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Clinical Outcomes

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Glioma

Continuum Cancer Centers of New York (CCCNY) has been active in developing intensive treatment programs for patients with central nervous system (CNS) tumors that coordinate the use of surgery, radiation, and chemotherapy. This multidisciplinary team approach has significantly improved the control of cancer in these patients.

According to the American Cancer Society, each year approximately 23,000 people in the United States are diagnosed with a brain tumor. Unfortunately, in 2013, more than 14,000 patients with this diagnosis will die from their cancer.

Gliomas are the most common type of primary (non-metastatic) brain tumor. They develop from glial cells, which support brain cells. There are several types of gliomas, based on the subtype of cell from which they arise and how aggressive the tumor appears histologically (under the microscope), ranging from low-grade glioma to the very aggressive glioblastoma. Glioblastoma is the most common brain cancer in adults. The tumors arise from the star-shaped astrocyte cells, which support the brain’s nerve cells. Because glioblastomas tend to spread through the brain tissue, they can be difficult to remove completely.

High-grade gliomas (HGG) are classified Grade III or Grade IV by the World Health Organization (WHO). These high-grade lesions have anaplastic (very abnormal) histology and the ability to infiltrate.

WHO Grade III tumors have histological evidence of malignancy that includes nuclear atypia (an odd-looking cell nucleus) and increased cell division (mitotic) activity, signaling rapid growth. They are usually treated with intensive post surgery (adjuvant) therapy. Anaplastic astrocytoma, a common Grade III glioma, grows quickly and spreads into nearby tissues.

WHO Grade IV gliomas include lesions that are mitotically active, cause cell death (necrosis), grow rapidly before and after surgery, and are usually fatal. A glioblastoma, sometimes called glioblastoma multiforme, is a Grade IV cancer arising from an astrocyte. It grows and spreads very quickly, with a low chance of cure despite maximal surgery, radiation therapy, and chemotherapy.

Radiation therapy has a major role in the adjuvant treatment of HGG’s after the most complete safe resection. Multiple randomized trials and meta-analyses have shown that patients who receive adjuvant radiation therapy live longer than those patients who do not. Usually, the standard accepted dose of radiation therapy is delivered over six weeks (30 treatments). Moreover, the standard practice has been to incorporate chemotherapy (temozolamide, or Temodar) along with radiation therapy and for several months thereafter. This approach has led to longer patient survival as reported in the New England Journal of Medicine in 2005 (Stupp R, Mason WP, van den Bent MJ, et al.: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352 (10): 987-96, 2005).

In summary, this standard of care practice, which incorporates maximal surgery followed by chemoradiation and adjuvant chemotherapy, leads to approximately 26.5% of patients surviving at 2 years and 10.9% at 5 years (Stupp R, Hegi ME, Mason WP, et al.: Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomized phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10 (5): 459-66, 2009).

We recently looked at the long-term outcomes of patients treated at our institution by this approach between 2005 through 2012. Ninety-six patients (48 male and 48 female) with Grade III and IV gliomas were treated with definitive radiation therapy at CCCNY. Their median age was 60 years (range: 18-89 years). After a median radiation dose of 60 Gy administered with chemotherapy, approximately 30% of patients were alive at 2 years and 20% at 5 years. (See Figure 1.) Only seven of the total patients had Grade III cancers, and the remaining 89 patients had Grade IV cancers, or glioblastoma. Approximately 29% of patients with glioblastoma were alive at 2 years after diagnosis and 17% at 5 years. (See Figures 2 & 3.) All of the patients received surgery, radiation therapy, and chemotherapy.

Based on long-term observation, combined chemoradiation is needed to achieve comparable (or slightly better) overall survival outcomes as in the published literature. However, the slightly better survival rates at CCCNY compared to the national standard may be due to differences in the patients we saw, the molecular biology of their tumors, or perhaps novel treatment techniques we used, such as IMRT (intensity-modulated radiation therapy) or IGRT (image-guided radiation therapy).

While giving radiation therapy and chemotherapy remains the mainstay of adjuvant treatment for HGG/glioblastoma after maximally safe surgery, the cure rates for this disease remain poor. In order to build on the achievements here at CCCNY, our multidisciplinary CNS cancer team has developed a set of clinical trials that may improve these patients’ outcomes. For more information about research studies, click here

Overall Survival – All HGGs (including Grade III & IV)
Figure 1. Overall Survival – All HGGs (including Grade III & IV)

Overall Survival stratified by Grade
Figure 2. Overall Survival stratified by Grade

Overall Survival for Patients with Glioblastoma
Figure 3. Overall Survival for Patients with Glioblastoma


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