potentially through machine learning, targeted therapy, immune therapy, maintenance and surveillance, I think we need to pause for a moment what it feels to be like a patient at the edge of this grand experiment. I wanted to leave you as we launch into a discussion of all of this with an image that was actually done three years ago from the documentary that I did with Ken Burns. This is Dr Lori Wilson, she’s a professor and a breast cancer surgeon who ironically was diagnosed with breast cancer herself at age 42. Her case is very unusual because she had cancer not in just one breast but two independent and genetically non-identical cancer in two breasts. So she underwent bilateral mastectomies and underwent chemotherapy. Ken Burns and I will also make The Gene: an intimate history into a PBS documentary and we will return to Lori Wilson’s case because now her tumour is being genetically annotated. She will enter the same kind of cycle of annotation, maintenance, surveillance potentially as we imagine using precision diagnostic tools to screen her after initial surgery and we try to imagine therapies that will diminish her chance of relapse. So Lori Wilson is at the edge of this grand experiment and her own stake in this process is so consequential and so enormous and personal that really words fail to describe it.

It falls on us to shepherd or parent the adolescence of cancer medicine as if it were the adolescence of our own children. We have to perform this experiment, and we should really call it an experiment, with the deepest possible integrity; to have the honesty to describe its results accurately; to have the moral clarity to invoke palliative and supportive care before subjecting patients to false hope and needless bodily harm; to have the enthusiasm and courage to carry it through; to have the will, should it succeed, to allow the poor and defenceless to access it less we divide the world into the rich who can afford personalised medicine and the poor who cannot. Finally, to have the fortitude, should it fail, to move on to yet another new way of thinking about cancer treatment and the future.