Metabolic therapy and internal dosimetry: A difficult but necessary encounter

Estorch Cabrera, M.

doi:10.1016/j.remnie.2021.03.020

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(a) MIP of patient with MCC. In addition to the bone metastasis of the D9 vertebral body, a hypermetabolic pulmonary nodule was detected which was typed as a second primary tumor (lung adenocarcinoma) by histopathology. The findings led to a change in stage (from IIA to IV) and treatment (from observation to chemotherapy together with radiotherapy treatment for the bone metastasis). (b) MR of vertebral spine showing the metastatic D9 lesion showing increased intensity in the STIR sequence. (c) Axial PET slice showing the hypermetabolic right lung lesion (SUVmax 6.2). (d) Axial chest CT slice showing the 21mm pulmonary nodule." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "V. López Prior, B. Llombart Cussac" "autores" => array:2 [ 0 => array:2 [ "nombre" => "V." "apellidos" => "López Prior" ] 1 => array:2 [ "nombre" => "B." "apellidos" => "Llombart Cussac" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S2253654X20302171" "doi" => "10.1016/j.remn.2020.11.012" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2253654X20302171?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2253808921000641?idApp=UINPBA00004N" "url" => "/22538089/0000004000000003/v1_202104250727/S2253808921000641/v1_202104250727/en/main.assets" ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "Editorial" "titulo" => "Metabolic therapy and internal dosimetry: A difficult but necessary encounter" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "137" "paginaFinal" => "138" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "M. Estorch Cabrera" "autores" => array:1 [ 0 => array:3 [ "nombre" => "M." "apellidos" => "Estorch Cabrera" "email" => array:1 [ 0 => "mestorch@santpau.cat" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Presidenta del Grupo de trabajo de Endocrino de la SEMNIM" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Terapia metabólica y dosimetría interna: un encuentro difícil pero necesario" ] ] "textoCompleto" => "Metabolic therapy is a procedure that has been performed since the end of the fourth decade of the 20th century when the first treatment with 131I in a patient with thyroid cancer was published.<a class="elsevierStyleCrossRef" href="#bib0055">1</a> This therapy is based on the administration of a radiopharmaceutical to be incorporated by the lesion to treat and performing selective irradiation. Despite the demonstrated effectiveness of this treatment, over time it has necessarily and logically been redirected with the publication of guidelines that establish the time and the dose of the radioiodine to administer along the course of the disease. The dose is almost always empiric or fixed, since dosimetry calculation is “difficult and cumbersome” in clinical practice, with better results than with the fixed dose not having been demonstrated to date. Indeed, one of the limitations attributed to metabolic therapy is the absence of individual dosimetric studies for either the calculation of the activity to administer or for calculating the dose absorbed post-treatment. Taking this into account, it seems imperative to develop this field, even more so since the appearance of new forms of metabolic therapy beyond the classical treatment with 131I, and this is expected to be an area of expansion in the immediate future. Therefore, the biological effects of radiation should be examined in depth in order to understand the results of these therapies and thereby improve the accuracy of these treatments. Publication of the European Directive 2013/59/EURATOM, after the RD 601/2019 and, overall, the increasingly greater extension of the implementation of treatment with 177Lu-DOTATATE make it necessary for nuclear medicine physicians and radiophysicists to start working on this. The objective should be to implement a single standardized dosimetric procedure, which is technically within the reach of all the centers that perform metabolic therapy and is comfortable and feasible for the patients, and is, overall, useful and provided information of clinical interest.The objective of the Special Collaboration by Monserrat et al.<a class="elsevierStyleCrossRef" href="#bib0060">2</a> was aimed at describing the basic concepts of internal dosimetry and explain, according to their experience, its practical application in the treatment of neuroendocrine tumors treated with 177Lu-DOTATATE. However, no reference is made to the possibility of demonstrating the clinical utility of the method proposed. To achieve their objective, they divide the method to calculate the dose absorbed into three sections: quantification of the activity (as in the measurement of the activity of each of the regions that are the source of the activity), sampling of the activity and calculation of the activity–time curve (specifying the number of times and the time at which this activity is measured in each region of activity and how to obtain the activity–time curve) and calculation of the dose absorbed in each target region. To carry out the first section, the use of hybrid SPECT/CT equipment duly calibrated with SPECT with self-contouring and with an external probe that can be a gaseous detector (ionization chamber or Geiger-Müller) or a scintillation crystal and well counter. For the second section, they recommend three SPECT/CT acquisitions (which may be at 24h, 72h and 168h post-administration, although there is no agreement), the obtainment of at least 6 blood samples in the first 24h, and the recommendation of obtaining another between 24h and 168h and perform at least 6 whole body measures during the first week post-treatment (the first 3 or 4 before 24h). Finally, the numerical calculations are made to obtain the dose absorbed in each target region. In this section, the uncertainty of the calculations should be taken into account since “in a complete internal dosimetry count there are many sources of uncertainty to consider and detailed quantification of all of these uncertainties is a laborious process” (sic).Significant effort by nuclear medicine physicians and the radiophysicists is necessary to perform all of the above and requires an important length of time and equipment in addition to being a long and uncomfortable procedure for the patients. The objective of the nuclear medicine physician, assumed by the Endocrinology Working Group of SEMNIM, should be to identify what can be achieved with dosimetry and that what is achieved represents, overall, benefits for the patient. The radiophysicists propose a method, but what does the nuclear medicine physician need? How do we choose the target lesions in a patient with metastases (how many, which and at what time after treatment)? How do we relate the treatment to the clinical manifestations and the response (RECIST, PERCIST, etc.)? Is pretreatment dosimetry necessary? In addition, as the special medications that they are, radiopharmaceuticals are submitted to requisites established by the Law of Medications which determines the activity to administer in each treatment. Therefore, the objective of dosimetry in relation to the calculation of the dose to administer should not currently b the priority, and it would probably be more convenient to look for surrogate objectives of clinical interest which are shared and have consensus among nuclear medicine physicians. Finally, it should be accepted that the result of metabolic therapy in our patients (complex, with advanced cancer, resistant and in progression to previous therapeutic lines, also making up a very heterogeneous population…) is multifactorial, and the dose absorbed, regardless of the calculation method, is only one more factor, with close collaboration with all the professionals involved being essential.<a class="elsevierStyleCrossRef" href="#bib0065">3</a>At present, most studies published in the scientific literature as well as the clinical guidelines continue using fixed therapeutic doses for radiopharmaceuticals or doses calculated with respect to the weight of the patient, and this is especially evident in the treatment of differentiated thyroid cancer with radioiodine.<a class="elsevierStyleCrossRef" href="#bib0070">4</a> This fact probably indicates that metabolic therapy should not be focused as if it were a treatment with ionizing radiations of external application (read radiotherapy) but rather as the administration of a system treatment aimed at tumors independently of the tumoral load or the number of metastases (read chemotherapy). In addition, the radiobiological action of metabolic therapy at a cellular and molecular level should not be forgotten. At these levels the sensitivity at low doses presents an individual genetic variability. Neither can the associated clinical characteristics and variables inherent to each patient individually be put aside.<a class="elsevierStyleCrossRefs" href="#bib0075">5,6</a> For this reason it is imperative to demonstrate that dosimetry can be a quantitative procedure that provides additional clinical benefits to standard procedures.<a class="elsevierStyleCrossRef" href="#bib0085">7</a>Since the implementation of treatment with somatostatin analogs labeled with 177Lu or 90Y, numerous clinical and especially, experimental studies have aimed to find a method to perform adequate dosimetry, mainly renal dosimetry due to the nephrotoxic potential of this treatment.<a class="elsevierStyleCrossRef" href="#bib0090">8</a> However, despite this evidence, few centers perform dosimetry in their patients because the thresholds that allow avoiding toxicity in the organs at risk are not defined and improvement in efficacy in relation to tumoral response has not been shown.<a class="elsevierStyleCrossRef" href="#bib0095">9</a> Up to now, no dose calculation method has shown to be more effective than the scaling of doses in the initial phases of a clinical trial. While the community of nuclear medicine does not deny its interest in a single, dosimetric method that is available for all centers and also for all the patients who should be treated with not only 177Lu-DOTATE but also with other currently available radiopharmaceuticals, but there are still many questions which remain to be answered before we establish a method that can calculate the dose of a radiopharmaceutical that each patient should receive.<a class="elsevierStyleCrossRef" href="#bib0100">10</a>In conclusion, while dosimetry calculation in metabolic therapy is foreseen to be potentially useful for improving the effectiveness of this treatment, further randomized, prospective trials are needed to demonstrate its clinical benefits compared to the well-established current and safe methods based on the administration of empiric or fixed doses or on the calculation of the dose of the radiopharmaceutical to be administered according to the weight of the patient. With this objective, nuclear medicine physicians and radiophysicists should closely collaborate, and the latter should understand the multifactorial idiosyncrasy of the treatment with radiopharmaceuticals and the fragility of most patients undergoing this treatment." "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "⋆" "nota" => "Please cite this article as: Estorch Cabrera M. Terapia metabólica y dosimetría interna: un encuentro difícil pero necesario. 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ISSN: 2253-8089

The Revista Española de Medicina Nuclear e Imagen Molecular (Spanish Journal of Nuclear Medicine and Molecular Imaging), was founded in 1982, and is the official journal of the Spanish Society of Nuclear Medicine and Molecular Imaging, which has more than 700 members. The Journal, which publishes 6 regular issues per year, has the promotion of research and continuing education in all fields of Nuclear Medicine as its main aim. For this, its principal sections are Originals, Clinical Notes, Images of Interest, and Special Collaboration articles. The works may be submitted in Spanish or English and are subjected to a peer review process. In 2009, it became the leading Spanish journal in the field of Medical Imaging on having an Impact Factor , awarded by the Journal Citation Reports.

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