Therapeutic cancer vaccines for pediatric malignancies: advances, challenges, and emerging technologies.

Though outcomes for pediatric cancer patients have significantly improved over the past several decades, too many children still experience poor outcomes and survivors suffer lifelong, debilitating late effects after conventional chemotherapy, radiation, and surgical treatment. Consequently, there has been a renewed focus on developing novel targeted therapies to improve survival outcomes. Cancer vaccines are a promising type of immunotherapy that leverage the immune system to mediate targeted, tumor-specific killing through recognition of tumor antigens, thereby minimizing off-target toxicity. As such, cancer vaccines are orthogonal to conventional cancer treatments and can therefore be used alone or in combination with other therapeutic modalities to maximize efficacy. To date, cancer vaccination has remained largely understudied in the pediatric population. In this review, we discuss the different types of tumor antigens and vaccine technologies (dendritic cells, peptides, nucleic acids, and viral vectors) evaluated in clinical trials, with a focus on those used in children. We conclude with perspectives on how advances in combination therapies, tumor antigen (eg, neoantigen) selection, and vaccine platform optimization can be translated into clinical practice to improve outcomes for children with cancer.

An updated assessment of morbidity and mortality following skull base surgical approaches.

OBJECTIVES: Updated multi-institutional database studies assessing perioperative risk factors on 30-day morbidity and mortality after skull base surgeries are limited. We aim to identify perioperative risk factors and report the incidence of 30-day morbidity and mortality in adult patients after skull base surgery. PATIENTS AND METHODS: We queried the 2007-2016 American College of Surgeons National Surgical Quality Improvement program database to identify patients who underwent anterior, middle, or posterior skull base surgery. We performed multivariable logistic regression to identify risk factors associated with 30-day morbidity and mortality. Postoperative events were compared between propensity score matched cohorts (no morbidity versus 30-day morbidity). RESULTS: The final analysis included 1028 adult (≥18 years old) patients. The incidence of 30-morbidity and mortality was 14.6% and 1.6%, respectively. Postoperative ventilator dependence (52.9%) followed by pneumonia (23.5%) and unplanned intubation (23.5%) had the highest prevalence among those with 30-day mortality. The adjusted odds of 30-day morbidity was significantly higher among patients with functional dependency, American Society of Anesthesiologists Physical Status ≥4, hyponatremia, and anemia (p < 0.05). The adjusted odds of 30-day mortality was significantly increased among patients with sepsis, bleeding disorder, disseminated cancer, and older age (p < 0.05). CONCLUSION: Clinical perioperative factors are significantly associated with 30-day morbidity and mortality after skull base surgery. The reported rate of 30-day morbidity and mortality was similar to earlier studies and therefore highlights the need for continued quality improvement.