It is a three times difficult tumor. Difficult to diagnose, because rare and “hidden”. Difficult to operate (in cases where it is possible to remove it surgically, i.e. more or less 25%). And difficult to treat. We are talking about pancreatic cancer, which affects around 15,000 people every year (6,800 men and 8,000 women, according to 2023 estimates), and which in over half of cases is discovered already at an advanced stage. For these reasons, the first message to pass on, perhaps the most important, is to direct patients to the reference centers – the Pancreas Units – if there is even just a suspicion of this tumor.
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Pancreatic cancer
The pancreas has an awkward anatomical position: it is in fact located between the stomach and the spinal column, and has an elongated shape in which it is possible to identify three parts: the “head”, in close contact with the duodenum, the central “body” and the “tail” is thin and extends up to the spleen. From a functional point of view it is made up of two types of tissue: the exocrine one which produces enzymes which contribute to digestion, and the endocrine one which produces hormones, including insulin and glucagon which regulate blood sugar levels.
There are different types of pancreatic cancer: the most aggressive is ductal adenocarcinoma, which is relatively rare and usually develops in the “head”, starting from the ducts that transport digestive enzymes. The average age of onset is between 60 and 70 years. Although pancreatic cancer currently represents only 3% of all diagnosed solid tumors, its incidence is growing and is expected to become the second leading cause of cancer death by 2030.
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Symptoms and diagnosis
“To make the diagnosis you need specific expertise – he explains Michele Reni, Director of the Strategic Clinical Coordination Program of the Pancreas Center at the IRCCS S. Raffaele Hospital in Milan – The risk of errors linked to the lack of specific expertise can be high and can complicate the picture of a disease which in itself evolves quickly ”. Unfortunately, the vague symptoms that may appear at the beginning do not help: burning, pain or heaviness in the stomach or back pain, common to very frequent pathologies, such as gastritis, ulcers and back pain. Difficult to focus attention on the pancreas. Some signs, however, can lead to suspicion: “Steatorrhea, i.e. a form of diarrhea which is often at the origin of various malabsorption syndromes; a thrombosis in the veins of a leg in the absence of another plausible explanation; or even unjustified weight loss, diabetes that suddenly appears in adulthood or already known diabetes that suddenly worsens. These are all conditions that should alert the doctor,” says the expert.
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How to treat it
As already mentioned, only in approximately one in 4 cases can surgery be resorted to. For all the others (20% discovered in the locally advanced phase and 50-60% in the metastatic phase) the treatment is based mainly on chemotherapies, which can now be combined in three different regimens. The drugs available are still few, they can be counted on the fingers of one hand, but there is some good news: the Italian Medicines Agency has recently approved the first drug for the second line of treatment of the metastatic phase, irinotecan pegylated nanoliposomal (Nal-IRI). It is not a target therapy but, thanks to nanotechnology, it manages to reach tumor cells in a targeted way. The lipid vesicles (liposomes) which contain the active ingredient (irinotecan) and which accumulate preferentially in the tumor act as carriers. Here the macrophages absorb the liposomes, releasing the irinotecan, which thus reaches the nucleus of the cancer cells, blocking their replication. This innovation is important, because the pancreas is surrounded by very dense connective tissue (the stroma) which hinders the passage of drugs administered through the normal systemic route.
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The effectiveness of the new Nal-IRI therapy was tested in the NAPOLI-1 pivotal study, where it demonstrated a 33% reduction in the risk of death in combination with two other drugs already used (5-fluorouracil and leucovorin). Thanks to a nominal use program, it was possible to use the drug in Italy before approval (between 2016 and 2018), and this made it possible to conduct a Real World Evidence study involving 11 oncology centers across the country national. “Having the drugs available before approval allows us to carry out academic research and deal with those aspects not investigated by the pharmaceutical company,” he explains Sara Lonardi, Director of Oncology 3 at the Veneto Oncology Institute. Data from approximately 100 cases were collected: the population was a little older and a little more complicated than that of the clinical study, but a reduction in the disease was observed in 12% of patients treated with Nal-IRI : “This is certainly not a negligible figure for this type of neoplasm – continues the oncologist -. Thanks to this treatment we are able to control the disease, stopping its progression for a period in 41% of patients. It may seem like little, but in the panorama of what we have today it is a small revolution and a great injection of hope: having a new drug available, in addition to providing a concrete benefit, means being able to say that we finally have something new for the treatment available for this type of tumor and that, for the majority of patients with advanced pancreatic cancer, it is now possible to extend survival while maintaining quality of life. And perhaps, in this time, new therapies could arrive. We have already seen this happen in oncology. Not only that: delaying the progression of the disease also means delaying the onset of new symptoms, especially pain and weight loss.” Last February, in the USA, Nal-IRI was approved as the first line of treatment.
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Brca-mutated pancreatic tumors
A separate discussion must be made for pancreatic tumors linked to mutations in the BRCA genes, which represent approximately 8% of cases in the Italian population. “Brca 1 and Brca2 are two genes that predispose to the development of tumors when they are defective, in the case of the pancreas we are talking above all about Brca 2 mutations,” underlines Reni. In general, targeted drugs of the PARP inhibitor class, such as olaparib, have proven effective for Brca-mutated tumors, but they have not been approved in Italy for pancreatic adenocarcinoma (although they are approved for ovarian tumors, of the breast and prostate): “With the lack of reimbursement of olaparib – continues Reni – we have lost the opportunity to raise awareness and reach out to oncologists and general practitioners in a widespread way to underline the importance of the genetic test. Which is not so much linked to the use of the drug, but to the possibility of identifying families in which the mutations are present and, therefore, of saving lives thanks to screening. Doing the genetic test on the patient is a complex investigation from a technological point of view, because the BRCA genes are large. However, once a mutation is identified, it is no longer necessary to test the entire gene in family members: just search for that specific mutation.”
Knowing the mutational status is also important for other reasons: patients with Brca mutations are usually more sensitive to platinum-based chemotherapies and have a better prognosis if treated promptly. But today the genetic test is not prescribed because, experts reiterate, it is not possible to separate these aspects from the impossibility of prescribing the targeted drug.
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The risk factors
Pancreatic cancer risk factors are related to both lifestyle and concomitant pathologies. Among the former we find smoking (74% higher risk than non-smokers), high alcohol consumption (which is also the main cause of chronic pancreatitis, itself an independent risk factor) and obesity (with a 10% increase in risk for every 5 units of body mass index). A correlation has also been found between the consumption of red meat, processed meat, foods and drinks containing fructose and saturated fatty acids. A further factor is type 1 or 2 diabetes: those affected are twice as likely to develop pancreatic cancer compared to non-diabetic people.
The register for familiarity
Then there is the family history: pancreatic cancer is defined as familial (up to 10% of cases) when the diagnosis involves two or more first-degree relatives. Patients with family history (which is different from heredity) have a 9 times higher risk than the population without family history, and this risk increases 32 times if there are three or more first degree relatives. To monitor these families, the Pancreas Familial Tumor Registry promoted by the Italian Pancreas Study Association (Aisp) has existed in Italy since 2008: people with specific family characteristics (listed on the registry website) can enter the study and the surveillance and undergo certain tests, including an annual MRI in specialized centers.
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Le Pancreas Unit
But what is meant by specialized centers, or Pancreas Unit? Multidisciplinary units integrating oncology, surgery, radiology, echo-endoscopy, gastroenterology, genetics, pathology, radiotherapy, nutrition, psycho-oncology, palliative medicine and nursing sciences. And which have adequate technologies, competent staff and high treatment volumes. Unfortunately there are not many, nor are they well distributed throughout Italy. It must be said that Lombardy is to date the only Region to have formally identified the network of its Pancreas Units, divided into Hub centers and Spoke centres. Furthermore, from April the interventions will only be able to be carried out in the 11 recognized Hubs capable of ensuring the necessary expertise. The important thing – the experts reiterate – is to raise awareness that this disease exists, that in the presence of symptoms it must be suspected and that the patient must be referred to the Pancreas Unit”.
#Pancreatic #cancer #treated
– 2024-04-09 19:17:15
