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Paul Van Houtte
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MS 13 - How to Deal with CNS Metastases (ID 535)
- Event: WCLC 2017
- Type: Mini Symposium
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:Martin Schuler, Nir Peled
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 502
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MS 13.02 - SBRT vs. WBRT (ID 7702)
11:15 - 11:30 | Presenting Author(s): Paul Van Houtte
- Abstract
- Presentation
Abstract:
The management of brain metastases remains a challenging issue due to the detrimental impact on the patient quality of life and the wide range of clinical situations. The question is not a local treatment or WBRT but when and how to use the different modalities for each patient. Survival, an endpoint often used, is probably not the best way to evaluate the local efficacy: most patients will died from progressive extracranial disease. The brain tumor control (local or freedom from new brain metastases) is a better way to assess the impact of WBRT or SBRT. Another major problem is the great heterogeneity of the primary tumors and clinical situations. First, we should remember that most patients are not candidate for a local treatment (SBRT or surgery (S)) due to the number of lesions, locations, performance status, meningeal infiltration…and WBRT remains the standard treatment if a brain irradiation is needed. For patients with an “oligo metastatic disease”, many studies have clearly showed the superiority of a form of local treatment (S or SBRT) compared to WBRT at least in term of progression or control at the primary brain site (table1)(1-5). Another issue is to control the disease within the brain: new brain metastases are very common. WBRT has been tested either after S or SBRT to prevent the development of those new lesions: indeed adding WBRT let to a better brain tumor control but this did not translate in any major survival benefit. One major drawback of WBRT is its possible toxicity: the impact on the quality of life, the neurocognitive toxicity, the fatigue and the hair loss. In the EORTC trial, WBRT had a transitory negative impact on the physical or cognitive functioning and more fatigue in the early period of observation compared to the group of patients in the observation arm (6.). A current approach is to follow the patient after SBRT and in case of relapse to propose a salvage treatment which may be a new course of SBRT or even WBRT. Another question was to improve the local control after S adding SBRT. Postoperative SBRT has been proposed and several retrospective studies have shown the feasibility results. Two recently published randomized trials have compared postoperative SBRT to either WBRT or observation. The two main conclusions were less cognitive deterioration with SBRT compared to WBRT( 15% vs 48%) and less local relapse at the primary site compared to no treatment (at 1 year 43% vs 72%) but no difference in overall survival (4,5). An intriguing observation was the better local control at one year after postoperative WBRT compared to SBRT (4). Is there a group of patients benefiting from WBRT? In a new analysis of the Aoyama trial, patients with NSCLC were divided according to a graded prognostic assessment: a statistically significant benefit was observed only in the favorable group with a 6 months gain in median survival (7). A similar observation was reported in the RTOG trial testing the role of adding SBRT to WBRT with a median survival of 14 vs 21 months (8). Is it possible to reduce WBRT toxicity? The hippocampus region play an important role in the preservation of the neurocognitive functions: techniques have been developed to spare the hippocampus region keeping the dose below 7 Gy with a better quality of life and a very low risk of new brain metastases occurring in this spared regions (9). This approach should be tested in large scale phase III trial. Last but not least, the timing of the treatment should be individualized based on the patient needs, and in asymptomatic patients, SBRT may be safely postponed if a systemic treatment is to be administered.
· Estimated from figures References 1.Aoyama H., Tago M., Shirato H. for the Japanese Radiation Oncology study Group 99-1 (JROSG 99-1) investigators Stereotactic radiosurgery with or without whole-brain radiotherapy for brain metastases. Secondary analysis of the JROSG-99 randomized clinical trial JAM Oncol. 2015; 1: 457-464 2.Kocher M., Soffietti R., Abacioglu U., et al Adjuvant whole-brain radiotherapy versus observation after surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J.Clin.Oncol. 2011; 29:131-141 3.Andrews D.W., Scott C.B., Sperduto D.W. et al Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: Phase III results of the RTOG 9508 randomised trial Lancet 2004; 363:1665-72 4.Brown PD, Ballman KV, Cerhan JH,et al Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial.Lancet Oncol. 2017 Jul 4. pii: S1470-2045(17)30441-2. doi: 10.1016/S1470-2045(17)30441-2. [Epub ahead of print] 5.Mahajan A, Ahmed S, McAleer MF, et al Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial. Lancet Oncol. 2017 Jul 4. pii: S1470-2045(17)30414-X. doi: 10.1016/S1470-2045(17)30414-X. [Epub ahead of print) 6.Soffietti R., Kocher M., Abacioglu U., et al A European Organiszation for Research and Treatment of Cancer phase III trial of adjuvant whole-brain radiotherapy versus observation after surgical resection of one to three cerebral metastases: quality of life results J.Clin.Oncol. 2011; 31:65-72 7.Aoyama H., Tago M., Shirato H. et al Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial JAMA 2006; 295: 2483-91 8.Sperduto P.W., Shanley R., Luo X., et al Secondary analysis of RTOG 9508, a phase 3 randomized trial of whole-brain radiation verus WBRT plus stereotactic radiosurgery in patients with 1-3 brain metastases; poststratified by the graded prognostic assessment (GPA). Int.J.Radiat.Biol.Phys. 2014; 90: 526-531 9.Gondi V., Hermann B.P., Mehta M.P., Tome W.A. Hippocampal dosimetry predicts neurocognitive function impairment after fractionated stereotactic radiotherapy for benign or low-grade adult brain tumors. Int. J. Radiat. Oncol. Biol. Phys. 2012 ; 83 : 487–93Authors Treatment Evaluation Time Local Control Brain Tumor Control Aoyama Kocher Andrews Brown Mahajan SBRT SBRT+WBRT Surgery Surg+WBRT SBRT SBRT+WBRT WBRT WBRT+SBRT Surg+WBRT Surg +SBRT Surg SURG.SBRT 1 Y 2 Y 1Y 1Y 1 Y 72% 88% 41% 73% 69% 81% 60% 74% 78% 55% 45% 72% 23% 53% 58% 77% 52% 67% 51% 62% 69% 32% 33% 43%
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