Irradiation and immunotherapy: From concept to the clinic

Salama, April K.S.; Postow, Michael A.; Salama, Joseph K.

doi:10.1002/cncr.29889

Cited by 77 publications

(56 citation statements)

References 88 publications

(116 reference statements)

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“…While FLC is generally characterized by a low mutational load in comparison to other cancers, next-generation sequencing of tumor tissue revealed the presence of MSH2 mutations with a frequency of 41% as a marker of genomic instability in our patient. Furthermore, there is evidence that radiation therapy induces a synergistic anti-tumor response in combination with checkpoint inhibitors through multiple effects on cancer cells and on the tumor microenvironment [21]. Stereotactic irradiation of cerebral metastasis and the presence of a marker for genomic instability therefore seemed be predictors of a favorable response to immunotherapy in our patient.…”

Section: Discussionmentioning

confidence: 94%

Progression after Immunotherapy for Fibrolamellar Carcinoma

et al. 2019

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Background: Fibrolamellar carcinoma (FLC) is a rare malignancy of the liver that differs from typical hepatocellular carcinoma (HCC) in several aspects such as the absence of underlying liver disease and occurrence in younger patients. Even though the survival rates in FLC are slightly better than in typical HCC, the prognosis of metastatic FLC remains deleterious. Several reports suggest that systemic chemotherapy regimens can successfully be used to halt disease progression in FLC, while targeted tumor therapy with sorafenib seems to be of limited efficiency. However, results from controlled clinical trials investigating systemic therapies in FLC are virtually nonexistent. Therefore, the choice of treatment often relies on case series with limited numbers of patients. Immunotherapy with checkpoint inhibitors is an emerging cancer therapy in several solid malignancies including HCC. Currently, there do not exist any reports on the use of checkpoint inhibitors in FLC. Case Report: Here, we describe a case of advanced FLC in a young man receiving immunotherapy, who progressed after 3 months of treatment – similar to 2 other patients with advanced FLC at our hospital. Conclusion: While immunotherapy seems to be a promising treatment with limited side effects in several other tumor entities, there is currently no data supporting tumor response in FLC.

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Section: Discussionmentioning

confidence: 94%

Progression after Immunotherapy for Fibrolamellar Carcinoma

et al. 2019

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“…As a basic cytokine stimulating the immune system, GM-CSF plays its therapeutic role against cancer by potentiating the antitumor effects of other molecules or treatments, such as RT [5, 18]. The interactions between this cytokine and treatment are complex, with impact on prognosis and survival being rarely investigated.…”

Section: Discussionmentioning

confidence: 99%

Elevated serum granulocyte-macrophage colony-stimulating factor levels during radiotherapy predict favorable outcomes in lung and esophageal cancer

Deng

Zhang

et al. 2016

Oncotarget

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The combination of exogenous granulocyte-macrophage colony-stimulating factor (GM-CSF) with radiotherapy (RT) has been demonstrated to strengthen the antitumor immune response. We hypothesized that the variation of GM-CSF during RT was correlated with cancer prognosis. We measured serum levels of GM-CSF and interferon-γ (IFN-γ) before and during RT in 126 unresectable lung and esophageal cancer patients and performed survival analyses. Upregulated GM-CSF levels during RT correlated with longer overall survival (OS) and progression-free survival (PFS). On the other hand, no difference in OS or PFS was seen at different IFN-γ levels. However, the “integrated factor”, computed as the combination of high pre-RT IFN-γ levels and upregulated GM-CSF, correlated with prolonged OS and PFS. Multivariate analyses revealed that GM-CSF levels and the integrated factor were both stronger independent prognostic factors than disease stage. These data demonstrate that GM-CSF levels during RT can be used as a prognostic biomarker for lung and esophageal cancer.

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“…Furthermore, radiation therapy or chemotherapy may also prove to be effective partners for talimogene laherparepvec or talimogene laherparepvec combination regimens [60–62]. In addition to direct tumor cell cytotoxicity, localized radiation therapy and chemotherapeutic agents can also lead to systemic responses through immunomodulatory effects both on the tumor and the microenvironment [61, 63, 64]. This process can prime tumors for an immune-mediated response and may enhance efficacy as part of a combination strategy.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Combining talimogene laherparepvec with immunotherapies in melanoma and other solid tumors

Dummer

Höeller

Gruter

et al. 2017

Cancer Immunol Immunother

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Talimogene laherparepvec is a first-in-class intralesional oncolytic immunotherapy. In a recent Phase III trial (OPTiM), talimogene laherparepvec significantly improved durable response rate compared with subcutaneous granulocyte–macrophage colony-stimulating factor (GM-CSF). Overall response rate was also higher in the talimogene laherparepvec arm, and the greatest efficacy was demonstrated in patients with earlier-stage (IIIB, IIIC, or IVM1a) melanoma. Talimogene laherparepvec was well tolerated, with the majority (89%) of adverse events being grade 1 or 2. Preclinical studies have shown that talimogene laherparepvec exerts antitumor activity by selectively replicating within and destroying cancer cells, and through the release of tumor-associated antigens and expression of GM-CSF, which facilitates a wider antitumor immune response. It is hypothesized that combining talimogene laherparepvec with a systemic immunotherapy may, by bringing together complementary mechanisms of action, further enhance the efficacy of both agents. Indeed, talimogene laherparepvec is currently being assessed in combination with immune checkpoint inhibitors, including ipilimumab and pembrolizumab, in trials for melanoma and other solid tumors. Early results in melanoma indicate that the combination of talimogene laherparepvec with ipilimumab or pembrolizumab has greater efficacy than either therapy alone, without additional safety concerns above those expected for each monotherapy. In this review, we discuss the latest results from trials assessing talimogene laherparepvec in combination with other immunotherapies, provide an overview of ongoing and upcoming combination trials, and suggest future directions for talimogene laherparepvec in combination therapy for solid tumors.

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Irradiation and immunotherapy: From concept to the clinic

Cited by 77 publications

References 88 publications

Progression after Immunotherapy for Fibrolamellar Carcinoma

Progression after Immunotherapy for Fibrolamellar Carcinoma

Elevated serum granulocyte-macrophage colony-stimulating factor levels during radiotherapy predict favorable outcomes in lung and esophageal cancer

Combining talimogene laherparepvec with immunotherapies in melanoma and other solid tumors

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