Combined immunotherapy encompassing intratumoral poly-ICLC, dendritic-cell vaccination and radiotherapy in advanced cancer patients.

Background: Combination immunotherapy has the potential to achieve additive or synergistic effects. Combined local injections of dsRNA analogues (mimicking viral RNA) and repeated vaccinations with tumor-lysate loaded dendritic cells shows efficacy against colon cancer mouse models. In the context of immunotherapy, radiotherapy can exert beneficial abscopal effects. Patients and methods: In this two-cohort pilot phase I study, 15 advanced cancer patients received two 4-week cycles of four intradermal daily doses of monocyte-derived dendritic cells preloaded with autologous tumor lysate and matured for 24 h with poly-ICLC (Hiltonol), TNF-α and IFN-α. On days +8 and +10 of each cycle, patients received intratumoral image-guided 0.25 mg injections of the dsRNA-analogue Hiltonol. Cyclophosphamide 600 mg/m2 was administered 1 week before. Six patients received stereotactic ablative radiotherapy (SABR) on selected tumor lesions, including those injected with Hiltonol. Expression of 25 immune-relevant genes was sequentially monitored by RT-PCR on circulating peripheral blood mononuclear cell (PBMCs) and serum concentrations of a cytokine panel were sequentially determined before and during treatment. Pre- and post-treatment PBMC from patients achieving durable stable disease (SD) were studied by IFNγ ELISPOT-assays responding to tumor-lysate loaded DC and by TCRß sequencing. Results: Combined treatment was, safe and well tolerated. One heavily pretreated castration-resistant prostate cancer patient experienced a remarkable mixed abscopal response to SABR+ immunotherapy. No objective responses were observed, while nine patients presented SD (five of them in the six-patient radiotherapy cohort). Intratumoral Hiltonol increased IFN-ß and IFN-α mRNA in circulating PBMC. DC vaccination increased serum IL-12 and IL-1ß concentrations, especially in patients presenting SD. IFNγ-ELISPOT reactivity to tumor lysates was observed in two patients experiencing durable SD. Conclusions: This radio-immunotherapy combination strategy, aimed at resembling viral infection in tumor tissue in combination with a dendritic-cell vaccine and SABR, is safe and shows immune-associated activity and signs of preliminary clinical efficacy.

Dosis de radiación producida por los pacientes durante la incorporación del radiofármaco en las pruebas diagnósticas de medicina nuclear / Radiation dose produced by patients during radiopharmaceutical incorporation in nuclear medicine diagnostic procedures

Objetivos. Evaluar la dosis que pueden recibir los miembros del público debido al contacto con pacientes de medicina nuclear durante la incorporación del radiofármaco y compararla con la dosis impartida una vez finalizado el estudio, con el fin de establecer recomendaciones. Material y métodos. Se estudiaron 194 pacientes de forma prospectiva. Se midió la tasa de dosis H*(10) a 0,1; 0,5 y 1 m tras la administración del radiofármaco, antes de la imagen y finalizada la prueba diagnóstica. Se calcularon las dosis efectivas para diferentes circunstancias de contacto, mediante el percentil-95 (gammagrafías óseas) y el valor máximo (resto de los estudios). Resultados. La dosis máxima que recibe el paciente por compartir sala de espera con otro paciente, durante la incorporación del radiofármaco, es 0,59 mSv. Si acudiese a una consulta médica, a un restaurante o a una cafetería las dosis a terceros alcanzarían los 23, 43 y 22 μSv. Estas dosis se reducen en un factor 3 cuando dicha actividad tiene lugar una vez finalizada la prueba. En la mayoría de los estudios, el uso del transporte privado, frente al público, reduce la dosis en un factor superior a 6. Conclusiones. Durante la incorporación del radiofármaco se recomienda maximizar la distancia entre pacientes y hacer una distribución de los mismos en función del tipo de estudio. Debe fomentarse que los pacientes hagan uso del transporte privado frente al público. Dependiendo del número de pacientes de medicina nuclear por año que reciba un médico en su consulta, puede ser necesario aplicar restricciones (AU)

Objectives. The aim of this study was to assess the dose received by members of the public due to close contact with patients undergoing nuclear medicine procedures during radiopharmaceutical incorporation, and comparing it with the emitted radiation dose when the test was complete, in order to establish recommendations. Material and methods. A prospective study was conducted on 194 patients. H*(10) dose rates were measured at 0.1, 0.5, and 1.0 m after the radiopharmaceutical administration, before the image acquisition, and at the end of the nuclear medicine procedure. Effective dose for different close contact scenarios were calculated, according to 95th percentile value (bone scans) and the maximum value (remaining tests). Results. During the radiopharmaceutical incorporation, a person who stays with another injected patient in the same waiting room may receive up to 0.59 mSv. If the patient had a medical appointment, or went to a restaurant or a coffee shop, members of the public could receive 23, 43, and 22 μSv, respectively. After finishing the procedure, these doses are reduced by a factor 3. In most of the studies, the use of private instead of public transport may reduce the dose by more than a factor 6. Conclusion. It is recommended to increase the distance between the patients during the radiopharmaceutical incorporation and to distribute them according to the diagnostic procedure. Patients should be encouraged to use private instead of public transport. Depending on the number of nuclear medicine outpatients per year attended by a physician, it could be necessary to apply restrictions (AU)

Radiation dose produced by patients during radiopharmaceutical incorporation in nuclear medicine diagnostic procedures.

OBJECTIVES: The aim of this study was to assess the dose received by members of the public due to close contact with patients undergoing nuclear medicine procedures during radiopharmaceutical incorporation, and comparing it with the emitted radiation dose when the test was complete, in order to establish recommendations. MATERIAL AND METHODS: A prospective study was conducted on 194 patients. H*(10) dose rates were measured at 0.1, 0.5, and 1.0m after the radiopharmaceutical administration, before the image acquisition, and at the end of the nuclear medicine procedure. Effective dose for different close contact scenarios were calculated, according to 95th percentile value (bone scans) and the maximum value (remaining tests). RESULTS: During the radiopharmaceutical incorporation, a person who stays with another injected patient in the same waiting room may receive up to 0.59 mSv. If the patient had a medical appointment, or went to a restaurant or a coffee shop, members of the public could receive 23, 43, and 22 µSv, respectively. After finishing the procedure, these doses are reduced by a factor 3. In most of the studies, the use of private instead of public transport may reduce the dose by more than a factor 6. CONCLUSION: It is recommended to increase the distance between the patients during the radiopharmaceutical incorporation and to distribute them according to the diagnostic procedure. Patients should be encouraged to use private instead of public transport. Depending on the number of nuclear medicine outpatients per year attended by a physician, it could be necessary to apply restrictions.