Nicole Shonka

Central Nervous System Cancers, Version 2.2014: Featured Updates to the NCCN Guidelines

For many years, the diagnosis and classification of gliomas have been based on histology. Although studies including large populations of patients demonstrated the prognostic value of histologic phenotype, variability in outcomes within histologic groups limited the utility of this system. Nonetheless, histology was the only proven and widely accessible tool available at the time, thus it was used for clinical trial entry criteria, and therefore determined the recommended treatment options. Research to identify molecular changes that underlie glioma progression has led to the discovery of molecular features that have greater diagnostic and prognostic value than histology. Analyses of these molecular markers across populations from randomized clinical trials have shown that some of these markers are also predictive of response to specific types of treatment, which has prompted significant changes to the recommended treatment options for grade III (anaplastic) gliomas.

Atypical Teratoid/Rhabdoid Tumors in Adults: A Case Report and Treatment-Focused Review

Atypical teratoid/rhabdoid tumor is predominantly a childhood tumor and has only been rarely reported in adults; therefore, treatment regimens are often extrapolated from the pediatric experience. Typically, children are treated with craniospinal radiation therapy which is often followed by systemic chemotherapy. Employing pediatric regimens to treat this tumor in adult patients poses a particular risk for myelosuppression, as the prescribed doses in pediatric protocols exceed those tolerated by adults, and conventional craniospinal radiation can be associated with prolonged myelotoxicity and a depletion of the bone marrow reserve in vertebrae of adults. Here we present a case of a woman with a pineal region atypical teratoid/rhabdoid tumor, an unusual adult cancer presenting in an atypical location. This is followed by a review of the disease in adult patients with an emphasis on treatment and suggestions to minimize myelotoxicity. Keywords Atypical rhabdoid tumor; AT/RT; Pineal tumor; Adult

Effect of diabetes mellitus on the epidemiology and outcomes of colon cancer

ObjectivesTo assess the effect of diabetes mellitus (DM) on the pathogenesis and outcomes from colon cancer.MethodsA retrospective chart review was conducted on 1853 patients with colon cancer.ResultsA higher percentage of males than females with colon cancer had DM (16.2% vs 11.3%; p<0.01). Males had a slightly lower risk of dying from colon cancer (RR−0.88; p=0.08). There was no difference in the median age of diagnosis of colon cancer in patients with and without DM, but a larger proportion of patients with diabetes mellitus were ≥70 yr at diagnosis (50% vs 43%) (p=0.0004). No significant relationship was noted between stage of colon cancer or survival and presence of DM.ConclusionsDM did not affect either the stage at diagnosis, or outcomes from colon cancer. More males with colon cancer tended to have DM and a larger proportion of patients with DM were ≥70 yr at the time of diagnosis.

Pancytopenia due to iron deficiency worsened by iron infusion: a case report

IntroductionIron deficiency anemia is commonly associated with thrombocytosis, although thrombocytopenia has been reported in occasional patients with iron-deficiency anemia. Much less common is the development of thrombocytopenia following replenishment of iron stores.Case PresentationWe present the unusual case of a 39 year old African American female Jehovahs Witness who presented with a 10 month history of menorrhagia and pancytopenia. Laboratory investigations confirmed a severe iron deficiency. Since blood transfusion was unacceptable to her, she was started on intravenous iron replacement therapy. This precipitated a sudden drop in both her platelet and white blood cell counts. Histopathological examination of the bone marrow revealed a hypercellular marrow with orderly trilineage hematopoiesis, iron deficiency anemia, granulocytic hyperplasia, and mild megakaryocytic hypoplasia. Both her white blood cell and platelet counts recovered uneventfully with continuing iron supplementation. The possible mechanism for this phenomenon is discussed in this report.ConclusionThis case illustrates two rather uncommon associations of a very common problem. Severe iron deficiency anemia may be associated with pancytopenia and iron replacement may cause a transient decline in megakaryopoiesis and leukopoiesis. Severe iron deficiency should be added to the list of conditions leading to thrombocytopenia.

Targets for therapy in ependymoma

Ependymomas are among the rarest type of glioma and display significant heterogeneity based on patient age and tumor location. Treatment strategies include surgery and radiation, but the use of chemotherapy remains more controversial. Chemotherapy has been widely utilized in the pediatric population due to more aggressive disease in this cohort, and has become of interest in the adult population as well. Unfortunately, relapses are common, and responses to cytotoxic chemotherapy are often disappointing. As a result, attention has turned to specific targets in the pathogenesis of ependymoma. This paper summarizes the current understanding of promising molecular pathways and targets under study for future application in ependymoma.

Targeted Treatment of Brain Metastases

Purpose of ReviewBrain metastases are the most common intracranial tumors in adults. Historically, the median survival after the diagnosis of brain metastases has been dismal and medical therapies had a limited role in the management of these patients.Recent FindingsThe advent of targeted therapy has ushered in an era of increased hope for patients with brain metastases. The most common malignancies that result in brain metastases—melanoma, lung cancer, and breast cancer, often have actionable mutations, which make them good candidates for targeted systemic therapy. These brain metastases have been shown to have relevant and sometimes divergent genetic alterations, and there has been a resurgence of interest in targeted drug delivery to the brain by using standard or pulsatile dosing to achieve adequate concentration in the brain.SummaryAn increased understanding of oncogenic alterations, a surge in targeted drug development with good blood barrier penetration, and inclusion of patients with active brain metastases on clinical trials have led to improved outcomes for patients with brain metastases.

EGFR monoclonal antibodies in locally advanced head and neck squamous cell carcinoma: What is their current role?

Treatment options for locally advanced squamous cell carcinoma of the head and neck (SCCHN) include either surgical resection followed by radiation or chemoradiation, or definitive chemoradiation for which single-agent cisplatin is the best studied and established. The increasing understanding of the molecular biology of SCCHN has led to an interest in the development of targeted therapies. The epidermal growth factor receptor (EGFR) is over-expressed in nearly 80-90% of cases of SCCHN and correlates with poor prognosis and resistance to radiation. Preclinical evidence showed that blocking EGFR restores radiation sensitivity and enhances cytotoxicity. This finding led to clinical trials evaluating this class of agents and the approval of cetuximab in combination with radiation for the treatment of locally advanced SCCHN. This review is focused on the anti-EGFR monoclonal antibodies and their role either with radiotherapy or chemoradiation in unresectable LA SCCHN.

Intrathecal interleukin-2 for melanomatous meningitis.

Introduction One person dies as a result of melanoma every 64 minutes in the United States; it is the most common cancer killer in women age 30 to 35 years. Melanoma is among the three cancers most likely to spread to the leptomeninges, with a 23% rate of meningeal spread. In a retrospective review of 110 patients with melanomatous meningitis (MM), median overall survival from time of diagnosis of MM was 10 weeks. The majority of patients with MM and leptomeningeal disease from other solid tumors are frequently treated with intrathecal methotrexate, cytarabine, thiotepa, or topotecan, but published reports of treatment with intrathecal interleukin (IT IL-2) are rare. This report describes a patient with MM who was treated with IT IL-2 and experienced subsequent extended survival. Case Report A 23-year-old white woman was diagnosed with stage IIB melanoma of the upper extremity after wide resection and sentinel lymph node biopsy. Ten months later, metastatic disease developed, requiring palliative resection of a large chest wall mass and axillary lymph node dissection. A positron emission tomography scan demonstrated bilateral pulmonary nodules and bilateral hilar adenopathy. Magnetic resonance imaging (MRI) of the brain showed multiple enhancing lesions. Palliative whole-brain radiation was given, followed by two courses of high-dose IL-2 systemic therapy. A restaging positron emission tomography scan demonstrated an excellent partial response of the lung disease. Five months later, lower extremity neurologic deficits developed. MRI of the thoracic and lumbar spine showed multiple intramedullary masses and significant spinal cord edema from the fourth through eleventh thoracic vertebral levels (T4 through T11). Radiation therapy (RT; 30 Gy) was administered to T3 to T12 over 2 weeks. Immediately after finishing RT, temozolomide (200 mg/m per day for 5 days) was begun; however, during the last day of RT and the first few days of

Undifferentiated Embryonal Sarcoma of Liver.

Undifferentiated embryonal sarcoma of the liver (UESL) is a rare malignant hepatic tumor. A 47 year old male presented with symptoms of sour taste in his mouth, occasional nausea, indigestion and 15-pound weight loss over two months. He had an unremarkable upper gastrointestinal endoscopy. Imaging showed a large liver mass in the left hepatic lobe that was resected and then reported as UESL. He went on to develop lung metastases and was initially treated with doxorubicin and ifosfamide followed by switching of therapy to gemcitabine and docetaxel due to progression of disease. He had a good response after two cycles and went on to receive four more cycles, achieving stable disease. We can therefore conclude that the combination of gemcitabine and docetaxel is a potential therapeutic option for patients with UESL.

Near Misdiagnosis of Glioblastoma as Primary Central Nervous System Lymphoma

Primary central nervous system (CNS) lymphoma, most frequently a diffuse large B-cell lymphoma, is a rare aggressive lymphoma confined to the CNS, thus requiring differentiation from other brain malignancies such as glioblastoma. Although stereotactic biopsy can confirm the diagnosis, this is invasive, not always feasible and can be inconclusive after steroid use. Hence, cranial magnetic resonance imaging (MRI) with contrast and cerebrospinal fluid analysis are frequently used to make a prompt diagnosis. We report a case of a woman with two brain masses who presented unique diagnostic challenge.