Algehele radiotherapie - bestraling naast stereotactische bestraling voor uitzaaiingen in de hersenen vanuit andere vormen van kanker dan primaire hersentumoren veroorzaakt ernstige leer- , geheugen

11 oktober 2009: Bron: The Lancet

Agehele radiotherapie - bestraling naast stereotactische bestraling - Gamma Knife voor uitzaaiingen in de hersenen vanuit andere vormen van kanker dan primaire hersentumoren veroorzaakt ernstige geheugen en concentratieproblemen en heeft geen enkel effect op overall overleving in vergelijking met alleen radiotherapie - bestraling naast operatie. De studie is stopgezet omdat al snel duidelijk werd dat de groep die de combinatiebehandeling kreeg ernstige problemen kreeg met geheugen- en concentratieverlies. Plus dat de eerste vier maanden in de combinatiegroep 8 patienten stierven tegenover 4 in de groep die alleen bestraling kreeg. Op respectievelijk 30 patienten in de combinatiegroep van stereotactische bestraling plus algehele bestraling en 28 in de groep die alleen stereotactische bestraling kreeg. De onderzoekers raden met klem aan om mensen met niet meer dan 3 metastases alleen met stereotactische bestraling te behandelen en geen algehele bestraling toe te voegen.

At 4 months, 4 patients (13%) in the radiosurgery-alone group had died, compared with 8 (29%) in the combination group. The researchers also observed that the median and 1-year overall survival was higher for patients in the radiosurgery-alone group than for those in the combination group (median survival, 15.2 vs 5.7 months; overall survival, 63% vs 21%; P = .003).

However, local tumor control at 1 year was higher for those in the combination group (100% vs 67%; P = .012), as was the distant brain tumor control rate (73% vs 45%; P = .02) and 1-year freedom from central nervous system recurrence (73% vs 27%; P = .0003).

1: Lancet Oncol. 2009 Oct 2. [Epub ahead of print]

Links

Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial.

Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, Arbuckle RB, Swint JM, Shiu AS, Maor MH, Meyers CA.

Department of Radiation Oncology, The University of Texas, M D Anderson Cancer Center, Houston, TX, USA.

BACKGROUND: It is unclear whether the benefit of adding whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) for the control of brain-tumours outweighs the potential neurocognitive risks. We proposed that the learning and memory functions of patients who undergo SRS plus WBRT are worse than those of patients who undergo SRS alone. We did a randomised controlled trial to test our prediction.

METHODS: Patients with one to three newly diagnosed brain metastases were randomly assigned using a standard permutated block algorithm with random block sizes to SRS plus WBRT or SRS alone from Jan 2, 2001, to Sept 14, 2007. Patients were stratified by recursive partitioning analysis class, number of brain metastases, and radioresistant histology. The randomisation sequence was masked until assignation, at which point both clinicians and patients were made aware of the treatment allocation. The primary endpoint was neurocognitive function: objectively measured as a significant deterioration (5-point drop compared with baseline) in Hopkins Verbal Learning Test-Revised (HVLT-R) total recall at 4 months. An independent data monitoring committee monitored the trial using Bayesian statistical methods. Analysis was by intention-to-treat. This trial is registered at www.ClinicalTrials.gov, number NCT00548756.

FINDINGS: After 58 patients were recruited (n=30 in the SRS alone group, n=28 in the SRS plus WBRT group), the trial was stopped by the data monitoring committee according to early stopping rules on the basis that there was a high probability (96%) that patients randomly assigned to receive SRS plus WBRT were significantly more likely to show a decline in learning and memory function (mean posterior probability of decline 52%) at 4 months than patients assigned to receive SRS alone (mean posterior probability of decline 24%). At 4 months there were four deaths (13%) in the group that received SRS alone, and eight deaths (29%) in the group that received SRS plus WBRT. 73% of patients in the SRS plus WBRT group were free from CNS recurrence at 1 year, compared with 27% of patients who received SRS alone (p=0.0003). In the SRS plus WBRT group, one case of grade 3 toxicity (seizures, motor neuropathy, depressed level of consciousness) was attributed to radiation treatment. In the group that received SRS, one case of grade 3 toxicity (aphasia) was attributed to radiation treatment. Two cases of grade 4 toxicity in the group that received SRS alone were diagnosed as radiation necrosis.

INTERPRETATION: Patients treated with SRS plus WBRT were at a greater risk of a significant decline in learning and memory function by 4 months compared with the group that received SRS alone. Initial treatment with a combination of SRS and close clinical monitoring is recommended as the preferred treatment strategy to better preserve learning and memory in patients with newly diagnosed brain metastases.

FUNDING: No external funding was received.

PMID: 19801201 [PubMed - as supplied by publisher]

Een paar citaten uit een artikel in Medscape over deze studie van onderzoeksleider Eric Chang MD:

October 7, 2009 — ........"In our study, patients who received radiosurgery plus whole-brain radiation were at twice the risk of developing learning and memory problems at 4 months patients getting radiosurgery alone," said lead study author Eric Chang, MD, associate professor in the Department of Radiation Oncology at the University of Texas MD Anderson Cancer Center in Houston.

In fact, the trial was stopped early by the data monitoring committee because there was a high probability (96%) that patients who were randomized to receive stereotactic radiosurgery plus whole-brain radiation therapy were significantly more likely to show a cognitive decline.

"Giving whole-brain radiation therapy in conjunction with stereotactic radiosurgery is highly controversial in the United States right now," said Dr. Chang. "Some might argue it is the standard treatment, but there is no consensus on this point. I would say there is a fair proportion of centers that do it, but there are many centers that do not."

Dr. Chang added that this study provides the strongest evidence to date that supports giving radiosurgery alone with close clinical monitoring as the preferred treatment strategy for patients newly diagnosed with a limited number of brain metastases. "We advocate the judicious and appropriate use of surgery, radiosurgery, or whole-brain irradiation only if needed for any recurrences that may develop later on in the brain," he told Medscape Oncology.

I would advocate . . . using stereotactic surgery alone.

"I would advocate that physicians and their patients who are interested in preserving cognitive function and memory strongly consider using stereotactic surgery alone with close clinical monitoring in the initial management of their brain metastases," Dr. Chang said.

"Our strategy is consistent with the trend toward personalized medicine — tailoring therapies to the patient and their disease rather than applying a 'one size fits all' approach of giving whole-brain radiation therapy to all patients with brain metastases," he added.

Gamma Knife, bestrlaing, radiotehrapie