Radiotherapy for craniopharyngioma

Radiotherapy remains the mainstay of multidisciplinary management of patients with incompletely resected and recurrent craniopharyngioma. Advances in imaging and radiotherapy technology offer new alternatives with the principal aim of improving the accuracy of treatment and reducing the volume of normal brain receiving significant radiation doses. We review the available technologies, their technical advantages and disadvantages and the published clinical results. Fractionated high precision conformal radiotherapy with image guidance remains the gold standard; the results of single fraction treatment are disappointing and hypofractionation should be used with caution as long term results are not available. There is insufficient data on the use of protons to assess the comparative efficacy and toxicity. The precision of treatment delivery needs to be coupled with experienced infrastructure and more intensive quality assurance to ensure best treatment outcome and this should be carried out within multidisciplinary teams experienced in the management of craniopharyngioma. The advantages of the combined skills and expertise of the team members may outweigh the largely undefined clinical gain from novel radiotherapy technologies.     

Teaching Medical Students About Cancer Impact Through a Longitudinal Surgical Experience: A Case Study

Background: We designed and execute a longitudinal curriculum that provides a comprehensive understanding of cancer illness and its impact upon the patient. Summary: The Harvard Medical School–Cambridge Integrated Clerkship is a redesign of the 3rd year where the traditional rotations are replaced by a single integrated year-long experience. Students are required to follow a patient with newly diagnosed gastrointestinal cancer and breast cancer, across all venues and disciplines. Twenty-nine of 34 students responded to a survey. On average patients were followed for 7 months, through 12 encounters across 4 different specialties. Students responded that this experience facilitated their understanding of cancer in a way not feasible in a traditional clerkship model. Conclusions: Medical students perceive that this longitudinal model of cancer education improves integration of the surgical, medical, scientific, emotional, and social issues. Traditional “block rotation” students and even residents are rarely afforded such an educational opportunity.     

Fenretinide enhances rituximab-induced cytotoxicity against B-cell lymphoma xenografts through a caspase-dependent mechanism

The anti-CD20 monoclonal antibody rituximab induces remission in 40% to 60% of patients with indolent B-cell lymphoma, but virtually all patients have relapses. We evaluated the efficacy of concurrent administration of another biologic agent, N-(4-hydroxyphenyl) retinamide (4HPR, fenretinide) with rituximab against a variety of human B-cell lymphoma cell lines (Ramos, DHL-4, and FL-18) in vivo. Concurrent 4HPR and rituximab administration prevented tumor progression of lymphoma-bearing mice in a minimal disease model (rituximab + 4HPR, 100% progression free; rituximab alone, 37.5% progression free, P =.01; 4HPR alone, 12.5% progression free, P <.01; controls, 0% progression free, P <.01). Combinations of 4HPR + rituximab exceeded the predicted 50% additive rate of disease control from each agent alone (P =.038). Administering 4HPR and rituximab to mice with established tumors induced complete responses (CRs) in 80% of animals compared with 20% to 40% CRs using either agent alone (P =.07), resulting in significantly improved survival. Tumors harvested from 4HPR + rituximab-treated mice displayed elevated caspase activation compared with untreated controls (P =.02). Adding a broad-spectrum caspase inhibitor in vivo fully abrogated the antitumor effects of 4HPR + rituximab (P =.05). These results establish the efficacy of 4HPR/rituximab combinations, confirm their caspase-mediated mechanism of action, and offer the potential for disease control with minimal toxicity for patients with B-cell malignancies.     

Aicardi syndrome: epilepsy surgery as a palliative treatment option for selected patients and pathological findings

The optimal treatment for medically refractory epilepsy in Aicardi syndrome (AS) is still unclear. Palliative surgical treatment, including vagus nerve stimulation and corpus callosotomy, has therefore been used. There is limited data on the role of resective epilepsy surgery as a treatment choice in patients with AS. Here, we describe the seizures, anatomo‐pathological findings, and neurodevelopmental outcome of palliative epilepsy surgery in two children with AS who had resective epilepsy surgery at the Cleveland Clinic. The related literature is also reviewed. Case 1 had a left functional hemispherectomy and was free of seizures and hypsarrhythmia for six months after surgery. Her gross motor skills improved after surgery. Outcome at 43 months was 1–3 isolated spasms per day. Case 2 had a right fronto‐parietal lobectomy. Her seizures improved in frequency and severity, but remained daily after epilepsy surgery. Neurodevelopment changes included improved alertness and recognition of caregivers. This patient died 21 months after epilepsy surgery of unclear causes. Surgical pathology in both cases showed focal cortical dysplasia associated with other findings, such as nodular heterotopia and polymicrogyria. Epilepsy surgery could be an alternative palliative treatment choice in selective cases of AS, but studies on a larger patient cohort are needed to identify the possible role of surgery in children with AS. The complexity of the pathological findings may offer an explanation for the severity of seizures in AS.