Abscopal Effect on Hepatocellular Carcinoma

Nakanishi, M.; Chuma, Makoto; Hige, Shuhei

doi:10.1111/j.1572-0241.2007.01782_13.x

Cited by 49 publications

(34 citation statements)

References 8 publications

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“…TNF-α is capable of inducing cell death and activate natural killer cells and thus applied in several experimental regimens as a cancer treatment [42]. In contrast, Nakanishi et al performed the same cytokine panel, also in a patient with HCC, but without a notable increase in TNF-α [43]. They did note a rise in IL-18 both before and after radiotherapy.…”

Section: Discussionmentioning

confidence: 99%

The abscopal effect of local radiotherapy: using immunotherapy to make a rare event clinically relevant

Reynders

Illidge

Siva

et al. 2015

Cancer Treatment Reviews

498

405

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Background Recently, immunologic responses to localized irradiation are proposed as mediator of systemic effects after localized radiotherapy (called the abscopal effect). Here, we give an overview of both preclinical and clinical data about the abscopal effect in particular and link them with the immunogenic properties of radiotherapy. Methods We searched Medline and Embase with the search term “abscopal” from 1960 until July, 2014. Only papers that cover radiotherapy in an oncological setting were selected and only if no concurrent cytotoxic treatment was given. Targeted immune therapy was allowed. Results Twenty-three case reports, one retrospective study and 13 preclinical papers were selected. Eleven preclinical papers used a combination of immune modification and radiotherapy to achieve abscopal effects. Patient age range (28 to 83 years) and radiation dose (median total dose 32 Gy) varied. Fractionation size ranged from 1,2 Gy to 26 Gy. Time to documented abscopal response ranged between less than one and 24 months, with a median reported time of 5 months. Once an abscopal response was achieved, a median time of 13 months went by before disease progression occurred or the reported follow-up ended (range 3–39 months). Conclusion Preclinical data points heavily towards a strong synergy between radiotherapy and immune treatments. Recent case reports already illustrate that such a systemic effect of radiotherapy is possible when enhanced by targeted immune treatments. However, several issues concerning dosage, timing, patient selection and toxicity need to be resolved before the abscopal effect can become clinically relevant.

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Section: Discussionmentioning

confidence: 99%

The abscopal effect of local radiotherapy: using immunotherapy to make a rare event clinically relevant

Reynders

Illidge

Siva

et al. 2015

Cancer Treatment Reviews

498

405

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“…Thus, therapeutic (as opposed to unwarranted) abscopal reactions have been documented in patients bearing a wide variety of neoplasms, including (but presumably not limited to) lymphoma, 146 - 150 melanoma, 151 - 154 primary and metastatic breast carcinoma, 155 - 158 adenocarcinoma, 159 , 160 sarcoma 161 hepatocellular carcinoma, 162 , 163 Merkel cell carcinoma, 164 renal cell carcinoma (RCC), 165 and uterine cancer 166 …”

Section: Immunogenic Effects Of Radiotherapymentioning

confidence: 99%

“…Initially, clinicians tended to consider the abscopal effect as a straightforward systemic consequence of the local release of immunostimulatory and cytotoxic cytokines, mainly TNFα 163 and IL-18, 162 by irradiated (malignant and immune) cells. However, it is now clear that—at least under specific circumstances—radiation therapy elicits an adaptive immune response against malignant cells that is capable of mediating robust antineoplastic effects on non-irradiated lesions 167 - 170 .…”

Section: Immunogenic Effects Of Radiotherapymentioning

confidence: 99%

Trial Watch

Vacchelli

Vitale²,

Tartour

et al. 2013

OncoImmunology

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Radiotherapy has extensively been employed as a curative or palliative intervention against cancer throughout the last century, with a varying degree of success. For a long time, the antineoplastic activity of X- and γ-rays was entirely ascribed to their capacity of damaging macromolecules, in particular DNA, and hence triggering the (apoptotic) demise of malignant cells. However, accumulating evidence indicates that (at least part of) the clinical potential of radiotherapy stems from cancer cell-extrinsic mechanisms, including the normalization of tumor vasculature as well as short- and long-range bystander effects. Local bystander effects involve either the direct transmission of lethal signals between cells connected by gap junctions or the production of diffusible cytotoxic mediators, including reactive oxygen species, nitric oxide and cytokines. Conversely, long-range bystander effects, also known as out-of-field or abscopal effects, presumably reflect the elicitation of tumor-specific adaptive immune responses. Ionizing rays have indeed been shown to promote the immunogenic demise of malignant cells, a process that relies on the spatiotemporally defined emanation of specific damage-associated molecular patterns (DAMPs). Thus, irradiation reportedly improves the clinical efficacy of other treatment modalities such as surgery (both in neo-adjuvant and adjuvant settings) or chemotherapy. Moreover, at least under some circumstances, radiotherapy may potentiate anticancer immune responses as elicited by various immunotherapeutic agents, including (but presumably not limited to) immunomodulatory monoclonal antibodies, cancer-specific vaccines, dendritic cell-based interventions and Toll-like receptor agonists. Here, we review the rationale of using radiotherapy, alone or combined with immunomodulatory agents, as a means to elicit or boost anticancer immune responses, and present recent clinical trials investigating the therapeutic potential of this approach in cancer patients.

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“…Mole described systemic effects of radiotherapy observed at non-irradiated sites in animals after localized radiotherapy [1]. Multiple case studies have described the abscopal effect, with a variety of malignancies including lymphoma, papillary adenocarcinoma, and melanoma, adenocarcinoma of the oesophagus, chronic lymphocytic leukaemia and hepatocellular carcinoma (HCC) [2][3][4][5][6][7][8][9][10][11][12][13]. Takaya et al described an abscopal effect in toruliform para-aortic lymph node metastasis in a patient with advanced uterine cervical carcinoma.…”

Section: Introductionmentioning

confidence: 99%

Proposed approach for revealing unknown mediators of the abscopal effect

Seidi

Zarghami

Jahanban‐Esfahlan

2013

Journal of Medical Hypotheses and Ideas

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It is sometimes asserted, as a matter of dogma, that a local treatment cannot have systemic effects. However, treatment with radiotherapy directly localized on a tumour can profoundly affect tumour cells in the other tissues far from the radiated part. In 1953, Dr. Mole called this surprising phenomenon the 'abscopal effect'. Since its discovery, very little is known about the exact mechanism and the key mediators of this astonishing phenomenon and many other questions in this context still remain unanswered. An understanding of this phenomenon could help to control the fatal face of cancer which is metastasis, and this discovery in turn will introduce promising strategies for treatment of advanced and not-curable cancers. Based on current information, we propose that there is a particular molecule(s) or macromolecule(s) that mediate(s) the abscopal effect. We also speculate that the frequency of the abscopal effect varies between different tumour types and the newly discovered molecule(s) or macromolecule(s) can enhance/instigate the abscopal effect in those tumour types that show a low frequency of the abscopal effect.

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Abscopal Effect on Hepatocellular Carcinoma

Cited by 49 publications

References 8 publications

The abscopal effect of local radiotherapy: using immunotherapy to make a rare event clinically relevant

The abscopal effect of local radiotherapy: using immunotherapy to make a rare event clinically relevant

Trial Watch

Proposed approach for revealing unknown mediators of the abscopal effect

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