esanum: During the congress, you held a seminar on metastatic colorectal cancer1, an important topic in your research. What were the most interesting novelties you shared with colleagues?
The most relevant news in this area concerns liver transplantation, which is now a treatment option for selected patients with metastatic colorectal cancer. This is an extremely important novelty, which results from the TransMet2 study. The French study, which also enrolled patients in Belgium and Italy, looked at patients who had received systemic chemotherapy treatment despite which they remained ineligible for radical surgical resection. Patients were randomised either to receive the standard of care or to undergo liver transplantation. The results show that those who underwent liver transplantation had important clinical advantages in terms of survival compared to those who continued only with systemic treatment.
I would like to point out that liver transplantation is not intended to cure patients of their cancerous disease, which must also be considered when weighing up the possible benefits and risks of major surgery. These patients, in most cases, have relapses, but, after the transplant, they only have relapses on the lung, which often makes subsequent targeted interventions possible. One example is stereotactic radiotherapy, which has kept more than a significant proportion of these patients disease-free five years after randomisation.
This is a treatment that has a very important impact on the life expectancy of patients with liver-limited disease that cannot be surgically resected even after chemotherapy. I believe that this study will not only change our clinical practice, but precisely change the way we think about organ transplantation in the history of treating cancer patients.
esanum: What are the selection criteria for nominating a patient with unresectable metastatic colorectal cancer for liver transplantation?
To date, selection could be based on the inclusion criteria of the TransMet study, the most robust evidence available. In the TransMet study, patients were enrolled who were less than 65 years old, in good general condition, whose disease had been stable for at least six months with medical treatment, and who were judged not to be candidates for surgical resection by a multidisciplinary board consisting also of several surgeons with expertise in the hepatobiliary field.
Liver transplantation in these patients does not replace surgical resection of liver metastases. This procedure remains the gold standard when it is technically feasible and oncologically sensible. Liver transplantation is only an alternative for a specific group of patients.
There are also molecular criteria that help in selecting patients. For example, the tumour must be BRAF wild-type (the presence of the mutation makes the disease extremely aggressive) and must not have mismatch repair deficiency (these tumours respond very well to immunotherapy). Also to be considered is the Oslo score which identified four negative predictors: maximum tumour size >5.5 cm, progressive disease on chemotherapy, interval from primary tumour resection to liver transplantation <24 months and pre-transplant carcinoembryonic antigen >80 μg/mL. If we were considering 100 patients with unresectable colon cancer, this treatment option would probably be offered to a maximum of 5-6 patients.
The selection of the optimal transplant candidate is therefore the key to the success of this possible therapeutic weapon. This is why, in my opinion, patient assessment cannot be done without a group of experts in the hepatobiliary field, both from an oncological and surgical point of view, as was done in the TransMet study. I believe that, in clinical practice, the individual case should be assessed by a national board, which would first and foremost decide whether the patient should undergo surgical resection of the liver metastases.
The selection of patients eligible for transplantation should not be done locally, perhaps in small centres with little expertise. This is no longer just a matter of spending money on medical treatment, but also of allocating an organ, a procedure that obviously involves ethical and social issues. Indeed, given the scarce availability of organs, the decision to subject a cancer patient to a liver transplant could compete with other indications, oncological or non-oncological.
esanum: Prevention diagnosis, therapy: where are the greatest strides being made when we talk about gastrointestinal oncology and why?
I believe that, from the concrete point of view of clinical application, the greatest steps forward are those relating to the molecular characterisation of tumours, having identified subgroups susceptible to certain treatments with a good chance of success. Today, we can direct therapeutic choices on the basis of characteristics studied on the individual tumour, a great achievement.
Think of colon cancer patients: there are subgroups defined by molecular characteristics, such as patients with mismatch repair deficiency, who respond very well to immunotherapy, or those with KRAS mutations that can be targeted for therapy. If molecular tests indicate that metastatic stomach cancer has an elevated level of HER2 (human epidermal growth factor receptor 2) or PD-L1 (programmed death-ligand 1), specific treatments could be offered for these tumour types. New targets under investigation for gastric and gastro-oesophageal junction carcinoma include Claudin.
Another important area of development concerns the implementation of liquid biopsy techniques in all phases of the approach to the cancer patient, first and foremost in diagnosis. There are more and more data showing that a blood sample will enable us to diagnose different types of cancer. Obviously, the levels of sensitivity and specificity will have to be absolute for this procedure to become part of clinical routine. With this procedure, we will also have higher levels of acceptance in the screening pathway than we have today (think of the poor compliance of patients when they are invited to be tested for faecal occult blood).
esanum: Several studies confirm that in recent decades, worldwide, the number of new cancer cases has increased significantly in people under the age of 50. What are the causes of this phenomenon?
One cause could be found in the increased awareness we have today with regard to familial and genetic diseases. This leads to a greater tendency to do screening tests in population groups with a high probability of having a family or genetic disease. Thus, of course, the likelihood of diagnosing the disease, often early, increases, which then has a positive impact on prognosis and mortality.
This does not completely explain the phenomenon, because there are many sporadic cases, whose disease is not familial or genetic, that emerge at a young age. Almost certainly many of these cases are linked to environmental oncogenic factors, which over time can lead to the development of a tumour. However, today, we do not have a demonstration of this causal link with a high level of evidence. There is a lot of literature on the subject, but we have not yet demonstrated a causal link with the disease. For example, the impact of microplastics absorbed through certain foods on human health is being studied.
There is also a lot of talk about the microbiota, the alteration of which, due to both environmental agents and pharmacological therapies, such as antibiotic therapies to which we are often exposed from the first months of our lives, seems to affect the onset of gastrointestinal cancers. Not to mention air pollution. However, today there is no clear evidence of which factors are influencing this, so it is difficult to make prevention recommendations to the population.
From my point of view, what we can do today, considering this increase in the incidence of cancer in younger patients, is, when possible, to increase the uptake of screening tests. Speaking for example of colon cancer, based on epidemiological trends, it makes good sense, in my opinion, to bring forward the start date of screening tests to 45 years of age compared to 50 today.
esanum: The role of biomarkers in the personalisation of cancer therapies is constantly growing. How do you assess the importance of these tools in the treatment of gastrointestinal cancer?
Biomarkers play an extremely important role in personalising therapeutic strategies in oncology. In the future, we will be able to analyse many biomarkers and orientate ourselves towards the best treatment for that particular patient.
Today, in gastroenteric cancers, with the exception of biliary tract cancer, we use few biomarkers to make therapeutic decisions. In clinical practice we need 'actionable' biomarkers, which are targets for drug therapy. In fact, the knowledge that there is a certain underlying mutation in a given tumour, without it being able to be used as a therapeutic target, is of little use. I am confident that, as research progresses, we will have more and more biomarkers available for personalising therapy, not only for metastatic disease, but also for early-stage disease.
This breakthrough would ensure not only a better rate of disease control, hence an increase in life expectancy without cure, but also, by characterising the tumour at an early stage, to target with therapy the alteration responsible for tumour growth, which is likely to result in a higher cure rate.
esanum: What are your views on the use of artificial intelligence and big data in gastroenterological cancer research?
I believe that today, the multiple applications of artificial intelligence in cancer treatment are essentially the prerogative of research. In this field, without artificial intelligence, it would be absolutely impossible to put together and analyse the huge amount of clinical, molecular, transcriptomic, radiomic, etc. data that we have at our disposal. Today, artificial intelligence for research purposes represents, in my view, a great glue that allows a global analysis and evaluation of all the elements that doctors have at their disposal today for the treatment of cancer patients. In the future, artificial intelligence will probably also be an important aid in clinical practice.
esanum: You are President of the North West Oncology Group (Italian: Gruppo Oncologico Nord Ovest or GONO): what impact is this foundation having on cancer research in Italy?
I believe that the activity of the GONO Foundation in our country is extremely important, not only for the support given to research projects and clinical studies that are useful for our patients, but also for the results obtained. GONO has conducted scientific studies that have led to changes in guidelines not only in our country, but also in European, US and Asian scientific societies.
In the field of research and clinical trials, GONO has given some patients access to liquid biopsy (not yet reimbursable by the National Health Service), both in the diagnosis of minimal residual disease, after surgery, and in the choice of treatment in metastatic disease. And it has given early access to some innovative drugs.
GONO's mission is to try to go beyond national borders and implement more and more projects in a European context. The main idea is to try to set up very practical, very pragmatic collaborations that will put us in step with the pace of independent European academic research, offering more and more cutting-edge possibilities for our patients.
esanum: 'Oncologist, researcher, mum of two monsters, fond of French fries and Coca Cola': this is your biography on X (formerly Twitter). Can you tell us more about reconciling being a mum with such a demanding profession? In 2024, unfortunately, the topic of gender integration is still relevant.
This is a topic that touches me closely. I have had an extremely happy, fortunate and rewarding professional life. Perhaps I have always been in the right place at the right time. I made consistent work choices, I always worked in a serene environment, with people who taught me how to work and grow. I became a full professor of oncology at the age of 39, so I think I should be truly grateful and happy for what I have been able to do professionally. Beyond the titles and awards, I think I have done a lot of good research, which makes me proud.
My professional career has not prevented me from dedicating myself to my family. I have a husband and two children, who are one of the greatest joys of my life. However, reconciling professional and family life has not been easy, and still is not. I could not have done any of what I have done without the practical help of my husband and my family of origin.
In my professional experience, I have never encountered obstacles in the working or academic environment, I have never been sidelined as a woman, I have never felt that I counted less than my male colleagues. What I have encountered is the absolute lack of services for families. Often, when we talk about gender issues and the integration of women, we lose sight of the practical side. There are not enough places in kindergartens, schools in summer close for 13 consecutive weeks, school meetings are organised at times that conflict with the needs of families where both parents work. These are concrete problems of everyday life, from which we have to start in order to do gender mainstreaming.
Gender integration, in my opinion, is done with concrete actions, not proclamations. Establishing, for example, a minimum percentage of women in a committee is useless if you do not allow women to participate concretely. I would like less proclamations and more pragmatism from institutions and companies. A woman who gives up work or engages in less demanding and less remunerative work because she has no services to support her family is, to me, a failure of society.
- Cremolini C. Treatment of MSS colon cancer first- line, maintenance: Current and future options, future. ESMO Gastrointestinal Cancers Congress 2024. 28/06/2024.
- Adam R, Badrudin D, Chiche L, Bucur P, Scatton O, Granger V, Ducreux M, Cillo U, Cauchy F, Lesurtel M, Mabrut JY, Verslype C, Coubeau L, Hardwigsen J, Boleslawski E, Muscari F, Jeddou H, Pezet D, Heyd B, Lucidi V, Geboes K, Lerut J, Majno P, Grimaldi L, Boukhedouni N, Piedvache C, Gelli M, Levi F, Lewin M. Safety and feasibility of chemotherapy followed by liver transplantation for patients with definitely unresectable colorectal liver metastases: insights from the TransMet randomised clinical trial. EClinicalMedicine. 2024 Apr 27;72:102608. doi: 10.1016/j.eclinm.2024.102608. PMID: 38721015; PMCID: PMC11077272.