RESUMEN
BACKGROUND: Salvage radiotherapy (RT) (± androgen deprivation therapy (ADT)) is often used as a treatment in patients with biochemical recurrence (BCR) following radical prostatectomy (RP). Unfortunately, even after RT ± ADT, a significant number of patients will develop 'second' BCR. The aim of this study was to investigate the impact of postoperative treatments (adjuvant/salvage radiotherapy (RT) ± androgen deprivation therapy) on the recurrence pattern in patients with BCR following RP assessed by 11C-Choline PET/CT or 68 Ga-PSMA PET/CT. METHODS: Patients who developed BCR following RP and who had at least one positive lesion on PET/CT were retrospectively assessed. Positive spots were mapped as local, lymph node (LN), skeletal or visceral recurrence. A distinction was made between locoregional (prostate bed and pelvic LN) and extrapelvic recurrence (skeletal, visceral and/or extrapelvic LN). Patients were categorized according to postoperative treatment received in three subgroups (RT, ADT and RT + ADT) and compared with the reference group (RP only). The impact of the radiation field was also investigated. RESULTS: We identified 200 patients assessed by 68Ga-PSMA-11 (80%) or 11C-Choline PET/CT (20%). Patients who received postoperative RT + ADT had less LN recurrence distal to the common iliac bifurcation (26.7% vs 66.6%; p = 0.0004), but more recurrence to retroperitoneal LN than the reference group (38% vs. 14.4%, p = 0.02). Moreover, the RT + ADT subgroup had more extrapelvic recurrence compared to the reference group (66.2% vs 40.8%, p = 0.02). Patients who received RT to the prostate bed had more recurrence distal to the common iliac bifurcation compared to those who received RT to the prostate bed + pelvic LN (51.6% vs 26.1%, p = 0.0069). CONCLUSION: Post-prostatectomy treatments (ADT and/or RT) and the postoperative radiation field (prostate bed vs. prostate bed + pelvis) have a significant impact on the recurrence pattern. This knowledge can help clinicians to counsel their patients on their chances of being eligible for (locoregional) metastasis-directed therapies.
Asunto(s)
Colina/análogos & derivados , Isótopos de Galio , Radioisótopos de Galio , Recurrencia Local de Neoplasia/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Prostatectomía , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/cirugía , Radiofármacos , Anciano , Terapia Combinada , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/terapia , Antígeno Prostático Específico/sangre , Prostatectomía/métodos , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/terapia , Estudios RetrospectivosRESUMEN
There is substantial evidence that the endocannabinoid system and in particular the type 1 cannabinoid receptor (CB1R) is involved in epilepsy. We evaluated the in vivo effect of chronic administration of the anti-epileptic drugs valproate (VPA) and levetiracetam (LEV) on rat brain CB1 receptors using the positron emission tomography (PET) tracer [(18)F]MK-9470. Six Wistar rats were treated with VPA (200mg/kg) or LEV (50mg/kg) IP daily for 2 weeks. Dynamic imaging after intravenous injection of 18 MBq [(18)F]MK-9470 was performed on a FOCUS 220 microPET at baseline and after chronic treatment. Six animals were used as controls and were injected with saline, using the same protocol. Parametric images based on standardized uptake values (SUV) were generated and were spatially normalized to Paxinos space. These CB1R images were analyzed using a predefined volume of interest (VOI)-based analysis. Differences in SUV values between chronic and baseline scans in each condition (saline, VPA and LEV treatment) were calculated in each VOI. Direct binding affinity of the drugs at CB1R was assessed by competitive binding assay in Chinese hamster ovarian cells expressing human CB1R. Chronic injections of saline did not produce significant changes in global [(18)F]MK-9470 binding (p=0.43), nor in tracer binding in individual VOIs. We found a significant increase in global cerebral [(18)F]MK-9470 binding after chronic VPA administration compared to sham treated animals (+32.5%, p<0.001), as well as in tracer binding in all individual VOIs. After chronic administration of LEV, there was no significant change in global cerebral CB1R binding (+6.9%, p=0.81), nor in tracer binding in individual VOIs. As VPA does not exhibit high affinity for CB1R (displacement of [(3)H]-SR141716A 1.3+/-14.0%), such upregulation is most likely caused by an indirect effect on the endocannabinoid system. This increase in CB1R tracer binding and possibly signaling may represent a supplementary and new mechanism of VPA, but not LEV, since activation of CB1Rs has been shown to decrease excitability and excitotoxicity on-demand.