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| Jin-Ming Yu, MD PhD Professor Director, Radiotherapy Department Cancer Hospital of Shandong Province Academician, Chinese Academy of Engineering Photo:SD-Cancer.com |
Introduction
LBA4: A multicenter phase III clinical trials is sponsored by the NCI to reevaluate the efficacy of Whole brain Radiation therapy(WBRT) in addition to SRS(Radio Surgery)treatment for patients with 1-3 small metastatic carcinomas. The result showed that decline cognitive function(especially in immediate recall, memory and verbal fluency) was more frequent with WBRT group, and did not improve overall survival.
So the researchers recommend, close monitoring after SRS treatment without WBRT should be an option, for newly diagnosed brain metastases cancer patients.
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| ASCO 2015 Conference Chicago, IL Photo: Oncology Frontier |
The onsite discussion
Andrew B. Lassman, MD, Columbia University Center"N0574 study found that nervous system damage can be up to 12 months post WBRT, and WBRT's damage on cognitive function as side effects may be worse than brain metastasis, yet many studies in the past showed the opposite results.
Explanations
For this seemingly contradictory phenomenon, possible explanations are as follows.
Progression percentages of brain metastases post SRS were different between the trials, with around 50% in the study of N0574, while in the previous study is 73%~78% (such as JROSG 99-1, EORTC 22952-26001 trial) .
Incidence of brain metastases after SRS is very low, long-term follow-up is needed. All the study didn't use > 3 months of cognitive decline as the primary study end point, also the sample sizes were small (N0574:34 cases; JROSG 99-1; MDGS: 9).
Different assessment tools were used in the trials. And finally, you need to pay special attention to the location of the brain metastasis, which is one of the influence factors to damage the nervous system."
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| ASCO 2015 meeting Chicago, IL Photo: Oncology Frontier |
Interpretation
"Therefore, from N0574's conclusion, we can have another kind of interpretation: additional WBRT can improve survival in particular group of patients.
If you avoid WBRT, recurrence brain metastases still may affect cognitive function in patients. Of course N0574 studies suggest that, in comparison, WBRT may lead to worse results.
WBRT may be used in selected patients, such as with life-threatening brain metastases."
Dr. Jin-Ming Yu's comment
For 1 ~ 3 brain metastases, to do SRS, or to do auxiliary WBRT, is an age-old topic, and there are evidences from each side.
N0574 research results suggest that WBRT improved local control, but no help for OS. This is expected.
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| ASCO 2015, Poster seciton McCormick Place, Chicago Photo: Oncology Frontier |
The researchers vs the discussants
The researcher's attitude is very clear-auxiliary WBRT not recommended, yet people's attitude who participated in the debate seems to be the opposite, tend to do auxiliary WBRT, and listed the advantages of WBRT.
Individualized consideration
I think, in clinical practice, the choice of brain metastasis treatment should be taken into with multiple factors (patients, disease, treatment), and should be individualized choice.
For example, an older patients, with poor prognosis tumor type, bad primary tumor control, the principle of brain metastasis treatment is to use low tolerance (only metastases) choice; However, if the patient is young, in general good condition, and with good prognosis tumor type, in order to avoid increased brain metastatic lesions and secondary transfer, after SRS if the patient's general condition is good, can consider additional WBRT.
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| ASCO 2015 McCormick Place, Chicago Photo: Oncology Frontier |
Other alternatives
In addition, besides WBRT, there are other alternatives in addition to SRS in the treatment of brain metastases: drugs, such as molecular targeted drugs, immune treatment; Special radiation pattern, WBRT with hippocampus proteciton(HA - WBRT); some chemo drugs can have protection combined with radiation therapy.
Conclusion
In conclusion, either WBRT or brain metastases recurrence, may be the cause of functional deterioration, so we should have other alternative methods.
References:
1. Paul D. Brown etc. NCCTG N0574 (Alliance): A phase III randomized trial of whole brain radiation therapy (WBRT) in addition to radiosurgery (SRS) in patients with 1 to 3 brain metastases J Clin Oncol 33, 2015 (suppl; abstr LBA4)
2. 【ASCO 2015】独家：于金明院士点评大会报告LBA4 2015-06-02 中国医学论坛报今日肿瘤 微信公众号
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