The lancet oncology
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Evidence to date shows that immune checkpoint inhibitors have little benefit in most patients with head and neck squamous cell carcinoma (HNSCC). Intense interest is focused on identifying and developing rational combinations of immune checkpoint inhibitors and different therapeutic interventions to enhance response rates and overcome immune checkpoint inhibitor resistance. Combining radiotherapy, a primary HNSCC treatment modality, with immunotherapy has been shown to induce potent antitumour immune responses in many cancers including HNSCC. ⋯ In this Series paper, we examine how radiotherapy can be used to its maximum therapeutic potential in the setting of immunotherapy treatment for HNSCC by focusing on published clinical and preclinical data. We rely on preclinical evidence for this disease to discuss how radiotherapy can help create and maintain an immunologically permissive environment. Our hope is that such mechanistic insights will provide a foundation for maximising the use of radioimmunotherapy in disease control, designing future trials, interpreting emerging immunotherapy data, and accelerating discovery within radioimmunotherapy interventions for HNSCC.
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The lancet oncology · Aug 2019
ReviewIntegration of radiotherapy and immunotherapy for treatment of oligometastases.
Metastasis is the leading cause of cancer-related mortality and remains one of the prevailing challenges in cancer treatment. Most patients with metastatic disease are treated with systemic agents, which prolong survival and improve symptoms but are typically not curative. ⋯ Improvements in clinical and molecular staging of metastatic disease, as well as integration of effective systemic therapies with localised interventions, might achieve better outcomes for patients with diverse metastatic states. In this Series paper, we propose a rationale for the integration of immune checkpoint inhibitors with radiotherapy to advance the potential for effective treatment along the spectrum of disease, with emphasis on how immunotherapy can potentiate radiotherapy treatment in the oligometastatic setting.
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The lancet oncology · Aug 2019
ReviewRational combinations of immunotherapy with radiotherapy in ovarian cancer.
Except for its use in palliative care, radiotherapy has been largely abandoned in the management of ovarian cancer because of the recognised efficacy and lower toxicity of systemic chemotherapy compared with radiotherapy. New data have emerged that show synergy of radiotherapy with immunotherapy to control or eradicate cancer. ⋯ This Series paper discusses the past and present use of radiotherapy for ovarian cancer, and the mechanisms by which radiotherapy can mobilise anticancer immunity. We provide emerging preclinical and clinical data for combining immunotherapy with radiotherapy for ovarian cancer treatment and offer a clinical development roadmap to guide the next generation of clinical trials for this combination strategy for this disease.
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The lancet oncology · Aug 2019
ReviewEnhancing CAR T-cell therapy through cellular imaging and radiotherapy.
Chimeric antigen receptor (CAR) T-cell therapy is one of the most remarkable advances in cancer therapy in the last several decades. More than 300 adoptive T-cell therapy trials are ongoing, which is a testament to the early success and hope engendered by this line of investigation. ⋯ In this Series paper, we discuss the short-term strategies to improve CAR T-cell therapy responses, particularly for solid tumours, by combining CAR T-cell therapy with radiotherapy through the use of careful monitoring and non-invasive imaging. Through the use of imaging, we can gain greater mechanistic insights into the cascade of events that must unfold to enable tumour eradication by CAR T-cell therapy.
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The lancet oncology · Aug 2019
ReviewOptimising efficacy and reducing toxicity of anticancer radioimmunotherapy.
Immunotherapy is radically changing the clinical management of patients affected by an increasingly wide array of tumours. However, not all patients achieve long-term clinical benefits from immunotherapy as a standalone treatment, calling for the development of regimens that combine various interventions. ⋯ However, optimal radioimmunotherapy regimens might call for the redefinition of conventional radiotherapy doses and fractionation schedules. In this Series paper, we discuss current approaches to improve the efficacy and reduce the toxicity of radioimmunotherapy for the management of cancer.