The best and most ruthless “sniper”, capable of recognizing and then killing a single enemy among thousands: it is radioligand therapy, a new frontier of oncology care and (ultra) precision medicine which promises to detect and eliminate even well-hidden single cancer cells. It is already applied on neuroendocrine tumors or Net but in the near future it could become an option for many cancers, revolutionizing the therapeutic approach for many patients. To make it known and above all to design a health organization that allows it to be used adequately and efficiently, the six scientific societies involved in the adoption of this clinical therapy have recently written the first “Multidisciplinary manifesto on radioligand therapy”.
First objective: to explain what the teragnostics, the principle on which this approach is based and which, as the name suggests, combines diagnosis and therapy: «It is about use radiopharmaceuticals in which the same molecule, called ligand or carrier, has a great affinity towards receptors expressed by the tumor cells, it is alternately “labeled” with two different radioactive isotopes », he explains Orazio Schillaci, president of the Italian Association of Nuclear Medicine and Molecular Imaging. «In a first step, the radiopharmaceutical that emits radiation detectable by diagnostic toolsby images such as PET, so as to precisely identify where cancer cells are located; in the therapeutic phase the radiopharmaceutical is administered composed of the same ligand and a radioactive isotope that equally selectively destroys the same cells in which it accumulates. In this way outbreaks of disease can be treated without damaging healthy tissues, expanding the possibilities of therapy for patients in whom the cancer has spread ».
The radiopharmaceutical therefore becomes a sniper, which recognizes and eliminates with aliterally millimeter accuracy the tumor, wherever it hides; an ability that can become fundamental in case of metastases or against neuroendocrine tumors in which the therapy with radioligand based on the Lutetium-17 isotope7 is already being used and has been shown to significantly improve survival. The advantage of radioligand therapy is the very high selectivity: the ligand only locks to its target therefore radioactivity acts only in a limited area and for limited periods, which depend on the decay time of the radioactivity itself, which is different for each radioisotope. Choosing the right target and the right radioisotopetherefore, the effect can be modulated by eliminating diseased cells without damaging nearby tissues, even when the tumor has spread to multiple sites and it is not possible to operate or treat it with systemic radiotherapy. The mechanism was recognized as innovative by Aifa. “The experience on rare cancers is invaluable in understanding how to manage a greater number of patients in the future: the goal is to focus on competence, with reference centers that deliver the therapy to which specialists in the area, who follow the patient closely , they can remotely access skills and information, creating a sort of “virtual” hospital, ”he says Massimo Falconi, president of the Italian Net Association.
Use in prostate cancer
90 percent of mortality in oncology depends on the appearance of metastasis and radioligand therapy can therefore prove to be a very effective option in these cases, as well as when the tumor is in hard-to-reach areas with surgery or “criticism” because if the scalpel damages the surrounding area, it can have serious consequences for the quality of life: just think of prostate cancer and the risk of injuring nerve structures due to continence and erection. Precisely this advanced or metastatic cancer is one of the possible ones new uses of radioligand therapy, as he explains Sergio Bracarda of the Italian Society of Oncological Urology: «Studies indicate that the approach offers a survival advantage in patients with metastatic prostate cancer which, like that of the breast, is dependent on hormones and therefore sees the modulation of androgen suppression as the main way of intervention: hormonal treatment is advantageous in terms of probability of success, but is limiting in terms of the possibility of treatment for those who develop resistances. Radioligand therapy, with its peculiar mechanism of action, offers one more option and it fits into a scenario very rich in therapeutic opportunities: it is therefore important to define the moment and situations in which it is most appropriate to use it ». Given the numbers of patients with prostate cancer, very different from those of patients with neuroendocrine tumors, an organizational effort will be required to ensure therapy for patients.
Other possibilities of use
The possibilities of use of radioligand therapy, however, do not end here: as well as enriching the range of weapons available at different stages of the evolution of the same tumor, because the molecular targets that each expresses change over time and a neoplasm that is initially unsuitable to be hit with a radioligand may become so, there are many neoplasms in which the use of “radioactive snipers” is being studied, from lymphomas to breast cancer, from melanoma to multiple myeloma, from lung cancer to pancreatic cancer. Observe Giordano Beretta, president of the Italian Association of Medical Oncology: «This strategy derives from iodine therapy 131, used for decades for thyroid cancer: now, with the new generation of radioligands, many opportunities open up for the diagnosis and treatment of other pathologies because these drugs allow to select and then treat patients with certain characteristics, that is, with sufficient receptor ‘targets’ that can be affected by the radioligand, thus increasing the efficacy and appropriateness of the treatment. To make this therapeutic innovation accessible to all patients who can benefit from it, however, their availability needs to be improved by overcoming administrative and organizational obstacles: interconnected oncological networks are and will be increasingly indispensable, allowing the patient, wherever he is, to access treatment in the most suitable place and closest to home ”, concludes Beretta.
The focus of radioligand therapy is the multidisciplinary team, because the cure can only be delivered bringing together many different specialist skills. As he explains Francesca Spada by Aiom “This does not mean sending the patient from one doctor to another or passing him to a reference center if you do not know how to intervene: the team is a group of specialists dedicated to a specific clinical context who discuss each case together in the first moment useful for diagnosis or in case of diagnostic suspicion, so on offer the patient the best path of diagnosis and treatment right from the start. Institutionalizing the process and the components of the teams is essential to prevent the patients from self-coordinating in the treatment path with negative clinical, emotional and economic consequences ».
A big organizational effort is needed
It’s hard to think of a more precise medicine than this: radioligand therapy literally is sewn on the individual patient, since its creation. Due to the decay times of radioactivity, well defined and linked to the nature of the radiopharmaceutical and the isotope used, the production and administration process is started from time to time for the individual patient through structured and rigorous organizational procedures in each step. Employment prospects are numerous, but in order for patients to really benefit from them, a small organizational revolution is needed, which keeps pace with innovation and also helps to go beyond worry that many feel just hearing about radioactivity and nuclear medicine. “The use of radioactive sources implies a careful evaluation of the safety for patients, operators and the general public,” he notes Michele Stasi, president of the Italian Association of Medical and Health Physics. “For example, we need to manage radioactive waste, protect doctors and operators with adequate paths and protocols, ensure the safety of family members and carers after dischargeThe medical physicist, who plays a central role in the patient’s radiation protection, takes care of all this. From 2020 there is also a novelty that opens up new scenarios for radioligand therapy: the European Directive 59/13 Euratom on radiation protection was in fact implemented by our country with the legislative decree 101/20 and allows to overcome the obligation of hospitalization in protected hospitalization for those treated with radiopharmaceuticals other than iodine 131. Evaluating for each radioactivity at the time of discharge and providing instructions to the patient and family members, it is possible to hypothesize the delivery of radioligand therapy on an outpatient or day hospital basis».
The census of the departments
A simplification, in compliance with safety, not insignificant given that being at the latest AIMN census in Italy the nuclear medicine departments where it is possible to provide this therapy are 254, but only 47 have protected hospital rooms, shielded for radiation, for a total of 220 beds: managing the sick without having to hospitalize them thanks to an adequate individual evaluation means being able to expand the audience of those who can access the treatment and therefore to be able to face the inevitable greater pressure on the departments when, in an increasingly near future, it will be possible to treat other neoplasms in addition to the Net (of the 2,700 new cases each year, 40-50 percent are indicated for radioligand treatment and this need is covered by the current ability to deliver care).
The role of medical physicist and radiopharmacist
However, the medical physicist, guarantor of radiation protection, is not the only specialist who will have to work alongside oncologist and nuclear doctor: the Manifesto also underlines the importance of the radiopharmacist, which, as he explains Monica Santimaria of the Italian Society of Hospital Pharmacy «It is the guarantor of the quality of care because it has to deal with the procurement of the radiopharmaceutical, its preparation in sterile environments, quality control, pharmacovigilance, clinical risk management, possible interactions with other drugs or foods. It therefore has transversal skills to all the specialized figures that revolve around radioligand therapy and can be their link “. As a demonstration of the fact that this approach works “in groups”: only with multidisciplinary teams and adequate structures will it really be possible to make this therapy available to all patients with indications for treatment.