Table 2. Open in new tab Selected...

Reference

CTV margin^*

% In-field

Definition of patterns of failure

Comments

Paulsson et al.⁴

5 mm
10 mm
15–20 mm

79%
77%
87%

In-field = failure within the 60 Gy isodose line

N = 161; PTV not specified;
No statistically significant difference in in-field failures between different CTV margins

Mendoza et al.⁵

5 mm (total treatment margin)

63%

In-field = recurrent tumor within or contiguous with the 5 mm margin
Marginal = recurrent tumor between 5 and 20 mm margin

N = 30; PTV = 0 mm
Three patients (11%) with marginal failure; only 1 patient (4%) may have dosimetrically benefited from a conventional 20 mm margin

McDonald et al.¹⁰⁴

Phase I: 5 mm (on T2-FLAIR)
Phase II: 5 mm (on GTV)

93%

In-field or central = 81–100% of recurrent tumor volume within the 60 Gy isodose line
Marginal = 20–80% of recurrent tumor volume within the 60 Gy isodose line
Distant = <20% of recurrent tumor volume within the 60 Gy isodose line

N = 62; PTV = 3–5 mm
Two patients (5%) had marginal failure, and 1 patient (2%) had distant failure

Brandes et al.¹⁰⁵

20–30 mm

72%

In-field = ≥ 80% of the tumor recurrence resided within the 95% prescription isodose surface
Marginal = 20–80% of the recurrent tumor was within the 95% prescription isodose surface

N = 95; PTV = up to 5 mm
Five patients (6.3%) had marginal failure, and 17 patients (21.5%) had distant failure

Gebhardt et al.²⁴

Phase I: 5 mm (on T2-FLAIR)
Phase II: 5 mm (on GTV)

81%

In-field = > 80% of the recurrent tumor was within the 95% isodose line
Marginal = > 20% but ≤ 80% of the recurrent tumor was within the 95% isodose line

N = 95; PTV = 5 mm
14 patients (15%) had only distant failures

Milano et al.¹⁰⁶

Phase I: 20 mm (on T2-FLAIR)
Phase II: 20–25 mm (on GTV)

80% (central)

Central = growth of original tumor or development of tumor(s) arising from surgical cavity
In-field = new tumor entirely within the 95% isodose line
Marginal = new lesion crosses the 95% isodose line
Distant = new lesion outside of the 95% isodose line

N = 54; PTV not specified;
33% developed new in-field recurrence, and 20% developed distant failures

Petrecca et al.¹⁰⁷

20 mm

85%

Resection margin = located at or in continuity with resection cavity
Distant = all other recurrent locations

N = 20; PTV = 5 mm
Two patients (10%) developed distant only recurrence

Sherriff et al.¹⁰⁸

15–20 mm

77% (central)

Central = progression of residual tumor enhancement, within 2 cm of the original mass
Distant = relapse > 4 cm from original tumor edge

N = 71; PTV = 5 mm
16 (22%) had distant failure

Kumar et al.¹⁶

RTOG approach:
Phase 1: 20 mm (on GTV + T2-FLAIR)
Phase 2: 25 mm (on GTV)
MDACC approach:
Phase 1: 20 mm (on GTV)
Phase 2: 5 mm (on GTV)

88% (central or in-field)
87% (central or in-field)

Central = >95% of recurrent tumor volume inside 95% isodose volume
In-field = >95% of recurrent tumor volume between 80% and 95% isodose volume
Marginal = >95% of recurrent tumor volume between 20% and 80% isodose volumes
Distant = >95% of recurrent tumor volume beyond 20% isodose volume

Total N = 50 (both arms); PTV = 5 mm
Two patients (12.5%) with marginal failure, no distant failure
One patient (6.25%) with marginal failure, and 1 patient (6.25%) with distant failure

Tu et al.¹⁰⁹

Phase 1: 20 mm
Phase 2: 5 mm

69%

In-field = >80% of recurrent tumor covered by 95% isodose line of boost plan (phase 2)
Marginal = 20–80% of recurrent tumor inside 95% isodose line of boost plan (phase 2)
Distant = <20% of recurrent tumor inside 95% isodose line of boost plan (phase 2)

N = 68; PTV = 5 mm
12 patients (17.7%) had distant failure; all recurrences were within 2 cm of original GTV, and 94.8% within 1 cm of original GTV

Zheng et al.¹¹⁰

Phase 1: 20 mm
Phase 2: 10 mm

84% (central or in-field)

Central = >95% of recurrent tumor volume within the 60 Gy isodose line
In-field = 80–95% of recurrent tumor volume within the 60 Gy isodose line
Marginal = 20–80% of recurrent tumor volume within the 60 Gy isodose line
Distant = <20% of recurrent tumor volume within the 60 Gy isodose line

N = 55; PTV = 3 mm
One patient (1.8%) had marginal recurrence and 11 patients (20.0%) had distant recurrences

Reference

CTV margin^*

% In-field

Definition of patterns of failure

Comments

Paulsson et al.⁴

5 mm
10 mm
15–20 mm

79%
77%
87%

In-field = failure within the 60 Gy isodose line

N = 161; PTV not specified;
No statistically significant difference in in-field failures between different CTV margins

Mendoza et al.⁵

5 mm (total treatment margin)

63%

In-field = recurrent tumor within or contiguous with the 5 mm margin
Marginal = recurrent tumor between 5 and 20 mm margin

N = 30; PTV = 0 mm
Three patients (11%) with marginal failure; only 1 patient (4%) may have dosimetrically benefited from a conventional 20 mm margin

McDonald et al.¹⁰⁴

Phase I: 5 mm (on T2-FLAIR)
Phase II: 5 mm (on GTV)

93%

N = 62; PTV = 3–5 mm
Two patients (5%) had marginal failure, and 1 patient (2%) had distant failure

Brandes et al.¹⁰⁵

20–30 mm

72%

In-field = ≥ 80% of the tumor recurrence resided within the 95% prescription isodose surface
Marginal = 20–80% of the recurrent tumor was within the 95% prescription isodose surface

N = 95; PTV = up to 5 mm
Five patients (6.3%) had marginal failure, and 17 patients (21.5%) had distant failure

Gebhardt et al.²⁴

Phase I: 5 mm (on T2-FLAIR)
Phase II: 5 mm (on GTV)

81%

In-field = > 80% of the recurrent tumor was within the 95% isodose line
Marginal = > 20% but ≤ 80% of the recurrent tumor was within the 95% isodose line

N = 95; PTV = 5 mm
14 patients (15%) had only distant failures

Milano et al.¹⁰⁶

Phase I: 20 mm (on T2-FLAIR)
Phase II: 20–25 mm (on GTV)

80% (central)

N = 54; PTV not specified;
33% developed new in-field recurrence, and 20% developed distant failures

Petrecca et al.¹⁰⁷

20 mm

85%

Resection margin = located at or in continuity with resection cavity
Distant = all other recurrent locations

N = 20; PTV = 5 mm
Two patients (10%) developed distant only recurrence

Sherriff et al.¹⁰⁸

15–20 mm

77% (central)

Central = progression of residual tumor enhancement, within 2 cm of the original mass
Distant = relapse > 4 cm from original tumor edge

N = 71; PTV = 5 mm
16 (22%) had distant failure

Kumar et al.¹⁶

RTOG approach:
Phase 1: 20 mm (on GTV + T2-FLAIR)
Phase 2: 25 mm (on GTV)
MDACC approach:
Phase 1: 20 mm (on GTV)
Phase 2: 5 mm (on GTV)

88% (central or in-field)
87% (central or in-field)

Total N = 50 (both arms); PTV = 5 mm
Two patients (12.5%) with marginal failure, no distant failure
One patient (6.25%) with marginal failure, and 1 patient (6.25%) with distant failure

Tu et al.¹⁰⁹

Phase 1: 20 mm
Phase 2: 5 mm

69%

N = 68; PTV = 5 mm
12 patients (17.7%) had distant failure; all recurrences were within 2 cm of original GTV, and 94.8% within 1 cm of original GTV

Zheng et al.¹¹⁰

Phase 1: 20 mm
Phase 2: 10 mm

84% (central or in-field)

N = 55; PTV = 3 mm
One patient (1.8%) had marginal recurrence and 11 patients (20.0%) had distant recurrences

Table 2.

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Selected Studies on Patterns of Progression Following Chemoradiotherapy for Glioblastoma

Reference	CTV margin^*	% In-field	Definition of patterns of failure	Comments
Paulsson et al.⁴	5 mm 10 mm 15–20 mm	79% 77% 87%	In-field = failure within the 60 Gy isodose line	N = 161; PTV not specified; No statistically significant difference in in-field failures between different CTV margins
Mendoza et al.⁵	5 mm (total treatment margin)	63%	In-field = recurrent tumor within or contiguous with the 5 mm margin Marginal = recurrent tumor between 5 and 20 mm margin	N = 30; PTV = 0 mm Three patients (11%) with marginal failure; only 1 patient (4%) may have dosimetrically benefited from a conventional 20 mm margin
McDonald et al.¹⁰⁴	Phase I: 5 mm (on T2-FLAIR) Phase II: 5 mm (on GTV)	93%	In-field or central = 81–100% of recurrent tumor volume within the 60 Gy isodose line Marginal = 20–80% of recurrent tumor volume within the 60 Gy isodose line Distant = <20% of recurrent tumor volume within the 60 Gy isodose line	N = 62; PTV = 3–5 mm Two patients (5%) had marginal failure, and 1 patient (2%) had distant failure
Brandes et al.¹⁰⁵	20–30 mm	72%	In-field = ≥ 80% of the tumor recurrence resided within the 95% prescription isodose surface Marginal = 20–80% of the recurrent tumor was within the 95% prescription isodose surface	N = 95; PTV = up to 5 mm Five patients (6.3%) had marginal failure, and 17 patients (21.5%) had distant failure
Gebhardt et al.²⁴	Phase I: 5 mm (on T2-FLAIR) Phase II: 5 mm (on GTV)	81%	In-field = > 80% of the recurrent tumor was within the 95% isodose line Marginal = > 20% but ≤ 80% of the recurrent tumor was within the 95% isodose line	N = 95; PTV = 5 mm 14 patients (15%) had only distant failures
Milano et al.¹⁰⁶	Phase I: 20 mm (on T2-FLAIR) Phase II: 20–25 mm (on GTV)	80% (central)	Central = growth of original tumor or development of tumor(s) arising from surgical cavity In-field = new tumor entirely within the 95% isodose line Marginal = new lesion crosses the 95% isodose line Distant = new lesion outside of the 95% isodose line	N = 54; PTV not specified; 33% developed new in-field recurrence, and 20% developed distant failures
Petrecca et al.¹⁰⁷	20 mm	85%	Resection margin = located at or in continuity with resection cavity Distant = all other recurrent locations	N = 20; PTV = 5 mm Two patients (10%) developed distant only recurrence
Sherriff et al.¹⁰⁸	15–20 mm	77% (central)	Central = progression of residual tumor enhancement, within 2 cm of the original mass Distant = relapse > 4 cm from original tumor edge	N = 71; PTV = 5 mm 16 (22%) had distant failure
Kumar et al.¹⁶	RTOG approach: Phase 1: 20 mm (on GTV + T2-FLAIR) Phase 2: 25 mm (on GTV) MDACC approach: Phase 1: 20 mm (on GTV) Phase 2: 5 mm (on GTV)	88% (central or in-field) 87% (central or in-field)	Central = >95% of recurrent tumor volume inside 95% isodose volume In-field = >95% of recurrent tumor volume between 80% and 95% isodose volume Marginal = >95% of recurrent tumor volume between 20% and 80% isodose volumes Distant = >95% of recurrent tumor volume beyond 20% isodose volume	Total N = 50 (both arms); PTV = 5 mm Two patients (12.5%) with marginal failure, no distant failure One patient (6.25%) with marginal failure, and 1 patient (6.25%) with distant failure
Tu et al.¹⁰⁹	Phase 1: 20 mm Phase 2: 5 mm	69%	In-field = >80% of recurrent tumor covered by 95% isodose line of boost plan (phase 2) Marginal = 20–80% of recurrent tumor inside 95% isodose line of boost plan (phase 2) Distant = <20% of recurrent tumor inside 95% isodose line of boost plan (phase 2)	N = 68; PTV = 5 mm 12 patients (17.7%) had distant failure; all recurrences were within 2 cm of original GTV, and 94.8% within 1 cm of original GTV
Zheng et al.¹¹⁰	Phase 1: 20 mm Phase 2: 10 mm	84% (central or in-field)	Central = >95% of recurrent tumor volume within the 60 Gy isodose line In-field = 80–95% of recurrent tumor volume within the 60 Gy isodose line Marginal = 20–80% of recurrent tumor volume within the 60 Gy isodose line Distant = <20% of recurrent tumor volume within the 60 Gy isodose line	N = 55; PTV = 3 mm One patient (1.8%) had marginal recurrence and 11 patients (20.0%) had distant recurrences

Reference	CTV margin^*	% In-field	Definition of patterns of failure	Comments
Paulsson et al.⁴	5 mm 10 mm 15–20 mm	79% 77% 87%	In-field = failure within the 60 Gy isodose line	N = 161; PTV not specified; No statistically significant difference in in-field failures between different CTV margins
Mendoza et al.⁵	5 mm (total treatment margin)	63%	In-field = recurrent tumor within or contiguous with the 5 mm margin Marginal = recurrent tumor between 5 and 20 mm margin	N = 30; PTV = 0 mm Three patients (11%) with marginal failure; only 1 patient (4%) may have dosimetrically benefited from a conventional 20 mm margin
McDonald et al.¹⁰⁴	Phase I: 5 mm (on T2-FLAIR) Phase II: 5 mm (on GTV)	93%	In-field or central = 81–100% of recurrent tumor volume within the 60 Gy isodose line Marginal = 20–80% of recurrent tumor volume within the 60 Gy isodose line Distant = <20% of recurrent tumor volume within the 60 Gy isodose line	N = 62; PTV = 3–5 mm Two patients (5%) had marginal failure, and 1 patient (2%) had distant failure
Brandes et al.¹⁰⁵	20–30 mm	72%	In-field = ≥ 80% of the tumor recurrence resided within the 95% prescription isodose surface Marginal = 20–80% of the recurrent tumor was within the 95% prescription isodose surface	N = 95; PTV = up to 5 mm Five patients (6.3%) had marginal failure, and 17 patients (21.5%) had distant failure
Gebhardt et al.²⁴	Phase I: 5 mm (on T2-FLAIR) Phase II: 5 mm (on GTV)	81%	In-field = > 80% of the recurrent tumor was within the 95% isodose line Marginal = > 20% but ≤ 80% of the recurrent tumor was within the 95% isodose line	N = 95; PTV = 5 mm 14 patients (15%) had only distant failures
Milano et al.¹⁰⁶	Phase I: 20 mm (on T2-FLAIR) Phase II: 20–25 mm (on GTV)	80% (central)	Central = growth of original tumor or development of tumor(s) arising from surgical cavity In-field = new tumor entirely within the 95% isodose line Marginal = new lesion crosses the 95% isodose line Distant = new lesion outside of the 95% isodose line	N = 54; PTV not specified; 33% developed new in-field recurrence, and 20% developed distant failures
Petrecca et al.¹⁰⁷	20 mm	85%	Resection margin = located at or in continuity with resection cavity Distant = all other recurrent locations	N = 20; PTV = 5 mm Two patients (10%) developed distant only recurrence
Sherriff et al.¹⁰⁸	15–20 mm	77% (central)	Central = progression of residual tumor enhancement, within 2 cm of the original mass Distant = relapse > 4 cm from original tumor edge	N = 71; PTV = 5 mm 16 (22%) had distant failure
Kumar et al.¹⁶	RTOG approach: Phase 1: 20 mm (on GTV + T2-FLAIR) Phase 2: 25 mm (on GTV) MDACC approach: Phase 1: 20 mm (on GTV) Phase 2: 5 mm (on GTV)	88% (central or in-field) 87% (central or in-field)	Central = >95% of recurrent tumor volume inside 95% isodose volume In-field = >95% of recurrent tumor volume between 80% and 95% isodose volume Marginal = >95% of recurrent tumor volume between 20% and 80% isodose volumes Distant = >95% of recurrent tumor volume beyond 20% isodose volume	Total N = 50 (both arms); PTV = 5 mm Two patients (12.5%) with marginal failure, no distant failure One patient (6.25%) with marginal failure, and 1 patient (6.25%) with distant failure
Tu et al.¹⁰⁹	Phase 1: 20 mm Phase 2: 5 mm	69%	In-field = >80% of recurrent tumor covered by 95% isodose line of boost plan (phase 2) Marginal = 20–80% of recurrent tumor inside 95% isodose line of boost plan (phase 2) Distant = <20% of recurrent tumor inside 95% isodose line of boost plan (phase 2)	N = 68; PTV = 5 mm 12 patients (17.7%) had distant failure; all recurrences were within 2 cm of original GTV, and 94.8% within 1 cm of original GTV
Zheng et al.¹¹⁰	Phase 1: 20 mm Phase 2: 10 mm	84% (central or in-field)	Central = >95% of recurrent tumor volume within the 60 Gy isodose line In-field = 80–95% of recurrent tumor volume within the 60 Gy isodose line Marginal = 20–80% of recurrent tumor volume within the 60 Gy isodose line Distant = <20% of recurrent tumor volume within the 60 Gy isodose line	N = 55; PTV = 3 mm One patient (1.8%) had marginal recurrence and 11 patients (20.0%) had distant recurrences

^*On GTV unless otherwise specified.

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