have reviewed the MRI, and indeed there is a tumor obscuring the pons within the brainstem, with engulfment of the basilar artery, and extending to the midbrain (mesencephalon) and partly to the medulla. The tumor is hypo- to iso-intense on T1- weighted images, and hyperintense on T2. There is minimal enhancement with gadolinium dye. There is mild hydrocephalus.
Following initiation of dexamethasone (Decadron, steroid for vasogenic edema), the child has been treated at the National Cancer Institute of Milan and has started experimental treatment with the medicine nimotuzumab to be followed with conventional radiotherapy. This is a very logical and reasonable approach for this very aggressive, and often refractory malignant brain tumor/cancer.
(1) What therapy do you suggest? If you exclude the surgical operation, do you share the pharmacologic therapy + diagnosed radiotherapy? Is there the possibility after the diagnosed therapy, that the tumoral mass could decrease, allowing later a solving surgical operation?
I would strongly suggest the therapeutic approach that has been adopted. In North America, Europe, and South America, the leading, upfront clinical trials for this dreadful tumor have been:
- nimotuzumab + radiotherapy (a phase II study being performed at selected children’s hospital in Europe, Canada, and the United States)
- arsenic trioxide + radiotherapy (a I study being performed at selected children’s hospital in the United States)
- ACNS 0222 gadolinium texaphyrin + radiotherapy (a phase II study conducted by the Children’s Oncology Group at children’s hospitals throughout the United States and Canada; just recently closed)
- PBTC -021 capecitabine and radiotherapy (a phase I Trial being conducted at 8 centers in the United States)
At Stanford, we have been participating in all of the 3 first named studies (nimotuzumab, arsenic trioxide, and gadolinium texaphyrin). While there are no data to indicate any of these experimental treatments are more effective than radiotherapy alone, we would favor either nimotuzumab or arsenic trioxide plus radiotherapy
Any meaningful surgical resection of this tumor is not possible without devastating, catastrophic neurologic injury, or a bad outcome. Tumors such these diffusely infiltrate all the normal tissue of the brainstem, such that the cancer cannot be removed without destroying the normal tissue of the brainstem.
A limited biopsy could be performed but would not change the treatment plans or outcome in any way.
If the tumor were to grow further after nimotuzumab, we would proceed with bevacizumab plus or minus temozolomide or irinotecan, either on or off an experimental, clinical trial.
(2) Do his parents know that the radiotherapy is applicable only once in the same point; afterwards does it exist a follow-up therapy for this kind of tumor that can give long-term and good quality life expectancies?
Conventional external beam radiotherapy (photon or less often proton) can be done only once in a lifetime with this tumor. Without any radiation, the average life expectancy is about only 20 weeks. With radiation, the average life expectancy is 1 year, though we would be hopeful that the patient exceeds well that average.
After radiotherapy, we would consider continuing the nimotuzumab or initiating bevacizumab or temozolomide.
(3) Now the young patient is taking cortisone that involves an excessive increasing in his appetite compared to his real needs. Is it advisable to regulate the amount and/or to opt for particular types and quality of food? Is it necessary to contact a nutritionist?
We would strongly advise trying to minimize the usage of dexamethasone (or cortisone) to the lowest amount tolerable, so as to minimize these many side-effects. Most often we can get children down to a dose of 1 to 2 mg dexamethasone twice a day (along with the Nexium to avoid stomach upset). At the same time, we would make sure that the child is not allowed to eat excessively: he can take regular meals, but then if he is still hungry after meals, he should be offered lowest calorie foods such as carrots or celery without any spreads or dressings. A nutritionist may be helpful for advice.
4) What will the pathology course be? Will the symptomatology be very painful?
These diffuse tumors are all grade II-IV diffuse, non-operable astrocytomas (malignant brain cancers). [Fisher PG et al. A clinicopathologic reappraisal of brainstem tumor classification: identification of pilocytic astrocytoma and fibrillary astrocytoma as distinct entities. Cancer 89:1569-1576, 2000]. As the tumor progresses, rarely ever is pain a problem. Instead, children have progressive difficulty with crossed eyes, weak face, difficulty swallowing, and walking. If the tumor is refractory and not responsive to any treatment, the child often lapses into a deep sleep/coma for days or weeks before passing peacefully.
(5) What are the centres of excellence for the treatment of such pathologies in Italy and Europe?
- Giorgio Perilongo at University of Padua is an expert Italian neuro-oncologist, well trained in the United States.
- Jacques Grill is another expert neuro-oncologist in France at Département de Cancérologie de l'Enfant et de l'Adolescent, Institut Gustave Roussy, 39, rue Camille Desmoulins, Villejuif cedex 94805, France.
- Great Ormond Street Hospital for Children in London is another center of excellence.