Treatment options for grade III ogliodendroglioma
Dear OncoLink "Ask The Experts,"
My 36 year-old brother was recently been diagnosed with a grade III ogliodendroglioma in his right temporal lobe. The tumor was large, 8.3 mm, and he had surgery to remove it. The neurosurgeon got 95% of the tumor out and put in Giadel wafers as well. We are considering treatment options and are confused. We have been told that radiation therapy and chemotherapy late effects outweigh the risks of waiting to see if there is tumor recurrence. I feel my brother should do radiation and chemo while he's young and healthier. What could be side effects from radiation to that area and how severely could they affect day-to-day function? Would Gamma Knife and chemo be the better choice for what remains? I'm worried that if we do not attack the cancer leftover now, the tumor will most certainly return and the treatments will have to be applied anyway. Why not do it now while my brother is physically and mentally ready to fight? Your help would be appreciated!
Hui-Kuo G. Shu, MD, PhD, Assistant Professor in the Department of Radiation Oncology at the University of Pennsylvania, responds:
The standard therapy for all malignant gliomas is to attain as good a resection as possible followed by radiation therapy +/- chemotherapy. Gliomas, by nature, are infiltrative tumors and despite maximal surgery, some residual (whether visible or not on post-operative imaging) is invariably left behind. Radiation therapy is therefore used to treat this residual disease to hopefully prevent or delay potential recurrences. Gliomas can show either astrocytic, oligodendroglial or mixed differentiation. Multiple studies have shown that oligodendrogliomas tend to have better prognosis than astrocytomas and this fact may be a consideration in what adjuvant therapy to offer. The question of what sort of adjuvant therapy to offer for a WHO grade III, or anaplastic oligodendroglioma is one that is now more complex with the identification of markers that may predict response to chemotherapy and overall outcome. Recent reports show that many anaplastic oligodendrogliomas have a specific deletion of a portion of chromosome 1 and 19. These chromosomal deletions are highly correlated with responsiveness to chemotherapy and outcome. Therefore, knowing the chromosomal status of the tumor may provide valuable prognostic information. Given our understanding of this tumor, it is typically recommended radiation therapy and, most likely, chemotherapy for a patient in this circumstance regardless of the chromosomal status. However, if the deletion(s) is (are) present, this would portend an extremely good prognosis and response to therapies. Conversely, if the deletions are not present, this tumor would be less likely to respond to chemotherapy and this would definitely portend a worse prognosis. While some reports in the literature actually advocate using chemotherapy alone (after surgery) in patients with this chromosome 1 deletion and a normal p53 status, this approach (with omission of radiation therapy) still requires further validation in clinical trials.
Conformal radiation therapy to the partial brain is generally relatively well tolerated. Acutely, patients experience some level of fatigue and may start to experience headaches especially as the treatment proceeds. There will also be focal hair loss depending on the entrance and exit of the radiation portals as well as varying levels of skin reaction. Radiation reaction in the brain can occur leading to some increased edema and swelling in the area of treatment with side effects dependent on location in the brain (for example, reaction in the dominant temporal lobe may actually lead to some speech deficits because of effects in the speech center). Overall, these acute side effects are generally not excessive and the patient receiving radiation therapy could still expect to be able to do most of the things that they could do prior to the start of radiation. Late effects may include some neurocognitive impairments including decreases in memory. However, recent data from a group at the Children's Hospital of Philadelphia studying the effect of conformal radiation therapy on neurocognitive outcomes in adults seems to suggest that radiation therapy to the partial brain causes much less neurocognitive sequelae than was previously thought.
As far as what type of radiation therapy to use, I would recommend 3-D conformal therapy and would not advocate using radiosurgery (either delivered via a linear accelerator or a gamma knife unit). There are biologic advantages to giving an extended fractionated course of radiation therapy (typically given over 30 to 33 treatments) over a single, high dose treatment as is typical for radiosurgery. Radiosurgery as a boost to standard conformal therapy has been studied clinically but to date has not proven to be significantly better than a regular extended course of conformal radiation therapy.
In summary, the general recommendations for any patient in this situation would be 3-D conformal therapy to tumor plus margin with chemotherapy (the standard is probably PCV - Procarbazine, CCNU and Vincristine). These radiation treatments are generally extremely well tolerated and is likely to produce relatively minimal side effects that have been enumerated above.