Christopher S. Platta

Current Treatment Strategies for Brain Metastasis and Complications From Therapeutic Techniques A Review of Current Literature

Each year approximately 170,000 patients are diagnosed with brain metastasis in the United States, making this the most common intracranial tumor in adults. Historically, treatment strategies focused on the use of whole brain radiation therapy (WBRT) for palliation, yielding a median survival time of only 3 to 6 months. The possible effect of WBRT on cognitive function has generated much concern and debate regarding the use of this modality. Thus, the use of WBRT alone, or in conjunction with other treatment modalities should take into account both risks and benefits, to ensure the best patient outcome with regard to disease state and functional status. The advent of technologies permitting local dose-escalation have clearly increased local control rates, and in select patients, even survival, thereby, further intensifying the debate regarding the use of WBRT. Here, we review the use of WBRT, radiosurgery, and resection for the treatment of brain metastases. Further, we will review the use of radiation sensitizers and blood–brain barrier penetrating cytotoxics such as temozolomide. Finally, we will discuss current treatment strategies for possibly maintaining and improving cognitive function for these patients.

Valproic Acid Induces Notch1 Signaling in Small Cell Lung Cancer Cells

BACKGROUND Small cell lung cancer (SCLC) is an aggressive malignancy. Current treatments yield dismal survival rates. We have previously demonstrated that histone deacetylase (HDAC) inhibitors can inhibit neuroendocrine tumor growth. Activation of the Notch1 signaling pathway also impairs SCLC cell viability. In this study, we investigated the ability of the HDAC inhibitor valproic acid (VPA) to activate Notch1 signaling and inhibit proliferation in SCLC cells. MATERIALS AND METHODS DMS53 human SCLC cells were treated with VPA (0-10 mM) for 2 d. Light microscopy was used to examine changes in cell morphology. Western analysis was performed using antibodies against various Notch1 pathway proteins to assess Notch1 activation. Additionally, immunoblotting was performed for two neuroendocrine tumor markers, chromogranin A and achaete-scute complex-like 1. Finally, a cell proliferation assay was used to measure the effects of VPA on SCLC growth over 8 d. RESULTS After treatment with VPA, DMS53 cells underwent dramatic changes in morphology. VPA induced expression of the full-length and active forms of Notch1 protein. Furthermore, VPA suppressed levels of neuroendocrine tumor markers chromogranin A and ASLC-1. Importantly, VPA treatment led to dose-dependent inhibition of SCLC cell proliferation. CONCLUSIONS The HDAC inhibitor VPA activates Notch1 signaling in SCLC cells. VPA induces changes in cell morphology and suppresses neuroendocrine tumor markers, indicating a change in phenotype. Additionally, VPA profoundly inhibits SCLC cell growth. These results suggest that VPA has potential as a novel therapeutic agent for SCLC.

Pituitary Adenoma: A Radiotherapeutic Perspective

Pituitary adenomas comprise approximately 10% to 20% of all central nervous system neoplasms whereas autopsy series have suggested that the incidence of pituitary adenoma in the general population may approach 25%. Several treatment modalities are used in the treatment of pituitary adenomas, including observation, surgery, medical intervention, and radiotherapy. The treatment modality employed depends greatly on the type of pituitary adenoma and presenting symptoms. This review will discuss the biology of pituitary adenomas and the current management principles for the treatment of prolactinomas, Cushing disease, acromegaly, and nonsecretory adenomas, with an emphasis on the published radiotherapeutic literature.

Adjuvant and definitive radiation therapy for primary carcinoma of the vagina using brachytherapy and external beam radiation therapy

Purpose To report the outcomes of patients receiving vaginal brachytherapy and/or external beam radiation therapy (EBRT) for primary vaginal cancer. Material and methods Between 1983 and 2009, 63 patients received brachytherapy and/or EBRT for primary tumors of the vagina at a single tertiary center. Patient data was collected via chart review. The Kaplan-Meier method was used to calculate actuarial pelvic local control (LC), disease-free survival (DFS), overall survival (OS), and severe late toxicity rates. Acute and late toxicities were scored according to the Common Terminology Criteria for Adverse Events version 3 (CTCAE v3.0). Results Median follow up was 44.2 months. Patients with early stage disease (stages I and II) had significantly improved 5-year OS when compared to patients with locally advanced disease (stages III and IVA) (73.3 vs. 34.4%, p = 0.032). Patients with greater than 1/3 vaginal involvement had significantly worse prognosis than patients with tumors involving 1/3 or less of the vagina, with the later having superior DFS (84.0 vs. 52.4%, p = 0.007) and LC (86.9 vs. 60.4%, p = 0.018) at 5-years. Age, histology, and brachytherapy technique did not impact treatment outcomes. The 5-year actuarial grade 3 or higher toxicity rate was 23.1% (95% CI: 10.6-35.6%). Concurrent chemotherapy had no impact on outcomes or toxicity in this analysis. Conclusions Success of treatment for vaginal cancer depends primarily on disease stage, but other contributing factors such as extent of vaginal involvement and tumor location significantly impact outcomes. Treatment of vaginal cancer with primary radiotherapy yields acceptable results with reasonable toxicity rates. Management of this rare malignancy requires a multidisciplinary approach to appropriately optimize therapy.

Low Rates of Heterotopic Ossification After Resurfacing Hip Arthroplasty With Use of Prophylactic Radiotherapy in Select Patients

Recent reports have noted higher rates of heterotopic ossification (HO) with surface replacement arthroplasty (SRA) than with traditional total hip arthroplasty in the absence of postoperative HO prophylaxis. This study reports rates and grades of HO in 44 SRA patients with at least 1 year of follow-up. Heterotopic ossification prophylaxis was used in 32 (73%) of 44 cases. Heterotopic ossification prophylaxis consisted of radiotherapy (22/32), nonsteroidal anti-inflammatory drugs (8/32), or both (2/32). One case of clinically significant HO was documented in the no-prophylaxis group. This strategy of selective HO prophylaxis in patients felt by orthopedic surgeons to be at high risk of HO resulted in low rates of clinically relevant HO after SRA (1/44, 2.3%). Further study is needed to establish optimal selection criteria for HO prophylaxis after SRA.

Cervical brachytherapy technique for locally advanced carcinoma of the cervix in a patient with septate uterus

Purpose To describe an approach to cervical brachytherapy in a patient with congenital septate uterus and locally advanced cervical carcinoma. Material and methods The patient is a 34-year-old female with septate uterus presenting with pelvic pain. Workup demonstrated a stage IIB cervical adenocarcinoma with imaging evidence of an involved right external iliac lymph node. The patient received whole pelvic radiation, with concurrent weekly cisplatin (40 mg/m2), to a dose of 45 Gy in 25 fractions followed by a parametrial boost of 5.4 Gy and an additional nodal boost of 9 Gy. Results The patient was initiated on cervical brachytherapy following fraction 23 of pelvic radiation. To conform to her septated uterus, a Rotte-Y tandem was used. Additionally, 2 CT-compatible ovoids were placed in the vaginal apex to enhance dose distribution and coverage of the target volume. Each fraction of brachytherapy was performed with CT-based planning. A high-risk clinical target volume (HR-CTV) and normal structures were defined and constrained per American Brachytherapy Society (ABS) and Groupe Européen de Curiethérapie/European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) guidelines. The brachytherapy dose was 27.5 Gy in 5 fractions of 5.5 Gy each, prescribed to the HR-CTV. Conclusions Herein, we report the first documented case of cervical brachytherapy in a patient with septate uterus and locally advanced cervical carcinoma. Using CT-guided planning, in conjunction with the ABS and GEC-ESTRO guidelines, the patient was effectively treated with adapted cervical brachytherapy, meeting criteria for HR-CTV coverage and normal tissue tolerances.