Traitement antalgique des métastases osseuses douloureuses par radiothérapie interne vectorisée

The aim of this retrospective study was to evaluate the efficacy and the safety of Quadramet^® and Metastron^® in 76 patients with painful bone metastases. The analgesic response was evaluated at six weeks, three months and six months. Blood counts performed every week allowed an assessment of the toxicity. The internal radiotherapy reduced the pain in 60% of patients with a complete pain disappearance in 26% and a reduction of analgesic consumption in 67% of them. This study did not show any statistically significant difference between the two treatments. However, we demonstrated that patients with a relatively long survival (≥4 months) had a better analgesic response (73 against 29%, p = 0.0004). The patients with a less than four months survival and those with CIVD and liver metastasis had a higher risk of thrombopenia. This retrospective study suggests that these treatments should be given preferably to treat patients with a relatively long life expectancy and that the detection of subclinic CIVD and liver metastasis could help to avoid severe thrombopenia.     

La radiothérapie interne vectorisée par les analogues de la somatostatine,en pratique,en 2019

Somatostatin receptors are overexpressed in differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NET). Radiolabeled somatostatin analogs have been used for a few decades for imaging and more recently for peptide receptor radionuclide therapy (PRRT) in a theranostic approach. Medical access to PRRT has long been limited to a few European specialized medical centers despite promising results in large cohorts of patients. NETTER-1, a phase 3 randomized trial, has demonstrated a drastic improvement of midgut NET patients progression-free survival in PRRT arm as compared to somatostatin analogs, leading to marketing authorizations in USA and Europe. PRRT clinical availability is growing in France, with around 20 medical centers offering this innovative treatment for GEP-NET patients care in 2019. PPRT success-story should lead to improvements of radionuclide therapy developments, which will reshape our medical specialty to a more “clinically” practice. This review aims to detail PRRT in clinical practice in France in 2019, with emphasize on treatment indications, planning and practical aspects. Radioprotection aspects and future optimization perspectives will also be discussed.     

La radio-immunothérapie préciblée des tumeurs solides : une démarche pluridisciplinaire

No effective therapy is currently available for the management of patients with metastases of most solid tumors. Thus, pretargeted radioimmunotherapy approaches have been developed that have shown promises. One of these techniques uses bispecific monoclonal antibody and radiolabeled bivalent haptens injected sequentially. In two clinical trials, 29 patients with advanced, progressive medullary thyroid carcinoma, as documented by short serum calcitonin doubling times, received an anti-carcinoembryonic antigen x anti-diethylenetriamine pentaacetic acid (DTPA)–indium) bispecific monoclonal antibody, followed four to five days later by an ¹³¹I-labeled bivalent hapten. Overall survival was significantly longer in high-risk, treated patients than in high-risk, untreated patients (110 versus 61 months; P < 0.030). Forty-seven percent of patients, defined as biologic responders by a more than 100% increase in calcitonin doubling time, experienced significantly longer survival than non-responders (159 versus 109 months; P < 0.035) and untreated patients (159 versus 61 months; P < 0.010). Toxicity was mainly hematologic and related to bone/bone-marrow tumor spread. Various multidisciplinary aspects of this long-term endeavor that resulted in long-term disease stabilization and a significantly longer survival in high-risk patients are described and discussed with respect to future directions of research on pretargeted radioimmunotherapy.     

Traitement médical des tumeurs endocrines digestives

Gastroenteropancreatic neuroendocrine tumors constitute a highly heterogeneous group of tumors with very different prognoses. It is important to distinguish between the well-differentiated neuroendocrine tumors (carcinoid tumors affecting the gastrointestinal tract and pancreatic endocrine tumors), which generally progress slowly, and the poorly differentiated endocrine tumors, which are characterized by being aggressive and of rapid progression. The treatment of the poorly differentiated forms is essentially based on chemotherapy, although prognosis remains poor. The well-differentiated forms require a more complex approach – depending on the site of the primary tumor, staging, the resectability of the lesions, and disease spread – and should therefore be defined within a multidisciplinary setting. The treatment of choice remains surgical excision of the primary tumor and metastases. No additional treatment has been demonstrated to be effective. For functional tumors, symptomatic treatment with a somatostatin analog for carcinoid tumors or a protein pump inhibitor for gastrinoma must be started rapidly to reduce the complications related to hormone secretion. For metastatic disease or for tumors that are not amenable to complete resection, several options can be proposed: careful monitoring, chemoembolization of liver metastases, systemic chemotherapy, or enrollment in therapeutic protocols offering targeted therapies. Stepwise introduction of these various therapies prolongs survival, even in metastatic disease.     

18FDG et radiothérapie externe,le point de vue du radiothérapeute.: Application des techniques de fusion d’images à la radiothérapie des carcinomes bronchiques

The prognosis of patients with localized non-small-cell lung carcinoma and treated with radiation therapy remains poor. The three-dimensional conformational radiotherapy aims to increase the dose of radiation at the tumor volume to increase the local control, while sparing the healthy tissue neighborhood. The reduction of the safety margins and the irradiated volumes obliges to determine with most acute precision the exact tumor volume. However, the scanner alone is insufficient, particularly at the mediastinal level and at a distance. The positron emission tomography allows distinguishing a biological tumor volume. It helps to define the lung tumor volume, especially when the tumor is accompanied by atelectasis, and to recover the lymph node staging at the mediastinal level and at a distance. Even if the sensibility and the specificity are not 100 %, positron emission tomography now becomes essential before considering an escalation of thoracic radiation dose.     

Effets de la radiothérapie sur la fonction testiculaire de l'adulte

Radiation therapy plays a major role in the curative management of numerous neoplasms, such as Hodgkin's disease or testicular cancer. However, the adverse effects of low-dose radiation scattered to radiosensitive normal tissues adjacent to the radiation fields, such as the testes, have been recognized. Experimental studies performed on healthy volunteers showed that no lesion was detectable on sperm counts or testicular biopsies after single doses of less than 10 cGy. Oligospermia has been reported after 15 cGy and 100 cGy result in a 90% incidence of azoospermia. In the radiotherapy of cancer, fractionated regimens are used to increase the differential effect between normal and tumoral tissues. For the same dose, a fractionated radiation regimen results in a higher incidence and a longer period of azoospermia than a single dose irradiation. Fractionated doses of >50 cGy result in a 100% incidence of azoospermia. For doses up to 200 cGy, recovery occurs but normal sperm production remains uncertain. Although the recovery time can be very long (more than 10 years), there is a risk of definitive azoospermia after doses of >200 cGy. Spermatogonia are the most radio-sensitive cell type and their depletion after small irradiation doses explain the effect of radiotherapy on fertility. Clinical hypogonadism is very unfrequent in usual practice, what seems to prove a relative radio-resistance of the Leydig cells. However, functionals studies show that there is a rise in serum LH with increasing dose to the testes. A decrease in testosterone levels has been reported after high testicular doses.     

Radiothérapie interne vectorisée par 177Lu-PSMA-617 de l’adénocarcinome prostatique métastatique résistant à la castration : à propos d’un cas et revue de la littérature

The prostate-specific membrane antigen (PSMA) is a type II glycoprotein which is over-expressed in prostate cancer tissue, especially in high grade tumours, metastatic disease, as an effect of androgen-deprivation therapies and in castrate-resistant prostate cancer (CRPC). Recent studies about radioligand therapy using PSMA ligands labeled with lutetium-177 (¹⁷⁷Lu) in CRPC patients have suggested its interest as a third line of treatment after second generation anti-androgens and chemotherapy by taxane. We present the case of a CRPC patient who was treated by iterative radioligand therapy using PSMA-617 ligand labeled with ¹⁷⁷Lu. This case illustrates on the one hand the efficacy of the treatment, and on the other hand the fragility of the patients who are at an advanced stage of their disease. Then we present a short review of the literature on this topic, focusing on the published efficacy and tolerance of ¹⁷⁷Lu-PSMA radioligand therapy of CRPC patients.