RESUMEN
The results of this survey reveal current clinical practice in the handling of combined radioimmunotherapy with Immune Checkpoint Inhibitors (RT + ICI). We aim to provide a basis to open a discussion for clinical application of RT + ICI by analyzation of experts' assessment. We conducted a survey with 24 items with a focus on side effects of RT + ICI, common practice of scheduling and handling of adverse events. After pilot testing by radiation oncology experts the link to the online survey was sent to all members of the German Society of Radiation Oncology (DEGRO). In total, 51 radiation oncologists completed the questionnaire. Pulmonary toxicity under RT + ICI with ICIs was reported most frequently. Consensus was observed for bone and soft tissue RT of the limbs in favor for no interruption of ICIs. For cranial RT half of the participants do not suspend ICIs during normofractionated radiotherapy (nfRT) or stereotactic hypofractionated RT (SRT). More participants pause ICIs for central than for peripheral thoracic region. Maintenance therapy with ICIs is mostly not interrupted prior to RT. For management of RT associated pneumonitis under durvalumab the majority of 86.3% suggest corticosteroid therapy and 76.5% would postpone the next cycle of ICI therapy. The here obtained assessment and experiences by radiation oncologists reveal a large variability in practical handling of combined RT + ICI. Until scientific evidence is available a discussion for current clinical application of RT + ICI should be triggered. Interdisciplinary consensus guidelines with practical recommendations are required.
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Actitud del Personal de Salud/etnología , Oncólogos de Radiación/psicología , Radioinmunoterapia/métodos , Adulto , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Competencia Clínica , Femenino , Alemania , Personal de Salud/psicología , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Radioinmunoterapia/efectos adversos , Radioinmunoterapia/tendencias , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
Radiotherapy is one of the most common modalities for the treatment of cancer. One of the most promising effects of radiotherapy is immunologic cell death and the release of danger alarms, which are known as damage-associated molecular patterns (DAMPs). DAMPs are able to trigger cancer cells and other cells within tumor microenvironment (TME), either for suppression or promotion of tumor growth. Heat shock proteins (HSPs) including HSP70 and HSP90, high mobility group box 1 (HMGB1), and adenosine triphosphate (ATP) and its metabolites such as adenosine are the most common danger alarms that are released after radiotherapy-induced immunologic cell death. Some DAMPs including adenosine is able to interact with both cancer cells as well as other cells in TME to promote tumor growth and resistance to radiotherapy. However, others are able to trigger anti-tumor immunity or both tumor suppressive and immunosuppressive mechanisms depending on affected cells. In this review, we explain the mechanisms behind the release of radiation-induced DAMPs, and its consequences on cells within tumor. Targeting of these mechanisms may be in favor of tumor control in combination with radiotherapy and radioimmunotherapy.
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Alarminas/metabolismo , Neoplasias/radioterapia , Radioinmunoterapia/métodos , Adenosina Trifosfato/metabolismo , Animales , Muerte Celular , Proteína HMGB1/metabolismo , Proteínas del Choque Térmico HSP72/metabolismo , Proteínas HSP90 de Choque Térmico/metabolismo , Humanos , Radioinmunoterapia/tendencias , Microambiente TumoralRESUMEN
PURPOSE OF REVIEW: Cancer is one of the leading causes of death and the incidence rates are constantly rising. The heterogeneity of tumors poses a big challenge for the treatment of the disease and natural antibodies additionally affect disease progression. The introduction of engineered mAbs for anticancer immunotherapies has substantially improved progression-free and overall survival of cancer patients, but little efforts have been made to exploit other antibody isotypes than IgG. RECENT FINDINGS: In order to improve these therapies, 'next-generation antibodies' were engineered to enhance a specific feature of classical antibodies and form a group of highly effective and precise therapy compounds. Advanced antibody approaches include among others antibody-drug conjugates, glyco-engineered and Fc-engineered antibodies, antibody fragments, radioimmunotherapy compounds, bispecific antibodies and alternative (non-IgG) immunoglobulin classes, especially IgE. SUMMARY: The current review describes solutions for the needs of next-generation antibody therapies through different approaches. Careful selection of the best-suited engineering methodology is a key factor in developing personalized, more specific and more efficient mAbs against cancer to improve the outcomes of cancer patients. We highlight here the large evidence of IgE exploiting a highly cytotoxic effector arm as potential next-generation anticancer immunotherapy.
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Antineoplásicos Inmunológicos/uso terapéutico , Oncología Médica/métodos , Neoplasias/tratamiento farmacológico , Medicina de Precisión/métodos , Radioinmunoterapia/métodos , Anticuerpos Biespecíficos/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Resistencia a Antineoplásicos/genética , Humanos , Inmunoconjugados/uso terapéutico , Inmunoglobulina E/uso terapéutico , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Oncología Médica/tendencias , Neoplasias/genética , Neoplasias/inmunología , Neoplasias/mortalidad , Medicina de Precisión/tendencias , Supervivencia sin Progresión , Ingeniería de Proteínas , Radioinmunoterapia/tendencias , Escape del Tumor/genéticaRESUMEN
INTRODUCTION: The short range and high linear energy transfer of α-particles offer the potential for efficient tumor killing while sparing surrounding normal cells. Hematologic malignancies are ideally suited to targeted α-therapy because of easy accessibility of malignant cells in blood and bone marrow and their radiosensitivity. METHODS: A series of clinical trials were conducted to assess the safety and antileukemic effects of lintuzumab, an anti-CD33 antibody, labeled with the α-emitters bismuth-213 (213Bi) and actinium-225 (225Ac) in patients with acute myeloid leukemia (AML). RESULTS: Initial studies showed that 213Bi-lintuzumab had antileukemic activity and could produce remissions after partial cytoreduction with cytarabine. A phase I trial demonstrated that a single infusion of 225Ac-lintuzumab could be given safely at doses up to 111 kBq/kg with antileukemic activity at all dose levels studied. A second phase I study showed that 28% of older patients with untreated AML had objective responses after receiving fractionated-dose 225Ac-lintuzumab and low-dose cytarabine. A phase II study of 225Ac-lintuzumab monotherapy in this population produced remissions in 69% of patients receiving two fractions of 74 kBq/kg and 22% of patients receiving two 55.5-kBq/kg fractions. CONCLUSIONS: Studies with 213Bi-lintuzumab provided proof of principle for systemically administered α-particle therapy. 225Ac-lintuzumab was active against advanced AML and produced remissions in older patients with untreated AML in combination with low-dose cytarabine and as a single agent. These studies provide the rationale for development of 225Ac-lintuzumab in combination with a variety of agents in AML and in other hematologic malignancies such as myelodysplastic syndrome and multiple myeloma.
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Partículas alfa/uso terapéutico , Neoplasias Hematológicas/radioterapia , Radioinmunoterapia/métodos , Radioterapia/métodos , Actinio/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antimetabolitos Antineoplásicos/uso terapéutico , Bismuto/uso terapéutico , Ensayos Clínicos como Asunto/métodos , Terapia Combinada , Citarabina/uso terapéutico , Humanos , Radioinmunoterapia/tendencias , Radioterapia/tendenciasRESUMEN
There is a distinct need for new and second-line therapies to delay or prevent local tumor regrowth after current standard of care therapy. Intracavitary radioimmunotherapy, in combination with radiotherapy, is discussed in the present review as a therapeutic strategy of high potential. We performed a systematic literature search following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). The available body of literature on intracavitary radioimmunotherapy (iRIT) in glioblastoma and anaplastic astrocytomas is presented. Several past and current phase I and II clinical trials, using mostly an anti-tenascin monoclonal antibody labeled with I-131, have shown median overall survival of 19-25 months in glioblastoma, while adverse events remain low. Tenascin, followed by EGFR and variants, or smaller peptides have been used as targets, and most clinical studies were performed with I-131 or Y-90 as radionuclides while only recently Re-188, I-125, and Bi-213 were applied. The pharmacokinetics of iRIT, as well as the challenges encountered with this therapy, is comprehensively discussed. This promising approach deserves further exploration in future studies by incorporating several innovative modifications.
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Neoplasias Encefálicas/radioterapia , Glioma/radioterapia , Radioinmunoterapia/métodos , Anticuerpos Monoclonales/uso terapéutico , Neoplasias Encefálicas/patología , Glioma/patología , Humanos , Radioisótopos de Yodo/uso terapéutico , Radioinmunoterapia/tendencias , Radioisótopos de Itrio/uso terapéuticoAsunto(s)
Confidencialidad , Desarrollo de Medicamentos , Radioinmunoterapia , Animales , Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Citotoxinas/administración & dosificación , Desarrollo de Medicamentos/ética , Desarrollo de Medicamentos/historia , Desarrollo de Medicamentos/tendencias , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Radioinmunoterapia/historia , Radioinmunoterapia/métodos , Radioinmunoterapia/tendencias , Radioisótopos/administración & dosificaciónRESUMEN
Radioactive 125I seeds (RIS) interstitial implantation brachytherapy has been a first-line treatment for early-stage cancer of the prostate gland. However, its poor accuracy and homogeneity has limited its indication and hampered its popularization for a long time. Intriguingly, scholars based in China introduced computed tomography (CT)-guided technology to improve the accuracy and homogeneity of RIS implantation and broadened the indications. Then, they creatively designed and introduced three-dimensional printing coplanar template (3D-PCT) and 3D printing noncoplanar template (3D-PNCT) into the practice of RIS implantation. Use of such templates makes RIS implantation more precise and efficacious and aids preoperative planning, real-time dose optimization, and postoperative planning. However, studies on the standard workflow for 3D-PT-assisted CT-guided RIS implantation have not been published. Therefore, the China Northern Radioactive Seeds Brachytherapy Group organized multidisciplinary experts to formulate the guideline for this emerging treatment modality. This guideline aims at standardizing 3D-PT-assisted CT-guided RIS implantation procedures and criteria for selecting treatment candidates and assessing outcomes and for preventing and managing postoperative complications.
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Braquiterapia/tendencias , Neoplasias/radioterapia , Impresión Tridimensional/tendencias , Guías como Asunto , Humanos , Radioisótopos de Yodo/uso terapéutico , Radioinmunoterapia/métodos , Radioinmunoterapia/tendencias , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/tendenciasRESUMEN
The great progress of genetics research, during 2015-2017, will certainly influence all medical specialties including nuclear medicine. In nuclear medicine there are still problems to solve as to differentiate between infection, inflammation and cancer etc. Furthermore, in dosimetry and radiation protection there are worldwide problems. It has been reported that 64 Cu-cetuximab immune-PET represented EGFR expression levels in ESCC tumors and that 177 Lu-cetuximab radioimmunotherapy effectively inhibited the tumor growth. Recent important research findings and few related suggestions for further research are mentioned related to Gastroenterology, Neohippocratic Medicine, the Respiratory System, Neurology and the Hayflick phenomenon. Perhaps we now live in the genetics transformation era, the Genomie's Era.
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Investigación Genética , Neoplasias/genética , Neoplasias/radioterapia , Medicina Nuclear/tendencias , Medicina de Precisión/tendencias , Radioinmunoterapia/tendencias , Medicina Basada en la Evidencia , Juramento Hipocrático , HumanosRESUMEN
BACKGROUND: Patients with classical Hodgkin's lymphoma (cHL) have a good prognosis even in advanced stages. However, combined chemo- and radiotherapy, as the standard of care, is also associated with treatment-related toxicities such as organ damage, secondary neoplasias, infertility, or fatigue and long-term fatigue. Many patients suffer from this burden although their cHL was cured. Therefore, the efficacy of immune checkpoint inhibitors like anti-PD1/PD-L1 antibodies in the treatment of solid cancers and also in HL offers new options. A remarkable and durable response rate with a favorable toxicity profile was observed in heavily pretreated cHL patients. METHODS: Planning to perform prospective randomized clinical trials in the content of radio-immune treatment in patients with Hodgkin's lymphoma (HL), we transferred the results of preliminary clinical studies and basic research in clinical relevant study concepts. RESULTS: Based on these promising early phase trial data, the German Hodgkin Study Group (GHSG) will investigate innovative treatment regimens in upcoming phase II trials. CONCLUSION: The therapeutic efficacy and potential synergies of anti-PD1 antibodies in combination with chemo- or radiotherapy will be investigated in various settings of HL.
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Anticuerpos Monoclonales/uso terapéutico , Quimioradioterapia/tendencias , Enfermedad de Hodgkin/terapia , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Radioinmunoterapia/tendencias , Ensayos Clínicos Controlados Aleatorios como Asunto , Puntos de Control del Ciclo Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/inmunología , Quimioradioterapia/métodos , Predicción , Alemania , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/inmunología , Humanos , Terapia Molecular Dirigida/tendencias , Oncología por Radiación/tendencias , Radioinmunoterapia/métodos , Resultado del TratamientoRESUMEN
This review presents modern data about one of the promising direction in treatment of malignancies, which is called radioimmunotherapy. The special attention is paid to search of new targets and development of radiopharmaceuticals that will allow improving quality and accuracy of the directed impact on tumors of various localizations.
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Neoplasias/radioterapia , Radioinmunoterapia/métodos , Radiofármacos/uso terapéutico , Animales , Humanos , Neoplasias/inmunología , Neoplasias/patología , Radioinmunoterapia/tendenciasAsunto(s)
Neoplasias/radioterapia , Radioinmunoterapia/tendencias , Radioterapia de Intensidad Modulada/tendencias , Radioterapia/tendencias , Braquiterapia/tendencias , Terapia Combinada , Relación Dosis-Respuesta en la Radiación , Humanos , Neoplasias/patología , Protectores contra Radiación/uso terapéutico , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Radioisótopos/uso terapéuticoRESUMEN
Breast cancer is one of the most commonly diagnosed malignancies and is the main cause of death in women aged 40-49 years. Metastatic breast cancer is a heterogeneous disease that has a variety of different clinical presentations, ranging from solitary metastatic lesion to diffuse and multiple organ involvement. The biological heterogeneity of metastatic breast cancer has led to its unpredictable clinical behavior. One of the major challenges, therefore, is to identify predictive and prognostic models facilitating the selection of patients who can benefit from more aggressive and potentially curative options. This article provides an overview of the current management of metastatic breast cancer with focused emphasis on radioimmunotherapy.
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Anticuerpos Monoclonales/uso terapéutico , Neoplasias de la Mama/terapia , Terapia Combinada , Inmunotoxinas/uso terapéutico , Radioinmunoterapia/métodos , Animales , Antígenos de Neoplasias/inmunología , Neoplasias de la Mama/diagnóstico , Diagnóstico por Imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Radioinmunoterapia/tendencias , Tomografía Computarizada por Rayos XRESUMEN
Due to its ability to target both known and occult lesions, radioimmunotherapy (RIT) is an attractive therapeutic modality for solid tumors. Poor tumor uptake and undesirable pharmacokinetics, however, have precluded the administration of radioimmunoconjugates at therapeutically relevant doses thereby limiting the clinical utility of RIT. In solid tumors, efficacy of RIT is further compromised by heterogeneities in blood flow, tumor stroma, expression of target antigens and radioresistance. As a result significant efforts have been invested toward developing strategies to overcome these impediments. Further, there is an emerging interest in exploiting short-range, high energy α-particle emitting radionuclides for the eradication of minimal residual and micrometastatic disease. As a result several modalities for localized therapy and models of minimal disease have been developed for preclinical evaluation. This review provides a brief update on the recent efforts toward improving the efficacy of RIT for solid tumors, and development of RIT strategies for minimal disease associated with solid tumors. Further, some of promising approaches to improve tumor targeting, which showed promise in the past, but have now been ignored are also discussed.
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Neoplasias/inmunología , Neoplasias/terapia , Radioinmunoterapia/métodos , Radioinmunoterapia/tendencias , Partículas alfa , Animales , Anticuerpos Monoclonales/administración & dosificación , Modelos Animales de Enfermedad , Humanos , Inmunoconjugados/uso terapéutico , Neoplasia Residual , Peritoneo/efectos de la radiación , Radioisótopos/uso terapéutico , Radiofármacos/uso terapéuticoRESUMEN
When delivered at a sufficient dose and dose rate to a neoplastic mass, radiation can kill tumor cells. Because cancer frequently presents as a disseminated disease, it is imperative to deliver cytotoxic radiation not only to the primary tumor but also to distant metastases, while reducing exposure of healthy organs as much as possible. Monoclonal antibodies and their fragments, labeled with therapeutic radionuclides, have been used for many years in the development of anticancer strategies, with the aim of concentrating radioactivity at the tumor site and sparing normal tissues. This review surveys important milestones in the development and clinical implementation of radioimmunotherapy and critically examines new trends for the antibody-mediated targeted delivery of radionuclides to sites of cancer.
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Anticuerpos Monoclonales/uso terapéutico , Neoplasias/radioterapia , Radioinmunoterapia/métodos , Radioinmunoterapia/tendencias , Radioisótopos/uso terapéutico , Terapia Combinada , Humanos , Terapia Molecular Dirigida , Tolerancia a RadiaciónRESUMEN
Radioimmunotherapy is a well-known treatment for non-Hodgkin's lymphoma. (90)yttrium (Y)-ibritumomab-tiuxetan consists of a radioisotope conjugated to a monoclonal anti-cluster of differentiation 20 antibody, which is targeted against B-lymphocytes. Initially the treatment indication was relapse of low-grade non-Hodgkin's lymphoma. However, (90)Y-ibritumomab-tiuxetan has later been used in clinical trials in the treatment of other types of non-Hodgkin's lymphoma and prior to stem cell transplantation. Based on the literature this systematic review aims to throw light on the future possibilities of radioimmunotherapy.
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Linfoma no Hodgkin/radioterapia , Radioinmunoterapia , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Humanos , Linfoma Folicular/radioterapia , Linfoma de Células B Grandes Difuso/radioterapia , Linfoma de Células del Manto/radioterapia , Recurrencia Local de Neoplasia/radioterapia , Radioinmunoterapia/efectos adversos , Radioinmunoterapia/métodos , Radioinmunoterapia/tendencias , Trasplante de Células Madre , Resultado del TratamientoRESUMEN
Targeting of radionuclides with antibodies, or radioimmunotherapy, has been an active field of research spanning nearly 50 years, evolving with advancing technologies in molecular biology and chemistry, and with many important preclinical and clinical studies illustrating the benefits, but also the challenges, which all forms of targeted therapies face. There are currently two radiolabeled antibodies approved for the treatment of non-Hodgkin lymphoma, but radioimmunotherapy of solid tumors remains a challenge. Novel antibody constructs, focusing on treatment of localized and minimal disease, and pretargeting are all promising new approaches that are currently under investigation.
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Anticuerpos Biespecíficos/uso terapéutico , Sistemas de Liberación de Medicamentos , Neoplasias , Radioinmunoterapia , Radioisótopos/uso terapéutico , Animales , Anticuerpos Monoclonales/uso terapéutico , Sistemas de Liberación de Medicamentos/métodos , Sistemas de Liberación de Medicamentos/tendencias , Humanos , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/radioterapia , Neoplasias/inmunología , Neoplasias/radioterapia , Radioinmunoterapia/métodos , Radioinmunoterapia/tendenciasRESUMEN
Radioimmunotherapy relies on the principles of immunotherapy, but expands the cytotoxic effects of the antibody by complexing it with a radiation-emitting particle. If we consider radioimmunotherapy as a step beyond immunotherapy of cancer, the step was prompted by the (relative) failure of the latter. The conventional way to explain the failure is a lack of intrinsic killing effect and a lack of penetration into poorly vascularized tumor masses. The addition of a radioactive label (usually a ß-emitter) to the antibody would improve both. Radiation is lethal and the type of radiation used (beta rays) has a sufficient range to overcome the lack of antibody penetration. At present, the most successful (and FDA approved) radioimmunotherapy agents for lymphomas are anti-CD20 monoclonal antibodies. Rituximab (Rituxan(®)) is a chimeric antibody, used as a non-radioactive antibody and to pre-load the patient when Zevalin(®) is used. Zevalin(®) is the Yttrium-90 ((90)Y) or Indium-111 ((111)In) labeled form of Ibritumomab Tiuxetan. Bexxar(®) is the Iodine-131 ((131)I) labeled form of Tositumomab. Ibritumomab Tiuxetan and Tositumomab are murine anti-CD20 monoclonal antibodies, not chimeric antibodies. Promising research is being done to utilize radioimmunotherapy earlier in the treatment algorithm for lymphoma, including as initial, consolidation, and salvage therapies. However, despite more than 8 years since initial regulatory approval, radioimmunotherapy still has not achieved widespread use due to a combination of medical, scientific, logistic, and financial barriers. Other experimental uses for radioimmunotherapy include other solid tumors to treat infections. Optimization can potentially be done with pre-targeting and bi-specific antibodies. Alpha particle and Auger electron emitters show promise as future radioimmunotherapy agents but are mostly still in pre-clinical stages.