Radiation therapy for melanoma brain metastases: a systematic review

Thompson, John F.; Williams, Gabrielle J.; Hong, Angela M.

doi:10.2478/raon-2022-0032

Figures & Tables

Flowchart of search findings, exclusions and number of included studies.

(A) Risk of bias assessments for randomised controlled trials evaluating radiation therapies in patients with melanoma brain metastases. (B) Quality assessment of cohort studies of patients with melanoma brain metastases treated with radiation therapy.

Patient characteristics within treatment group for the 51 studies that reported baseline characteristics

Treatment group		Age in years	Proportion of patients
Treatment group		Age in years	Males	Asymptomatic	With single brain metastasis	With controlled primary disease
	Median	53.0	63.8%	i11.5%, i32.2%	26.6%	29.0%
WBRT alone	IQR	49.0–55.8	42.5–73.7 %	NA	18.5–48.6%	13.9–47.8%
	N studies(pts)	10 (295)	13 (496)	2 (85)	7 (339)	10 (329)
	Median	60.2	66.7%	66.8%	54.8%	32.2%
SRS alone	IQR	56.25–62.25	54.0–76.3%	59.65–78.79%	41.19–61.22	26.16–36.32%
	N studies(pts)	9 (444)	12 (822)	4 (359)	9 (706)	8 (669)
WBRT and any of SRS, surgery,	Median	53.0	63.4%		51.7%	45.9%
	IQR	47.00–58.75	51.64–73.88%		40.72–72.91%	30.18–68.06%
chemotherapy, non-contemp	N studies(pts)	5 (243)	6 (266)		4 (223)	6 (262)
SRS and any of;	Median	56.9	59.1%	65.4%	38.8%	24.0%
surgery, WBRT, chemotherapy,	IQR	52.5 – 59.25	54.82 – 68.04%	51.28 – 66.38%	30.11 – 51.74%	17.56 – 39.70%
non-contemp	N studies(pts)	17 (1127)	20 (1838)	5 (953)	16 (1697)	16 (1660)

Pooled outcome results for studies of radiation treatments

Treatment	Groups	Median survival		1-year survival rate, %		1-year local control rate		6-mo new brain lesion rate		Serious adverse events
Treatment	Groups									Serious adverse events
		Studies (Patients)	Months (IQR)	Studies (Patients)	% (IQR)	Studies (Patients)	% (IQR)	Studies (Patients)	% (IQR)
WBRT vs. WBRT + Surgery
Non-random,	WBRT	11 (980)	4.0 (3.0, 4.0)							Not reported
comparative	WBRT+Surg	11 (439)	11.0 (8.8,11.8)
All studies	WBRT	26 (2185)	3.5 (2.4, 4.0)	7 (189)	9.0 (0.0, 22.5)	1 (74)	5.5 (0.0,			Post-op death;
	WBRT+Surg	16 (619)	11.0 (7.8, 12.0)	1 (19)	i41.0	0	12.0)			2% (1 study),
										Hemorrhage;
										3/72 lesions (1 Study)
WBRT vs. Surgery
Non-random,	WBRT	5 (699)	3.9 (3.6, 5.0)							-
comparative	Surgery	5 (234)	9.8 (7.6, 16.5)							Gr3 tox; 3/39 (1 study)
	Surgery	9 (359	8.7 (6.2, 10.4)	1 (16)	i36.0					Post-op death;
All studies										2% (1 Study)
WBRT vs. SRS
Non-random,	WBRT	3 (931)	4.1 (3.2, 5.6)							-
comparative	SRS	3 (980)	8.8 (7.2, 11.4)							Hemorrhage; 4/56
	SRS	8 (1188)	7.5 (6.7, 9.0)	6 (330)	35.5 (20.8, 47.8)	4 (260)	76.0			lesions (1 study)
All studies							(62.8,			(SRS-GK)
					i26.0		88.5)
	SRS-GK	5 (208)	7.0 (5.6, 7.8)	1 (83)
SRS Type	SRS-LA	0	-
	SRS-NS	3 (980)	8.8 (7.2, 11.4)
WBRT vs. WBRT +
Chemotherapy
Non-random,	WBRT	4 (148)	2.5 (1.0, 4.2)	0	-					Gr3 tox; 3/39 (1 study)
comparative	WBRT +Chemo	4 (62)	5.5 (4.0, 6.0)	1 (7)	i0.0
										Leukopenia; 2/8
All studies	WBRT+Chemo	6 (137)	4.3 (2.8, 6.0)	2 (15)	i0.0, i37.0	0	-	0	-	(1 study), Toxicity;
										9/14 (1 study)
SRS vs. WBRT+SRS										Swelling
Non-random,	SRS	5 (881)	7.0 (6.0, 8.1)	1 (83)	i26.0					requiring surgical
comparative	WBRT+SRS	5 (344)	6.5 (5.7, 6.5)	1 (39)	i23.0					decompression;
										3/77 pts (1 study)
	WBRT+SRS	12 (516)	7.0 (6.0, 8.0)	3 (58)	36.0 (29.5, 37.0)	0	-	0	-
All studies										-
WBRT vs. WBRT+SRS
Non-random,	WBRT	4 (337)	3.6 (2.7, 5.0)	1 (59)	i10.0
comparative	WBRT+SRS	4 (197)	7.4 (6.5, 10.7)	1 (8)	i38.0
SRS+ Chemotherapy
Al studies	SRS+Chemo	1 (23)	i6.5	0	-	0	-	0	-	-
	SRS+/- Chemo	7 (580)	7.9 (6.1, 9.9)	2 (358)	i13.2, i27.9	1 (106)	i69.0	1 (106)	i12.0	Hemorrhage; 1/106 pt (1 study), 4/56 lesions (1 study). Radiation necrosis; 1/106 pts (1 study)
SRS + Surgery
All studies	SRS+Surg	4 (200)	13 (9.4, 13.5)	1 (60)	i58.0	1 (34)	i52.0	1 (34)	i32.0	Hemorrhage;
										18% (1 study)
WBRT+ other treatments
All studies	WBRT and any of	47 (2230)	7.2 (4.6, 9.4)	19 (827)	21.4 (13.6, 37.0)	5 (208)	1.0 (0.0,	8 (986)	46.5 (39.8,	WBRT specific;
	surgery, SRS, non-						16.0)		55.5)	Deaths;6/194
	contemp									(1 study), headache; 12/26 (1 study), Toxicity > Gr3; 3/7 (1 study) LeukopeniaGr1-2; 2/9 (1 study) Hemorrhage; 1/20 (1 study)
SRS+ other treatments
All studies	SRS and any of	42 (2702)	8.0 (6.2, 10.9)	35 (2644)	31.0 (25.0, 39.0)	16 (1043)	69.0	10 (1261)	49.0 (42.0,	SRS specific;
	surgery, WBRT, non-						(60.0,		56.0)	Hemorrhage; 14%
	contemp						82.0)			(4 studies, 441 patients) Radiation necrosis; 6.6% (4 studies, 241 patients Seizure-edema-death; 1/55 (1 study) Complications; 6/106 (1 study)

Studies of radiation treatment in patients with melanoma brain metastases

Reference	Year	Country	Treated years	Total patients	Prospective data	Design	Surgery	WBRT	SRS		Non-contemp
Reference	Year	Country	Treated years	Total patients	Prospective data	Design	Surgery	WBRT	LA	GK	Non-contemp
Carella50	1980	US	1971–NS	60	⨯	Treatment cohort	✓	✓			✓
Katz51	1981	US	1971–1980	63	⨯	Treatment cohort	✓	✓
Vlock52	1982	US	1970–1980	46	⨯	Treatment cohort	✓	✓			✓
Byrne43	1983	US	1978–1980	80	⨯	Treatment cohort	✓	✓
Stridsklev53	1984	Norway	1973–1980	39	⨯	Treatment cohort		✓			✓
Choi (A)54	1985	US	1972–1977	194	⨯	Treatment cohort	✓	✓			✓
Choi (B)55	1985	US	1972–1977	59	⨯	Treatment cohort	✓	✓
Ziegler56	1986	US	1972–1984	72	⨯	Treatment cohort	✓	✓
Rate44	1988	US	1980–1987	77	⨯	Treatment cohort	✓	✓			✓
Hagen57	1990	US	1972–1987	35	⨯	Treatment cohort	✓	✓
Stevens38	1992	Australia	1982–1990	129	⨯	Treatment cohort	✓	✓
Somaza58	1993	US	1988–1992	23	⨯	Treatment cohort		✓		✓	✓
Willner59	1995	Germany	1985–1993	30	⨯	Disease cohort	✓	✓			✓
Isokangas40	1996	Finland	1980–1994	60	⨯	Treatment cohort	✓	✓			✓
Skibber60	1996	US	1979–1991	34	⨯	Treatment cohort	✓	✓
Gieger36	1997	US	1992–1994	12	⨯	Treatment cohort	✓	✓	✓
Gupta61	1997	UK	1991–1996	31	⨯	Treatment cohort	✓	✓
Grob62	1998	France	1993–1996	35	⨯	Treatment cohort	✓			✓	✓
Sampson63	1998	US	past years 20	670	⨯	Disease cohort	✓	✓
Seung64	1998	US	1991–1995	55	⨯	Treatment cohort		✓		✓
Lavine65	1999	US	1994–1997	45	⨯	Treatment cohort	✓	✓		✓
Kontsadoulakis66	2000	US	1970–1992	136	⨯	Disease cohort	✓	✓			✓
Ellerhorst67	2001	US	1992–1995	87	⨯	Treatment cohort	✓	✓
Buchsbaum68	2002	US	1994–1998	74	⨯	Disease cohort	✓	✓	✓	✓
Gonzalez- Martinez69	2002	US	1996–NS	24	⨯	Treatment cohort		✓		✓	✓
Mingione70	2002	US	1989–1999	45	⨯	Treatment cohort	✓	✓		✓	✓
Noel71	2002	France	1994–2001	25	⨯	Treatment cohort			✓
Yu72	2002	US	1994–1999	122	⨯	Treatment cohort		✓		✓
Zacest73	2002	Australia	1979–1999	147	⨯	Treatment cohort	✓	✓			✓
Harrison74	2003	US	1990–1997	65	⨯	Treatment cohort	✓	✓
Conill75	2004	Spain	1997–2002	26	⨯	Treatment cohort		✓			✓
Fife37	2004	Australia	1985–2000 (also 1952– 1984)	686 (+ 451)	⨯	Disease cohort	✓	✓
Meier76	2004	Switzerland	1966–2002	100	⨯	Disease cohort	✓	✓	✓	✓	✓
Morris77	2004	UK	1998–2003	102	⨯	Treatment cohort	✓	✓	?	?	✓
Radbill78	2004	US	1996–2001	51	⨯	Treatment cohort	✓	✓		✓
Selek79	2004	US	1991–2001	103	⨯	Treatment cohort	✓	✓	✓
Stone80	2004	US	1989–1999	83	⨯	Disease cohort	✓	✓		✓
Koc81	2005	US	1999–2003	26	⨯	Treatment cohort				✓	✓
Panagiotou82	2005	Greece	1986–2001	64	⨯	Disease cohort	✓	✓			✓
Rhomberg83	2005	Austria	1982–2002	19	⨯	Treatment cohort		✓			✓
Christopoulou84	2006	UK	1998–2004	29	⨯	Treatment cohort	✓	✓		✓
MarquestaGaudy- 85	2006	France	1997–2003	106	⨯	Treatment cohort				✓	✓
Conill86	2007	Spain	1997–2004	37	⨯	Treatment cohort		✓			✓
Mathieu87	2007	US	1987–2005	245	⨯	Treatment cohort	✓	✓		✓
Samlowski32	2007	US	1999–2004	44	⨯	Treatment cohort	✓	✓	✓		✓
Raizer5	2008	US	1991–2001	355	⨯	Disease cohort	✓	✓	?	?	✓
Redmond88	2008	US	1998–2007	59	⨯	Treatment cohort	✓	✓		✓
Carrubba89	2009	US	2002–2007	37	⨯	Disease cohort	✓	✓	?	?
Ahmad90	2010	UK	2001–2009	65	⨯	Treatment cohort	✓	✓
Rades91	2010	Germany	1989–2008	51	⨯	Treatment cohort		✓
Schild92	2010	US	NS	7 (+ 53)	Y+N	Treatment cohort		✓			✓
Staudt93	2010	Germany	1986–2003	265	⨯	Disease cohort	✓	✓	✓		✓
Davies34	2011	US	1986–2004	330	⨯	Disease cohort	✓	✓	?	?
Eigentler94	2011	Germany	1986–2007	672	⨯	Disease cohort	✓	✓	?	?	✓
Liew95	2011	US	1987–2008	333	⨯	Treatment cohort		✓		✓
Skeie96	2011	Norway	1996–2006	77	⨯	Treatment cohort	✓	✓		✓
Zakrzewski97	2011	US	2002–2008	89	⨯	Disease cohort	✓		?	?	✓
Bernard98	2012	US	2004–2010	54	⨯	Treatment cohort	✓		✓
Hauswald33	2012	Germany	2000–2011	87	⨯	Treatment cohort	✓	✓	?	?
Knisely35	2012	US	2002–2010	77	⨯	Treatment cohort		✓		✓	✓
Koay99	2012	US	2005–2011	296	⨯	Disease cohort	✓	✓	?	?	✓
Lo100	2012	US	2000–2007	28	⨯	Treatment cohort		✓		✓	✓
Salvati101	2012	Italy	1997–2007	84	⨯	Treatment cohort	✓	✓	?	?
Mathew102	2013	US	2008–2011	58	⨯	Treatment cohort				✓	✓
Miller103	2013	Germany	2000–2010	34	⨯	Treatment cohort	✓			✓	✓
Partl31	2013	Austria	1988–2009	87	⨯	Treatment cohort	✓	✓	?	?
Silk41	2013	US	2005–2012	70	⨯	Treatment cohort		✓	?	?	✓
Zukauskaite104	2013	Denmark	1995–2009	80	⨯	Treatment cohort	✓	✓	?	?	✓
Dyer105	2014	US	2000–2010	147	⨯	Treatment cohort		✓	✓		✓
Marcus106	2014	US	1998–2010	135	⨯	Treatment cohort	✓	✓	?	?	✓
Neal107	2014	US	2000–2009	129	⨯	Treatment cohort	✓	✓		✓	✓
Rades 108	2014	Germany	2000–2013	54	⨯	Treatment cohort			✓	✓
Vecchio109	2014	Italy	1994–2010	115	⨯	Disease cohort	✓	✓	?	?	✓
Christ110	2015	US	2005–2011	103	⨯	Treatment cohort	✓	✓	✓		✓
Frakes111	2015	US	2008–2012	28	⨯	Treatment cohort		✓	✓
Hauswald112	2015	Germany	1990–2011	84	⨯	Treatment cohort	✓	✓	✓		✓
Ivanov113	2015	Russia	2009–2013	95	⨯	Treatment cohort	✓	✓		✓
Ly114	2015	US	2009–2012	52	⨯	Treatment cohort	✓		✓
Ostheimer115	2015	Germany	1992–2011	100	⨯	Treatment cohort	✓	✓	?	?	✓
Gallaher116	2016	US	since 2006	19	⨯	Treatment cohort		✓		✓
Gupta29	2016	UK	NS	18	Yes	RCT		✓			✓
Patel117	2016	US	2007–2014 says (abstract 2005– 2013)	87	⨯	Treatment cohort			✓		✓
Rades118	2016	Germany	2000–2015	23	⨯	Treatment cohort		✓
Szyszka-Chare39	2016	Poland	1985–2012	110	⨯	Disease cohort	✓	✓	?	?	✓
Wolf119	2016	US	2012–2015	80	⨯	Treatment cohort	✓	✓		✓	✓
Acharya120	2017	US	2006–2016	72	⨯	Treatment cohort		✓		✓	✓
All121	2017	US	2008–2016	58	⨯	Treatment cohort			?	?
Feng122	2017	US	2007–2014	87	⨯	Treatment cohort	✓	✓	✓	✓	✓
Kaidar-Person123	2017	US	2007–2015	58	⨯	Treatment cohort		✓	✓		✓
Minniti124	2017	Italy	2008–2015	120	⨯	Treatment cohort	✓		✓		✓
Patel125	2017	US	2009–2013	54	⨯	Treatment cohort	✓		✓		✓
Pessina126	2017	Italy	2011–2015	53	⨯	Treatment cohort	✓		?	?
Sperduto127	2017	US	2006–2013	823/481	⨯	Disease cohort	✓	✓	?	?
Xu128	2017	US	2010–2014	65	⨯	Treatment cohort	✓	✓		✓	✓
Diao(A) 129	2018	US	2006–2015	72	⨯	Treatment cohort				✓	✓
Diao(B) 130	2018	US	2006–2015	91	⨯	Treatment cohort				✓	✓
Fang131	2018	US	2005–2011	235	⨯	Disease cohort	✓	✓	?	?	✓
Gabani132	2018	US	2011–2013	1104	⨯	Treatment cohort		✓	?	?	✓
Kano133	2018	US	1988–2012	422	⨯	Treatment cohort	✓	✓		✓	✓
Kotecha134	2018	US	1987–2014	366	⨯	Disease cohort	✓	✓	✓	✓	✓
Ladwa135	2018	Australia	2009–2016	142	⨯	Disease cohort	✓	✓	?	?
Matsunaga136	2018	Japan	1991–2015	177	⨯	Treatment cohort	✓	✓		✓	✓
Tio137	2018	Australia	2011–2014	355	⨯	Disease cohort	✓	✓	?	?	✓
Zubatkina138	2018	Russia	2009–2014	78	⨯	Treatment cohort	✓	✓		✓
Hauswald28	2019	Germany	2013–2017	7	Yes	RCT		✓
Hong30	2019	Australia	2009–2017	215	Yes	RCT	✓	✓	?	?	✓
Jardim139	2019	Australia	2015–2017	43	⨯	Treatment cohort	✓	✓		✓	✓
Mastorakos140	2019	US	2011–2015	198	⨯	Treatment cohort	✓	✓		✓	✓
Phillips42	2019	Canada	2000–2018	277	NS	Disease cohort		✓	?	?
Tjong141	2019	Canada	2008–2017	97	⨯	Treatment cohort	✓	✓	?	?
McHugh142	2020	Zealand New	2005–2017	110	⨯	Treatment cohort	✓	✓	?	?	✓
Pomeranz- Krumme143	2020	US	2010–2018	25	⨯	Treatment cohort	✓	✓	✓	✓	✓

Median survival within treatment groups and grouped by the first year of patient recruitment

First year of recruitment	Pre–1989			1990–2002			2003–2015			Not reported
First year of recruitment
	No. of studies	Median survival	IQR	No. of studies	Median survival	IQR	No. of studies	Median survival	IQR	No. of studies	Median survival	IQR
All patients	25	4.8	3.25–8.05	33	6.0	4.35–8.00	22	9.2	6.90–11.43	1	i3.0	NA
WBRT alone	17	3.6	2.49–4.0	7	2.5	2.3–4.0	6	4.2	2.75–4.80	3	4.3	3.40–6.40
SRS alone	2	i6.4, i7.7		4	7.3	5.78–7.88	2	i10.0, i11.9		0
WBRT and any of surgery, SRS, non-contemporary systemic therapy	43	7.4	4.00–9.20	23	7.3	5.50–10.00	4	8.0	5.73–10.50	2	i3.6, i4.3
SRS and any of surgery, WBRT, non-contemporary systemic therapy	17	8.3	5.90–9.65	29	7.9	5.85–10.04	18	9.0	6.90-13.00	0

Radiation therapy for melanoma brain metastases: a systematic review

Figures & Tables

Figure 1

Figure 2

Patient characteristics within treatment group for the 51 studies that reported baseline characteristics

Pooled outcome results for studies of radiation treatments

Studies of radiation treatment in patients with melanoma brain metastases

Median survival within treatment groups and grouped by the first year of patient recruitment

Paradigm

My account