Appeal type: Experimental/Investigational
Decision: Overturned Decision of Health Plan

Physician 1:  The patient is an 18-year-old young man first noted to have some numbness in his right arm in November 2005. It progressively worsened over the next few months, and by April 2006 he had right arm numbness and weakness along with neck pain. An MRI of the spine revealed a 3.9 x 1.2 x 1.4 cm enhancing lesion at C2 to C4. The lesion was partially excised in early May 2006. The final histopathologic diagnosis is glioblastoma (GBM).  The June 2006 spine MRI shows no change in the size of the enhancing lesion (suggesting that less was removed than thought or that the tumor has grown back to its original size). The patient improved after the operation, but according to his mother, his neurologic symptoms (tingling and weakness) are returning. The patients providers have recommended Avastin and CPT-11 as initial therapy. The Health Plan has denied this request on the basis that the therapy at issue is experimental in this clinical setting.The Health Plan points out that the standard of care for patients with GBM is radiation plus low-dose temozolomide. However, with this standard of care the outcomes for patients with GBM are quite poor. Furthermore, this standard of care has been established in patients who, for the most part, have supratentorial glioblastoma because that is by far the most common location for this tumor. Spinal cord GBM is exceedingly rare, and as a result, there is no established standard of care for patients with disease in this location. It appears that the outcome for these patients is just as poor, if not worse, than patients with supratentorial glioblastoma.The location of a brain tumor seems to have an impact on patient outcome. One reason a glioblastoma in the cervical spine might result in a worse outcome relates to the risk of post-radiation edema and inflammation. This phenomenon is common and while it can be tolerated in the supratentoria compartment, even a mild increase in edema could have devastating consequences in the cervical spine.Since the patient has a rare and potentially lethal disease, the standard of care is the judgment of an experienced multidisciplinary group at a center where many patients are seen and decision-makers can draw on extensive clinical experience. Such is the case for this patient. The judgment of this group is to try Avastin and CPT-11. The rationale is that this treatment has proven extraordinarily effective for patients with recurrent malignant glioma, and if it can substantially reduce the size of the cervical tumors, radiation can be more safely delivered. Experience with this therapy is growing. There are three Phase II studies in which the response rate in patients with recurrent malignant glioma is greater than 50%, an unprecedented response rate for patients in this setting.In sum, the patient has a rare, potentially lethal disease. There is no proven standard of care for spinal cord GBM. The proposed treatment has a reasonable chance to reduce the size of the mass, enable the team to deliver radiation more safely and thereby allow the patient to life a longer and better life. Therefore, I have determined that the therapy at issue is likely to be more beneficial for treatment of the patients medical condition than any available standard therapy. The Health Plans denial should be overturned.Physician 2:  The patient is an 18-year-old male with newly diagnosed glioblastoma multiforme (GBM) of the spinal cord. The patient underwent partial surgical excision. His providers have recommended a regimen of Avastin and CPT-11. The Health Plan has denied coverage for the therapy indicating there is insufficient evidence of its efficacy for treatment of the patients disease.Historically, patients with GBM do very poorly particularly when the tumor is on the spinal cord. Very little data exists regarding specific treatment of GBM in the spinal cord, as this is a rare condition. However, in extrapolating results from GBM treatment in general, the data shows that use of Temodar would be likely to result in statistical improvement in survival in patients with GBM of the spine.CPT-11 has been used in high-risk malignant glioma patients, including GBM. Papers by Reardon, et. al. and Turner, et. al. show that adult and pediatric data exist demonstrating clinical activity with CPT-11. Avastin has been used less extensively in this setting. However, there is one study showing 7 of 14 patients treated had MRI reductions after as little as two weeks of therapy (although CPT-11 was also included).Given the poor outcomes known to occur with radiation, and the lack of proven benefit of radiation and Temodar, it is likely the proposed regimen will be more effective for this patient than standard of care treatment. Accordingly, the Health Plans denial should be overturned.Physician 3:  The patient is an 18-year-old male with high-grade glioma incompletely resected from the spine. It was recommended the patient receive Avastin and CPT-11 and the patient has begun the therapy. The Health Plan has denied coverage for the recommended regimen on the basis that it is considered experimental.Given the rarity of the patients tumor, adequate clinical trials cannot be performed. Treatment should be considered on a case-by-case basis and by analogy to more common gliomas. Data are encouraging for the proposed regimen, which is likely to be of greater benefit in previously untreated disease settings than in the setting of tumor refractory to TMZ or BCNU, the standard alkylators used in this disease (along with radiation therapy, which is felt not to be feasible for this patient). Therefore, I have determined that the therapy at issue is likely to be more beneficial for treatment of the patients medical condition than any available standard therapy. The Health Plans denial should be overturned.