Anaplastic Astrocytoma in the left temporal lobe
Short Summary

65-year-old male experienced loss of consciousness, and a CT scan showed a left temporal mass which was confirmed by MRI. The patient underwent Stereotacti biopsy of mass, and Histological examination gave a diagnosis of anaplastic astrocytoma. He started chemoradiation with fotemustine (nitrosourea alkylating agent). Repeated MRI showed progression with mass effect, mild uncal herniation and enlarging ventricles. He has stable expressive aphasia and hemisyndrome, lethargy and decreased motivation. His treatment was switched from phenobarbital to levetiracetam.


Patient's Questions
1)         Do you confirm the treatment in place?

2)         Is it possible to consider surgical intervention?

3)         Which are the Centers of Excellence in Italy?

4)         Prognosis?
Medical Background

Patient's History
Diagnosis: Anaplastic Astrocytoma in the left temporal lobe
Sex : M
No significant conditions in past medical history with the exception of the recent onset of steroid diabetes.
On Jan 2008, the patient arrived at the Emergency Room of the San Raffaele Hospital in Milan following two episodes of loss of consciousness. In addition, the patient reported episodes of mental confusion and disorientation for several months. He then underwent a CAT scan of the brain which showed the presence of a left temporal expansive lesion.
The patient was therefore hospitalized in the Neurosurgery Clinic of the same hospital for tests and necessary care; upon admittance to the ward, neurological evaluation was within normal limits.
During his stay, the patient underwent:
-           NMR of the brain: confirmed and better delineated the previously detected left temporal lesion with frontoinsular extension, with maximum diameter of 4 cm.
-           Chest X-ray: no acute pleural and parenchymal lesions.
-           On Jan, the patient underwent stereotactic surgery under sedation and local anesthesia to perform a biopsy of the detected lesion.
Post-operative course was normal; follow-up CAT scan of the brain showed normal post-surgery results. The patient developed steroid diabetes during his stay which required the administration of insulin to achieve good glycemic control. Histological examination gave a diagnosis of anaplastic astrocytoma.
On Feb 2008, the patient was evaluated by the radiation therapist who prescribed radiation therapy treatment.
On Feb 2008, the patient was evaluated by the oncologist who prescribed chemotherapy.
The patient was discharged on Feb with the following treatment plan prescribed:
-           Esopral (Esomeprazole Magnesium, Nexium) 1 tablet per day;
-           Gardenale (Phenobarbital, Gardenal) 100 mg 1 tablet at 8 PM;
-           Gardenale (Phenobarbital, Gardenal) 50 mg 1 tablet at 8 AM;
-           Tenormin (Atenonol) 100 mg 1 tablet at 12 Noon;
-           Soldesam (Dexamethasone) 64 drops 2 times per day (8 AM – 8 PM) for 5 days;
-           Humalog 4 units at 8 AM – 6 units at 12 Noon – 6 units at 6 PM.
Radiation therapy concomitant with Muphoran (fotemustine) was performed as prescribed.
The NMR of the brain from May 2008 revealed a neuroradiologic picture of disease progression, in particular:
“..expansion of the multiple independent cystic necrotic portions previously reported with some evidence of their current fusion/coalescence. Some lesion portions recognizable at the last check as areas of nodular enhancement on the level of the left basal ganglia region are now remarkably larger in size, and particularly the lesion located at the genu of the internal capsule. A coin lesion located at the level of the posterolateral portion of the left superior orbital gyrus is significantly larger in size, as well. In addition, the appearance of new small nodular components is detected at the left hippocampal gyrus. The multifocal lesion is surrounded by peripheral edematous reaction and affects flattening of the corresponding cortical sulci and the Sylvian fissure, as well as impressing the left lateral ventricle. The left occipital horn is moderately enlarged: this fact, which is worth checking, could be an expression of difficult cerebrospinal fluid dynamics. The minimal right shift of the midline structures remains substantially unchanged, as well as the initial evidence of uncal herniation. There are no further findings of pathological significance; in particular, there are no significant diffuse or focal parenchymal sign alterations, nor are there other intra- or extra-axial lesions with mass effect or areas of pathological enhancement.
During the neurological check-up on the same day, the patient and his wife denied episodes of even partial epileptic seizures or moments of loss of contact and episodes of paroxysmal aphasia. Furthermore, partial residual right hemisyndrome and partial expressive aphasia were observed. Relatives also reported the appearance of sleepiness and scarce ideomotor initiative. In the same report, it is noted that the patient presented an allergic reaction during anticoagulation therapy with heparin for deep venous thrombosis, which was resolved even without identifying the allergen. It is also noted that the patient never had an electroencephalogram, not even during his recent hospital stay.
Finally, regarding treatment, it was found that the patient was initially taking 150 mg per day of Phenobarbital, as prescribed in the hospital, and a progressive shift to Levetiracetam was advised instead (through agreement with the treating oncologist) in anticipation of the eventuality of changing the chemotherapeutic agent with the possibility of introducing hepatic inducers not compatible with Gardenal.

Expert's Opinion

I have reviewed the notes provided and agree that they are consistent with an aggressive high-grade tumor. Given the patient's age, history, and pathology data, I would recommend the following given the diagnosis of anaplastic astrocytoma and information noted above.
1. Do you confirm the treatment in place?
There was no clear recommendation in the notes I reviewed. My suggestions are:
-       Would consider treatment with standard of care drug temozolomide first before moving to more experimental options below:
Yung WK, Prados MD, et al. Multicenter phase II trial of temozolomide in patients with
anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group. J Clin Oncol. 1999 Sep;17(9):2762-71. Erratum in: J Clin Oncol 1999
Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96.
-       Would recommend a Brain Tumor Center locally that has clinical trial options to try investigational agents such as below or can be used off-label by local oncologist if possible.
-       AVASTIN (bevacizumab) + chemotherapy are the best option currently. A large phase - II trial finished recently and the data is positive and available soon. But other earlier trials have already shown benefit as referenced below.
Vredenburgh JJ, Desjardins A, et al, Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res. 2007 Feb 15;13(4):1253-9.
-       Can also consider Tarceva + rapamycin
Doherty L, Gigas DC, Kesari S, Drappatz J, Kim R, Zimmerman J, Ostrowsky L, Wen PY.
Pilot study of the combination of EGFR and mTOR inhibitors in recurrent malignant gliomas.
Neurology. 2006 Jul 11;67(1):156-8.
-       Can also consider Gleevec+ hydrea
Desjardins A, Quinn JA, Vredenburgh JJ, Sathornsumetee S, Friedman AH, Herndon JE, McLendon RE, Provenzale JM, Rich JN, Sampson JH, Gururangan S, Dowell JM, Salvado A, Friedman HS, Reardon DA. Phase II study of imatinib mesylate and hydroxyurea for recurrent grade III malignant gliomas. J Neurooncol. 2007 May;83(1):53-60. Epub 2007 Jan 24.
Kesari S, Ramakrishna N, Sauvageot C, Stiles CD, Wen PY. Targeted molecular therapy of malignant gliomas. Curr Oncol Rep. 2006 Jan;8(1):58-70.
2. Is it possible to consider surgical intervention?
unlikely to be help for this particular patient based on location and likely hood that the
surgeon will not achieve a gross total resection, if patient has symptoms of mass effect or concern that either the imaging represents necrosis or progression to glioblastoma then reasonable to consider reresection if safe.
3. Which are the Centers of Excellence in Italy?
There are several physicians/centers that I am aware of that have good reputations:
-       Alba A. Brandes, Department of Medical Oncology, Azienda Unità Sanitaria Locale Bellaria-Maggiore, Bologna, Italy.
-       Riccardo Soffietti;Division of Neuro-oncology, Departments of Neuroscience and Oncology, University and San Giovanni Battista Hospital, Torino, Italy
-       Department of Neuro-oncology, Istituto Nazionale Neurologico C. Besta, Milan, Via Celoria 11, Milan, Italy.
There maybe others closer to you location.
 4. Prognosis?
For patients with recurrent disease, the prognosis is guarded and best to seek treatments at academic centers where clinical trials are performed to give patient better options.
All of these recommendations have to be taken in context of functional status and balancing quality of life.