Important Studies Flashcards
Addition of surgery to WBRT?
“Patchell I” University of Kentucky. Patchell et al, NEJM, 1990. Single brain mets→ Surgery + WBRT 36 Gy vs.
Biopsy + WBRT 36 Gy. “
Surgery added to WBRT improved survival and LC
Median OS 40 wks vs. 15 wks; LR 20% vs. 52%
WBRT dose escalation?
RTOG 6901 & 7361: “Borgelt et al, IJROBP, 1980. Borgelt et al, IJROBP, 1981”. “WBRT dose escalation:30 Gy/ 10 fx → 30/15 → 40/15 → 40/20; 20/5 → 30/10 → 40/15”.
There is no difference in symptom response or OS between these RT schedules for WBRT. In some populations, 40/15 seemed to trend to better OS.
Hippocampal avoidance+memantine?
NRG-CC001: Brown et al, JCO, 2020. brain mets→WBRT 30 Gy/10 fx vs. →hippocampal avoidance IMRT WBRT 30 Gy/10 fx with memantine in both arms. Hippocampal avoidance RT leads to improved cognitive function.
WBRT vs. supportive care?
QUARTZ. Mulvenna et al, Lancet, 2016. “NSCLC with brain metastasis unsuitable for surgery or SRS →WBRT 20 Gy/5 fx vs. →no RT. Primary endpoint: QALYs Supportive care and dex in both arms.
WBRT for palliation of brain mets is noninferior to observation in QALY outcomes in these poor prognosis patients. On subanalysis OS favors WBRT for ≥5 mets or age <60.
Addition of WBRT to SRS/surgery?
EORTC 22952-26001. “Kocher et al, JCO, 2011
Soffietti et al, JCO, 2013”. 1-3 brain mets <3.5 cm, controlled extracranial disease, PS 0-2. “Surgery or SRS→
obs vs. WBRT 30 Gy”. After surgery or SRS in limited mets, WBRT reduces LR but does not improve QOL or OS.
Addition of WBRT to SRS?
JSROG. “Aoyama et al, JAMA, 2006. Aoyama et al, JAMA Oncol 2015”. 1-4 brain mets <3cm→SRS vs. SRS+WBRT 30 Gy/10 fx. SRS dose 18-25 Gy for SRS alone. Dose reduced 30% if with WBRT. MMSE used to measure cognitive function”. SRS alone without WBRT in limited mets resulted in increased brain tumor recurrence but no change in OS or neurologic death.
MDACC. Chang et al, Lancet Oncol, 2009. 1-3 brain mets→ SRS vs. SRS+WBRT 30 Gy/12 fx. Primary endpoint: neuro function per HVLT-R. Adding WBRT to SRS in limited mets results in worse neuro decline and worse OS.
Alliance N0574. Brown et al, JAMA, 2016. 1-3 brain mets→ SRS vs. SRS+WBRT 30 Gy/12 fx. SRS dose 18-22 Gy in SRS+WBRT and SRS dose 20-24 Gy for SRS alone. SRS without WBRT in limited mets results in less neuro decline. Tumor reccurence is increased somewhat without WBRT but without change in OS.
Addition of SRS boost to WBRT?
RTOG 9508. "Andrews et al, Lancet, 2004 Sperduto et al, IJROBP, 2014". 1-3 mets→ WBRT 37.5 Gy vs. →SRS+WBRT. SRS dose per RTOG 9005: 24 Gy size ≤2.0 cm 18 Gy size >2 to ≤3cm 15 Gy size >3 cm Adding an SRS boost to WBRT in limited mets improves LC but not OS
SRS dose escalation?
RTOG 9005. Shaw et al, IJROBP, 2000. Recurrent primary or recurrent brain tumors s/p prior WBRT
Phase I Dose escalation in 3 Gy increments. Starts at:
18 Gy for ≤2 cm
15 Gy for 2-3 cm
12 Gy for 3-4 cm
Grade 3-5 toxicity defined as limiting.
All had previous WBRT (range 30-60 Gy). LINAC and GammaKnife allowed. Dose to 50-90% isodose line.
Max tolerated doses in SRS for brain mets: 24 Gy for ≤20 mm, 18 Gy for 21-30 mm, and 15 Gy for 31-40 mm.
SRS to multiple lesions?
Katsuta Hospital Mito Gamma House, Hitachi-naka, Japan. “Yamamoto et al, Lancet Oncol, 2014
Yamamoto et al, IJROBP, 2017”. 1-10 brain metastases. “Prospective noninferiority SRS 2-4 lesions cohort
vs. SRS 5-10 lesions cohort. SRS alone to 5-10 brain metastasis is noninferior to 2-4 lesions.
SRS single vs. multi fx
Mount Sinai, NY. Lehrer et al, IJROBP, 2019. “Meta-analysis of 24 studies of single and multi fx SRS to brain mets. Evaluates radiation necrosis and LC. Various doses and fractionation regimens used.
In tumors size 4-14 cc, about 2-3 cm diameter, there is a reduction in radiation necrosis with multi fx RT.
There are changes in LC that did not reach statistical significance. Various techniques and assessments would have been used across studies. Randomized and prospective trials are warranted.
SRS for post op cavity vs. WBRT?
N107C/ CEC.3/ RTOG 1270. “Brown et al, Lancet Oncol, 2017, Trifiletti et al, ASTRO, 2019”. “1-4 brain metastases and resection of 1 lesion. STR allowed (77%% had single met, ~10% STR). Resection cavity <5 cm and unresected lesions ≤3.0 cm”. “→SRS to cavity vs. WBRT to 30 or 37.5 Gy. “SRS alone leads to unchanged OS compared to WBRT alone. WBRT has better LC. QOL is improved with SRS. When comparing 37.5 Gy to 30 Gy, 37.5 Gy led to more toxicity. There was some trend to benefit in LC, cranial control, and OS, but not significant.”
SRS for post op cavity STR vs. WBRT?
JCOG0504. Kayama et al, JCO, 2017.”1-4 brain metastasis and resection of all, GTR or STR (73% had single met). One lesion >3 cm allowed”. “Resection of all brain mets →SRS to cavity for STRs, observe GTRs (termed ““salvage SRS””) vs. WBRT 37.5 Gy. 40% in SRS arm had STR and SRS; 60% had GTR and obs. SRS doses: 24 Gy for ≤4 cc, 18 Gy for >4 cc”. SRS for STR only in resected brain mets is noninferior compared to WBRT in OS. However LR is increased.
SRS for post op cavity?
MDACC. Mahajan et al, Lancet Oncol, 2017. “1-3 brain metastases and GTR of ≥1 lesion (~62% had single met). Resection cavity ≤4 cm and unresected lesions ≤3 cm→SRS to cavity vs. Obs to cavity . Unresected lesions treated with SRS in both arms. SRS improves LC compared to observation in resected brain mets. OS and neurologic death are unchanged.
GPA?
University of Minnesota. “Sperduto et al, IJROBP, 2008
Sperduto et al, JCO, 2012”. brain metastases. Evaluation of patients from 11 institutions. Prognostic factors for brain metastasis vary by diagnosis.
RPA?
RTOG. Gaspar et al, IJROBP, 1997. Recursive partitioning analysis.
Class 1: KPS≥70, <65yo, brain is only site of mets, controlled primary. 7.1 mos
Class 2: all others 4.2 mos
Class 3: KPS<70. 2.3 mos”
