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Combining radiation plus immunotherapy to improve systemic immune response.

ABSTRACT: Over the past decade, the fields of oncology have made great strides in therapies. The development of new therapeutics and increased understanding of the role of the immune system in the development and treatment of cancer has led to increased collaboration between oncologic fields. Recent technologic advancements in radiation therapy (RT), including stereotactic beam radiation therapy (SBRT), have improved local control and offer an alternative to surgery for the control of oligometastatic disease. Immunotherapy has proven a promising therapeutic in the treatment of metastatic disease but treatment resistance remains a significant obstacle in the majority of patients. Together, radiation and immunotherapy offer potential to eliminate metastatic disease, reduce time to recurrence and improve overall survival. Major obstacles to these positive outcomes include high tumor burden, intratumoral heterogeneity, and the negative effects of tumor stroma, to name a few. Multimodality treatments are under heavy investigation. Promising data from clinical trials is emerging to highlight the value of RT in combination with immunotherapy. However, the mechanisms behind their synergistic effects remain to be fully elucidated. This review aims to highlight the existing literature and offers hypotheses to explain mechanisms behind the synergy of RT and immunotherapy.

SUBMITTER: Cushman TR

PROVIDER: S-EPMC5861265 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Combining radiation plus immunotherapy to improve systemic immune response.

Cushman Taylor R TR Gomez Daniel D Kumar Rachit R Likacheva Anna A Chang Joe Y JY Cadena Alex P AP Paris Sebastien S Welsh James W JW

Journal of thoracic disease 20180201 Suppl 3

Over the past decade, the fields of oncology have made great strides in therapies. The development of new therapeutics and increased understanding of the role of the immune system in the development and treatment of cancer has led to increased collaboration between oncologic fields. Recent technologic advancements in radiation therapy (RT), including stereotactic beam radiation therapy (SBRT), have improved local control and offer an alternative to surgery for the control of oligometastatic dise ...[more]

PMID: 29593892

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Project description:Local radiation therapy (RT) combined with systemic anti-cytotoxic T-lymphocyte-associated protein-4 immunotherapy may enhance induction of systemic antimelanoma immune responses. The primary objective of the present trial was to assess the safety and efficacy of combining ipilimumab with RT in patients with stage IV melanoma. The secondary objectives included laboratory assessment of induction of antimelanoma immune responses.In our prospective clinical trial, 22 patients with stage IV melanoma were treated with palliative RT and ipilimumab for 4 cycles. RT to 1 to 2 disease sites was initiated within 5 days after starting ipilimumab. Patients had ?1 nonirradiated metastasis measuring ?1.5 cm available for response assessment. Tumor imaging studies were obtained at baseline, 2 to 4 weeks after cycle 4 of ipilimumab, and every 3 months until progression. Laboratory immune response parameters were measured before and during treatment.Combination therapy was well-tolerated without unexpected toxicities. Eleven patients (50.0%) experienced clinical benefit from therapy, including complete and partial responses and stable disease at median follow-up of 55 weeks. Three patients (27.3%) achieved an ongoing systemic complete response at a median follow-up of 55 weeks (range 32-65), and 3 (27.3%) had an initial partial response for a median of 40 weeks. Analysis of immune response data suggested a relationship between elevated CD8-activated T-cells and response.This is the second prospective clinical trial of treatment of metastatic melanoma using the combination of RT and systemic immunotherapy and the first using this sequence of therapy. The results from the present trial demonstrate that a subset of patients may benefit from combination therapy, arguing for continued clinical investigation of the use of RT combined with immunotherapy, including programmed cell death 1 inhibitors, which might have the potential to be even more effective in combination with RT.

Dataset Information

Combining radiation plus immunotherapy to improve systemic immune response.

Publications

Combining radiation plus immunotherapy to improve systemic immune response.

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