Cancer cells look like normal cells, although they proliferate in an uncontrollable manner. It is precisely because of this appearance that our immune system is sometimes unable to detect them. This means that our body does not generate an inflammatory response against these cells, as it would do for any other type of foreign agent. This means that, in the early stages, many tumours are invisible and painless. Pancreatic cancer is one that goes particularly unnoticed. This cancer proliferates without leaving a mark, and often, when it is detected, it is already at an advanced stage. It is the third most lethal type of cancer, both in Spain and across the world, and it looks likely to become the second most common cause of death from cancer in the next decade. Despite advances in diagnosis and new treatments, the global five-year survival rate is 9%.
8,300 patients are diagnosed with pancreatic cancer in Spain every year, with 1,300 of these patients living in Catalonia. Surgery is only possible in approximately 20% of the cases. In 40% of the cases, the cancer has already spread to other parts of the body via metastasis by the time of diagnosis. The tumour is localised in the remaining 40%, but it is a locally advanced stage due to the damage caused to arteries and veins. Locally advanced adenocarcinomas are inoperable with traditional techniques, with palliative chemotherapy being the only course of treatment until now. A multi-disciplinary assessment of the patient is essential at this early stage, which requires the collaboration of surgeons, oncologists, radiologists and anatomopathologists specialising in pancreatic tumours.
“The aim of the Multidisciplinary Pancreatic Cancer Committee of Vall d'Hebron University Hospital is for experts from different fields to study each patient on a case-by-case basis”, said Dr Joaquim Balsells, clinical director of the Pancreatic Surgery Unit of the Vall d’Hebron Hepatobiliopancreatic Surgery and Transplants Department and investigator of the Digestive and Liver Diseases Area of the Vall d’Hebron Research Institute (VHIR). The Committee is comprised of professionals from the Hepatobiliopancreatic Surgery and Transplants Department; the Medical Oncology Department; the Digestive Endoscopy Department; the Gastroenterology and Digestive Tract Department; the Radiology Department; the Interventional Radiology Department; the Pathological Anatomy Department; and the Nutrition and Radiation Oncology Department. Together, they reach a decision on the best therapeutic option for each individual patient, be they at an operable (locally advanced) or non-operable (metastatic) stage.
Between January 2019 and July 2021, the Multidisciplinary Pancreatic Cancer Committee conducted 686 evaluations on a total of 305 patients. “Between 50 and 60% of these patients sought a second opinion”, said Dr Elizabeth Pando, assistant physician in the Pancreatic Surgery Unit of the Hepatobiliopancreatic Surgery and Transplants Department and researcher in the VHIR's Digestive and Liver Diseases Area. “40% of the patients were enrolled in a clinical trial and 30% underwent surgery”, added Dr Teresa Macarulla, head of the Gastrointestinal Cancer Unit of the Medical Oncology Department at Vall d'Hebron University Hospital and principal investigator of the Gastrointestinal and Endocrine Tumours Group at the Vall d’Hebron Institute of Oncology (VHIO).
It is important to adopt a multidisciplinary approach when dealing with locally advanced pancreatic cancers. "No opportunity to control the disease beyond systemic chemotherapy should be ruled out", said Dr Pando. “For selected cases that are stable or showing a response to systemic treatment, we can consider enrolment in phase III clinical trials, personalised treatments or, in the best of diagnoses, the surgical removal of the tumour using advanced techniques such as complex vascular resections. We could also use complementary treatments within a clinical trial, such as radiofrequency treatments (or radiotherapy in unresectable cases) or other clinical trial options in the event of tumour progression”, she added.
Unlike other tumours, this cancer is particularly difficult to treat because it is hidden within the stroma, a fibrous tissue that protects and feeds the tumour cells, which makes it difficult for drugs to enter. This tissue also has immunosuppressive cells which block the entry of cells from the immune system that protect the body against malignant agents. “One of our challenges is to develop new techniques to break through this shield and reach the tumour”, said Dr Macarulla.
Faith in research
Research is a key aspect of the Multidisciplinary Pancreatic Cancer Committee. In cases where the patient cannot benefit from any of the available approved treatments, the Committee evaluates whether or not they could benefit from a drug at the trial stage. This will then be passed on to a specific Task Force coordinated by the Vall d’Hebron Institute of Oncology. As explained by Dr Elisabeth Pando, “clinical trials open the door to novel therapeutic strategies for one of the most aggressive tumours”. Collaboration on the Vall d’Hebron Campus between Vall d'Hebron University Hospital, the Vall d'Hebron Research Institute (VHIR) and the Vall d’Hebron Institute of Oncology (VHIO) enables a translational research, which is one that has a direct application and benefit for patients. “Some key agents in this process are the Molecular Therapy Cancer Research Unit (UITM)-CaixaResearch, the Molecular Pre-Screening Programme and the Cancer Genomics Group. These are all led by the VHIO and are benchmarks for the study of tumour genomics”, said Dr Helena Verdaguer, assistant physician in the Medical Oncology Department and investigator at the Vall d’Hebron Institute of Oncology (VHIO). Vall d’Hebron is thus a centre that brings together a broad range of high-quality research activity and healthcare treatments for pancreatic cancer patients.
One of the main clinical trials involving the participation of this multidisciplinary team is the PELICAN trial, which seeks to treat a locally advanced pancreatic adenocarcinoma through the use of a pioneering intraoperative radiofrequency surgery. . "With this technique, the needle breaks through the stroma and allows for the direct application of 80-degree temperatures to the tumour site. “These temperatures burn the tumour and kill the malignant cells, which helps to reduce the tumour volume and stimulate the immune response", explained Dr Pando. So far, 27 patients have been assessed as possible candidates for this treatment: “This is a unique study, because there has never been a phase III trial that compares an ablative technique with chemotherapy with chemotherapy alone”, explained Doctor Pando. The Multidisciplinary Pancreatic Cancer Committee has enrolled 11 patients in this clinical trial, which seeks to improve the prognosis of this tumour. None of these patients had complications during surgery. The study is ongoing and is expected to be completed in December. “If we confirm that this therapy can offer benefits for patients with advanced pancreatic adenocarcinomas, we may have a technique that improves the prognosis for this kind of tumour”, she explained.
Another example of the important research being carried out by this Committee is the phase II COMBAT trial, which opens the door to the treatment of pancreatic tumours with immunotherapy. A study has recently been published in the journal Nature, which has yielded promising results. “This is the first time that an immunotherapy has generated a response to this tumour”, explained Dr Teresa Macarulla, who is participating in this multi-centre study.
Vall d’Hebron University Hospital is the Spanish centre with the highest number of clinical trials currently ongoing for patients suffering from locally advanced pancreatic cancer.
Pancreatic cancer is a tumour that usually appears after 65 years of age. Cases are higher in elderly people and tend to occur more often in men. It is possible to reduce the risk of pancreatic cancer by leading a healthy lifestyle that involves regular exercise, balanced eating habits, low consumption of red meats and animal fats and the avoidance of alcohol and tobacco. Even so, in a percentage of cases there are germline genetic mutations that may predispose certain individuals to the development of this type of tumour at an earlier age.
