NcXHF

RADIOTHERAPY AND RADIOSURGERY EVIDENCE IN BRAIN METASTASES
ical models. 28,29 In a prospective human study, a strong association
with increasing hippocampal radiation dose and
neurocognitive dysfunction was demonstrated. 30 Intensitymodulated
radiotherapy can be used to conformally avoid
the hippocampal neural stem cell compartment during
WBRT (HA-WBRT). This hypothesis was tested in a singlearm
phase II study of HA-WBRT for brain metastases that
used a prespecifıed comparison with a historic control of patients
treated with WBRT without hippocampal avoidance
(RTOG 0933). 31 The primary endpoint was change in
HVLT-DR measured at 4 months. The historic control
(without hippocampal avoidance) resulted in a 30% mean
relative loss in HVLT-DR from baseline to 4 months. The
actual observed mean relative decline in HVLT-DR from
baseline to 4 months was, in fact, only 7.0%, which was signifıcantly
lower than the historic control of 30% (p 0.0003).
No decline in quality-of-life scores up to 6 months was
seen. 31 These observations now form the basis of two newer
phase III trials, NRG CC 001 and CC 002.
CONCLUSION
The management of brain metastases has evolved over the
years from palliation to an era of exciting active research. Local
therapies (WBRT, SRS) are important modalities in the
management of brain metastases. Areas of active investigation
include techniques to preserve neurocognitive function
with radiotherapy. The optimal management strategy for
these patients involves a multidisciplinary approach that accounts
for individual characteristics of both the patient and
the tumor. A number of ongoing prospective clinical trials
will help further defıne the role and application of WBRT and
SRS in the management of brain metastases.
Disclosures of Potential Conflicts of Interest
Relationships are considered self-held and compensated unless otherwise noted. Relationships marked “L” indicate leadership positions. Relationships marked “I” are those held by an immediate
family member; those marked “B” are held by the author and an immediate family member. Institutional relationships are marked “Inst.” Relationships marked “U” are uncompensated.
Employment: None. Leadership Position: Minesh P. Mehta, Pharmacyclics. Stock or Other Ownership Interests: Minesh P. Mehta, Pharmacyclics.
Honoraria: Minesh P. Mehta, Ca Progress, Elekta, Research to Practice, Serono Foundation. Manmeet S. Ahluwalia, Elekta, Sigma-Tau. Consulting or
Advisory Role: Minesh P. Mehta, Abbvie, Best Medical Opinion, BMS, Celldex, GLG, MedaCorp, Medical Director Solutions, Novelos, Novocure, Philips
Healthcare, Roche/Genentech, Strategic Edge, US Oncology Ask The Expert. Manmeet S. Ahluwalia, Genentech/Roche, Monteris Medical, Novocure. Speakers’
Bureau: Manmeet S. Ahluwalia, Sigma-Tau. Research Funding: Minesh P. Mehta, Novelos (Inst), Novocure (Inst). Manmeet S. Ahluwalia, Boehringer
Ingelheim, Lilly/ImClone, Novartis, Novocure, Spectrum Pharmaceuticals, TRACON Pharma. Patents, Royalties, or Other Intellectual Property: None.
Expert Testimony: None. Travel, Accommodations, Expenses: Manmeet S. Ahluwalia, Elekta. Other Relationships: None.
References
1. Chao JH, Phillips R, Nickson JJ. Roentgen-ray therapy of cerebral metastases.
Cancer. 1954;7:682-689.
2. Borgelt B, Gelber R, Larson M, et al. Ultra-rapid high dose irradiation
schedules for the palliation of brain metastases: fınal results of the fırst
two studies by the Radiation Therapy Oncology Group. Int J Radiat Oncol
Biol Phys. 1981;7:1633-1638.
3. Patchell RA, Tibbs PA, Regine WF, et al. Postoperative radiotherapy in
the treatment of single metastases to the brain: a randomized trial.
JAMA. 1998;280:1485-1489.
4. Sanghavi SN, Miranpuri SS, Chappell R, et al. Radiosurgery for patients
with brain metastases: a multi-institutional analysis, stratifıed by the
RTOG recursive partitioning analysis method. Int J Radiat Oncol Biol
Phys. 2001;51:426-434.
5. Andrews DW, Scott CB, Sperduto PW, 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;363:1665-1672.
6. Aoyama H, Shirato H, Tago M, et al. Stereotactic radiosurgery plus
whole-brain radiation therapy vs stereotactic radiosurgery alone for
treatment of brain metastases: a randomized controlled trial. JAMA.
2006;295:2483-2491.
7. Kocher M, Soffıetti R, Abacioglu U, et al. Adjuvant whole-brain radiotherapy
versus observation after radiosurgery or surgical resection of
one to three cerebral metastases: results of the EORTC 22952-26001
study. J Clin Oncol. 2011;29:134-141.
8. Chang EL, Wefel JS, Hess KR, et al. Neurocognition in patients with
brain metastases treated with radiosurgery or radiosurgery plus wholebrain
irradiation: a randomised controlled trial. Lancet Oncol. 2009;10:
1037-1044.
9. Hunter GK, Suh JH, Reuther AM, et al. Treatment of fıve or more brain
metastases with stereotactic radiosurgery. Int J Radiat Oncol Biol Phys.
2012;83:1394-1398.
10. Mohammadi AM, Recinos PF, Barnett GH, et al. Role of gamma knife
surgery in patients with 5 or more brain metastases. J Neurosurg. 2012;
117 (Suppl):5-12.
11. Yamamoto M, Serizawa T, Shuto T, et al. Stereotactic radiosurgery for
patients with multiple brain metastases (JLGK0901): a multiinstitutional
prospective observational study. Lancet Oncol. 2014;15:
387-395.
12. Kondziolka D, Kalkanis SN, Mehta MP, et al. It is time to reevaluate the
management of patients with brain metastases. Neurosurgery. 2014;75:
1-9.
13. Choi CY, Chang SD, Gibbs IC, et al. Stereotactic radiosurgery of the
postoperative resection cavity for brain metastases: prospective evaluation
of target margin on tumor control. Int J Radiat Oncol Biol Phys.
2012;84:336-342.
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