Oligometastasis and local ablation in the era of systemic targeted and immunotherapy

Abstract

Background: During these last years, new agents have dramatically improved the survival of the metastatic patients. Oligometastases represent a continuous field of interest in which the integration of metastases-directed therapy and drugs could further improve the oncologic outcomes. Herein a narrative review is performed regarding the main rationale in combining immunotherapy and target therapies with SBRT looking at the available clinical data in case of oligometastatic NSCLC, Melanoma and Kidney cancer. Material and method: Narrative Review regarding retrospective and prospective studies published between January 2009 to November 2019 with at least 20 patients analyzed. Results: Concerning the combination between SBRT and Immunotherapy, the correct sequence of remains uncertain, and seems to be drug-dependent. The optimal patients' selection is crucial to expect substantial benefits to SBRT/ Immunotherapy combination and, among several factors. A potential field of interest is represented by the so-called oligoprogressed disease, in which SBRT could improve the long-term efficacy of the existing target therapy. Conclusions: A low tumor burden seems to be the most relevant, thus making the oligometastatic disease represent the ideal setting for the use of combination therapies with immunological drugs.

Dual mTOR/DNA-PK Inhibitor CC-115 Induces Cell Death in Melanoma Cells and Has Radiosensitizing Potential

“…Notably, brain metastases represent the main cause of death in melanoma patients [42]. Radiotherapy is frequently used to treat metastases, e.g., in the brain with stereotactic radiotherapy or bone with fraction regimens of 2 Gy up to a dose of 50 Gy [43][44][45][46][47]. Also, single symptomatic metastases can be irradiated if systemic treatment controls disease in the rest of the body.…”

Radiotherapy–Immunotherapy Combination: How Will We Bridge the Gap Between Pre-Clinical Promise and Effective Clinical Delivery?

“…In contrast, irradiating multiple lesions promoted promising effects when RT was combined with anti-PD-1 mAb in patients with a range of metastatic solid tumors [ 48 ]. Another report indicated that, in the context of oligometastases, ablative doses of RT together with IO agents improved the control rates of cancers including melanoma, NSCLC, and kidney cancer [ 49 ]. A study from Gomez et al supported the potentially curative approach of irradiating all lesions as standard of care for patients with oligometastatic NSCLC [ 50 ].…”

Immunothérapie et tumeurs oligométastatiques

“…Les résultats des combinaisons de RT à haute dose et d'immunothérapie ont récemment été publiés dans une revue narrative [31]. Dans le cadre du mélanome, seules des études rétrospectives sont présentées.…”

“…Les mêmes auteurs [31] ne sélectionnent que quelques cas cliniques intéressants de cancers du rein suggérant qu'immunothérapie et SBRT pourraient avoir un intérêt dans le contrôle tumoral. Une récente étude rétrospective incluant seulement 20 patients a regardé l'effet de la RT chez des patients traités par nivolumab, faisant la distinction entre SBRT à visée ablative (dose biologique équivalente (BED) > 50 Gy) pour des maladies oligoprogressives et RT à visée symptomatique [33].…”

“…La même étude de revue citée plus haut [31] a recensé 5 études rétrospectives incluant au total 178 patients. On note une hétérogénéité dans le nombre de métastases traitées par SBRT (1 à 10), le schéma de RT et la situation clinique (3 études concernant des maladies oligorécidivantes et 2 des cancers en oligoprogression).…”