Eric C. Ko

Radiation therapy remains a cornerstone in the clinical care of patients with medulloblastoma. Nevertheless, while treatment with radiation improves disease control, it is also associated with potential late effects impacting neurologic and neurocognitive function, pituitary function as well as hearing. The development of secondary, treatment-related malignancies is an uncommon but possible late outcome. In this chapter, we review the role of radiation therapy in medulloblastoma, as well as changes in management that have resulted both from technological therapeutic advancements and enterprising cooperative group clinical trials for this disease. Moreover, with increasing utilization of molecular diagnostics both for prognosis and stratification of treatment, we also endeavor to explore opportunities to further improve the delivery of radiation therapy to patients with varied risk of disease recurrence.

Medulloblastoma is the most common malignant brain tumor in children. Prognosis remains guarded in patients who at diagnosis are very young, have craniospinal metastatic disease, or after resection, have residual disease. Treatment incorporates chemotherapy and radiation therapy. Cancer survivors often have life-altering treatment effects. This chapter reviews clinical trials over the years and the efforts to improve survival and minimize sequelae along with challenges in performing clinical trials. Quality assurance of the radiation therapy provided worldwide monitors compliance. Advances in the risk stratification and targeted treatment based on the genomics and biology of medulloblastoma are highlighted in recent clinical trials. Through chemotherapy aligned with specific biomarkers, sophisticated radiation therapy strategies, and continued quality assurance, the future vision of managing medulloblastoma is presented.

Tweetable abstract Immunotherapy for head and neck cancer shows promising new directions – and challenges ahead. What can we learn from recent trials to improve patient selection and optimize combi...

Editorial Stereotactic body radiation therapy for metastatic non-small cell lung cancer: a versatile treatment, repurposed James L. Shen, Eric C. Ko

Purpose of Review Positive results from recent immunotherapy trials of non-small cell lung cancer (NSCLC) have coincided with a greater appreciation for the impact of radiation therapy (RT) on tumor immunity. Here, we summarize key clinical findings and ongoing efforts to combine immunotherapy and RT for the treatment of NSCLC. Recent Findings The role of immunotherapy for NSCLC has expanded significantly following the pivotal approvals of nivolumab and pembrolizumab for metastatic NSCLC, maintenance durvalumab in unresectable stage III NSCLC, and atezolizumab for metastatic NSCLC. Several small early-phase trials have demonstrated the ability of RT to elicit clinically significant tumor immunity. These positive findings support current trial efforts combining RT with immunotherapy for NSCLC. Summary Recently initiated trials of RT and immunotherapy hold significant promise in expanding the therapeutic options for NSCLC. Optimization of therapy will require careful patient selection to yield meaningful improvements in clinical outcomes.

Purpose: The aim of this review is to highlight key evidence supporting the effect of radiation therapy on tumor immunity. Conclusions: Recent findings in both the preclinical and clinical settings have provided convincing evidence of the ability of radiation therapy to influence tumor-directed immune responses, and have offered critical insights into the underlying mechanisms. Not only does radiation therapy convert the tumor microenvironment to promote robust tumor immunity, but it also enhances the generation of neoantigens and neoepitopes. Radiation therapy also shapes the TCR repertoire of CD8⁺ T cells in conjunction with immune checkpoint blockade. In conclusion, a high priority should be placed on developing rational strategies to integrate radiation therapy with immunotherapy in the clinical setting, with an emphasis on careful patient selection and identifying important correlative endpoints.

Five-year survival rates for non–small cell lung cancer (NSCLC) range from 14% to 49% for stage I to stage IIIA disease, and are <5% for stage IIIB/IV disease. Improvements have been made in the outcomes of patients with NSCLC due to advancements in radiotherapy (RT) techniques, the use of concurrent chemotherapy with RT, and the emergence of immunotherapy as first- and second-line treatment in the metastatic setting. RT remains the mainstay treatment in patients with inoperable early-stage NSCLC and is given concurrently or sequentially with chemotherapy in patients with locally advanced unresectable disease. There is emerging evidence that RT not only provides local tumor control but also may influence systemic control. Multiple preclinical studies have demonstrated that RT induces immunomodulatory effects in the local tumor microenvironment, supporting a synergistic combination approach with immunotherapy to improve systemic control. Immunotherapy options that could be combined with RT include programmed cell death-1/programmed cell death ligand-1 blockers, as well as investigational agents such as OX-40 agonists, toll-like receptor agonists, indoleamine 2,3-dioxygenase-1 inhibitors, and cytokines. Here, we describe the rationale for the integration of RT and immunotherapy in patients with NSCLC, present safety and efficacy data that support this combination strategy, review planned and ongoing studies, and highlight unanswered questions and future research needs.

Immune checkpoint blockade has recently emerged as an important therapeutic approach to the management of malignancies across multiple disease settings. Concomitantly, there has been an increasing appreciation for the role of radiotherapy in eliciting and promoting tumor-directed immune responses. In this review, we discuss the clinical evidence to date on combinations of radiotherapy with immune checkpoint inhibitors, both from the standpoint of safety and efficacy. We highlight important but yet-unanswered questions for this combination approach, as well as their implications for future prospective studies.