Table 1.
Treatment for LM Diagnosis and Outcome
| MRI Subtype | All | Type I | Type II | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| All Patients | A | B | C | D | all I | A | B | C | D | all | |
| n = 254 | n = 88 | n = 19 | n = 39 | n = 43 | n = 189 | n = 29 | n = 13 | n = 16 | n = 7 | n = 65 | |
| 100% | 35% | 7% | 15% | 17% | 74% | 11% | 5% | 6% | 3% | 26% | |
| Systemic treatment | |||||||||||
| Any: n (%) | |||||||||||
| Yes | 104 (41) | 38 (43) | 6 (32) | 18 (46) | 14 (33) | 76 (40) | 12 (41) | 6 (46) | 9 (56) | 1 (14) | 28 (43) |
| No | 145 (57) | 46 (52) | 13 (69) | 21 (54) | 29 (67) | 109 (58) | 17 (59) | 6 (46) | 7 (44) | 6 (86) | 36 (55) |
| unknown | 5 (2) | 4 (5) | 0 | 0 | 0 | 4 (2) | 0 | 1 (8) | 0 | 0 | 1 (2) |
| Intrathecal treatment | |||||||||||
| Intrathecal therapy: n (%) | |||||||||||
| Yes | 117 (46) | 44 (50) | 4 (21) | 23 (59) | 21 (49) | 92 (49) | 13 (45) | 3 (23) | 6 (37.5) | 3 (43) | 25 (38) |
| No | 137 (54) | 44 (50) | 15 (79) | 16 (41) | 22 (51) | 97 (51) | 16 (55) | 10 (77) | 10 (62.5) | 4 (57) | 40 (62) |
| Agent: n (%) | |||||||||||
| Liposomal cytarabine | 71 (60) | 25 (56) | 2 (50) | 17 (71) | 12 (57) | 56 (30) | 8 (62) | 2 (67) | 3 (50) | 2 (67) | 15 (23) |
| Cytarabine | 12 (10) | 8 (18) | 0 | 1 (5) | 1 (5) | 10 (5) | 1 (8) | 1 (33) | 0 | 0 | 2 (3) |
| Methotrexate | 25 (21) | 10 (22) | 1 (25) | 3 (12.5) | 7 (33) | 21 (11) | 2 (15) | 0 | 1 (17) | 1 (33) | 4 (6) |
| Thiotepa | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Trastuzumab | 6 (5) | 1 (2) | 0 | 3 (12.5) | 0 | 4 (2) | 0 | 0 | 2 (33) | 0 | 2 (3) |
| Liposomal cytarabine + MTX | 1 (1) | 0 | 1 (25) | 0 | 0 | 1 (<0.5) | 0 | 0 | 0 | 0 | 0 |
| Cytarabine + MTX | 4 (3) | 1 (2) | 0 | 0 | 1 (5) | 2 (1) | 2 (15) | 0 | 0 | 0 | 2 (3) |
| Route of administration: n (%) | |||||||||||
| Lumbar only | 92 (79) | 36 (82) | 4 (100) | 17 (74) | 17 (81) | 74 (39) | 8 (62) | 2 (67) | 5 (83) | 3 (100) | 18 (28) |
| Ventricular only | 14 (12) | 5 (11) | 0 | 2 (9) | 4 (19) | 11 (6) | 2 (16) | 1 (33) | 0 | 0 | 3 (5) |
| Both | 10 (9) | 3 (7) | 0 | 4 (17) | 0 | 7 (4) | 2 (15) | 0 | 1 (17) | 0 | 3 (5) |
| Unknown | 1 (1) | 0 | 0 | 0 | 0 | 0 | 1 (8) | 0 | 0 | 0 | 1 (2) |
| Radiotherapy | |||||||||||
| Radiotherapy for LM: n (%) | |||||||||||
| Local radiotherapy, including radiosurgery | 12 (5) | 3 (3) | 1 (5) | 3 (8) | 0 | 7 (4) | 3 (10) | 1 (8) | 1 (6) | 0 | 5 (8) |
| Whole brain radiotherapy | 91 (36) | 27 (31) | 5 (26) | 20 (51) | 14 (33) | 66 (35) | 11 (38) | 5 (38) | 6 (37.5) | 3 (43) | 25 (38) |
| Whole spine RT | 1 (0.5) | 1 (1) | 0 | 0 | 9 | 1 (<0.5) | 0 | 0 | 0 | 0 | 0 |
| None | 149 (59) | 56 (64) | 13 (68) | 16 (41) | 29 (67) | 114 (60) | 15 (52) | 7 (54) | 9 (56) | 4 (57) | 35 (54) |
| Unknown | 1 (0.5) | 1 (1) | 0 | 0 | 0 | 1 (<0.5) | 0 | 0 | 0 | 0 | 0 |
| Radiotherapy for concomitant progressive brain metastases: n (%) | |||||||||||
| Local radiotherapy, including radiosurgery | 8 (3) | 0 | 1 (5) | 1 (3) | 2 (5) | 4 (2) | 2 (7) | 2 (15) | 0 | 0 | 4 (6) |
| Whole brain radiotherapy | 47 (18.5) | 10 (11) | 4 (1) | 14 (36) | 3 (7) | 31 (16) | 7 (24) | 4 (31) | 4 (25) | 1 (14) | 16 (25) |
| None | 183 (72) | 72 (82) | 13 (68) | 23 (59) | 34 (79) | 142 (75) | 19 (66) | 5 (38) | 12 (75) | 5 (71) | 41 (63) |
| Unknown | 16 (6.5) | 6 (7) | 1 (5) | 1 (3) | 4 (9) | 12 (6) | 1 (3) | 2 (15) | 0 | 1 (14) | 4 (6) |
| Radiotherapy for LM or BM after LM diagnosis: n (%) | |||||||||||
| Local radiotherapy, including radiosurgery | 14 (5.5) | 3 (3) | 1 (5) | 3 (8) | 1 (2) | 8 (4) | 3 (10) | 2 (15) | 1 (6) | 0 | 6 (9) |
| Whole brain radiotherapy | 91 (36) | 26 (30) | 5 (26) | 21 (54) | 13 (30) | 65 (34) | 11 (38) | 5 (38) | 6 (37.5) | 4 (57) | 6 (40) |
| Whole spine RT | 1 (0.5) | 1 (1) | 0 | 0 | 0 | 1 (<0.5) | 0 | 0 | 0 | 0 | 0 |
| WBRT + SRT | 3 (1) | 0 | 0 | 0 | 1 (2) | 1 (<0.5) | 1 (3) | 1 (8) | 0 | 0 | 2 (3) |
| None | 129 (51) | 52 (59) | 12 (63) | 14 (36) | 24 (56) | 102 (54) | 13 (45) | 3 (23) | 9 (56) | 2 (29) | 27 (42) |
| Unknown | 16 (6) | 6 (7) | 1 (5) | 1 (3) | 4 (9) | 12 (6) | 1 (3) | 2 (15) | 0 | 1 (14) | 4 (6) |
| Combination of treatment | |||||||||||
| Modalities: n (%) | |||||||||||
| Systemic alone | 23 (9) | 8 (9) | 4 (21) | 2 (5) | 4 (9) | 18 (9) | 1 (3) | 3 (23) | 1 (6) | 0 | 5 (8) |
| Intrathecal alone | 41 (16) | 13 (15) | 2 (10.5) | 7 (18) | 12 (28) | 34 (18) | 5 (17) | 1 (8) | 0 | 1 (14) | 7 (11) |
| Radiotherapy alone | 42 (16) | 11 (12.5) | 4 (21) | 5 (26) | 9 (21) | 29 (15) | 5 (17) | 3 (23) | 3 (19) | 2 (29) | 13 (20) |
| Systemic + intrathecal | 38 (15) | 16 (18) | 1 (5) | 4 (10) | 6 (14) | 27 (14) | 5 (17) | 0 | 5 (31) | 1 (14) | 11 (17) |
| Systemic + RT | 29 (11) | 9 (10) | 1 (5) | 6 (15) | 2 (5) | 18 (9) | 6 (21) | 2 (15) | 3 (19) | 0 | 11 (17) |
| Intrathecal + RT | 19 (7) | 6 (7) | 1 (5) | 6 (15) | 1 (2) | 14 (7) | 3 (10) | 0 | 1 (6) | 1 (14) | 5 (8) |
| Systemic + intrathecal + RT | 14 (5.5) | 5 (6) | 0 | 6 (15) | 2 (5) | 13 (7) | 0 | 1 (8) | 0 | 0 | 1 (1.5) |
| No treatment | 43 (17) | 16 (18) | 6 (31.5) | 3 (8) | 7 (18) | 32 (17) | 4 (14) | 2 (15) | 3 (19) | 2 (29) | 11 (17) |
| Unknown | 5 (2) | 4 (4) | 0 | 0 | 0 | 4 (2) | 0 | 1 (8) | 0 | 0 | 1 (1.5) |
| Outcome from diagnosis of LM | |||||||||||
| Type of any first progression | |||||||||||
| LM | 134 (53) | 61 (69) | 9 (47) | 23 (74) | 21 (49) | 114 (60) | 6 (21) | 6 (46) | 5 (31) | 3 (43) | 20 (31) |
| BM | 6 (2) | 1 (1) | 0 | 0 | 0 | 1 (<0.5) | 1 (3) | 1 (7) | 2 (12.5) | 1 (14) | 5 (8) |
| Extra-CNS | 24 (9) | 5 (6) | 2 (10.5) | 2 (5) | 6 (14) | 15 (8) | 5 (17) | 1 (7) | 2 (12.5) | 1 (14) | 9 (14) |
| LM + BM | 13 (5) | 1 (1) | 2 (10.5) | 3 (8) | 2 (4) | 8 (4) | 4 (14) | 0 | 1 (6) | 0 | 5 (8) |
| LM + extra-CNS | 17 (7) | 6 | 0 | 5 (13) | 2 (4) | 13 (7) | 2 (7) | 2 (15) | 0 | 0 | 4 (6) |
| BM + extra-CNS | 1 (<0.5) | 0 | 0 | 0 | 1 (<0.5) | 1 (<0.5) | 0 | 0 | 0 | 0 | 0 |
| LM + BM + extra-CNS | 2 (<0.5) | 0 | 1 (0.5) | 0 | 0 | 1 (<0.5) | 0 | 0 | 1 (6) | 0 | 1 (1) |
| None | 17 (7) | 3 (3) | 3 (16) | 2 (5) | 4 (9) | 12 (6) | 4 (14) | 0 | 1 (6) | 0 | 5 (8) |
| Unknown | 40 (16) | 11 (12) | 2 (10.5) | 4 (10) | 7 (16) | 24 (13) | 7 (24) | 3 (23) | 4 (25) | 2 (29) | 16 (25) |
| LM progression: n (%) | |||||||||||
| No | 30 (12) | 5 (6) | 4 (21) | 2 (5) | 10 (23) | 21 (11) | 6 (21) | 0 | 2 (12.5) | 1 (14) | 9 (14) |
| Yes | 186 (73) | 74 (84) | 13 (68) | 32 (82) | 27 (63) | 146 (77) | 16 (55) | 9 (69) | 11 (69) | 4 (57) | 40 (62) |
| Unknown | 38 (15) | 9 (10) | 2 (11) | 5 (13) | 6 (14) | 22 (12) | 7 (24) | 4 (31) | 3 (19) | 2 (29) | 16 (25) |
| LM PFS, in months: median (IQR) | 1.75 (0.7–3.7) (n = 156) | 1.7 (0.6–3.7) (n = 60) | 1.2 (0.2–1.6) (n = 12) | 2.0 (0.7–3.0) (n = 29) | 1.0 (0.5–2.3) (n = 23) | 1.5 (0.6–3.0) (n = 124) | 5.4 (2.4–9.5) (n = 14) | 2.8 (2.6–5.1) (n = 5) | 1.4 (1.0–4.2) (n = 10) | 3.2 (1.8–5.5) (n = 3) | 3.0 (1.5–7.8) (n = 32) |
| BM progression: n (%) | |||||||||||
| No | 96 (38) | 33 (37.5) | 11 (58) | 16 (41) | 17 (40) | 77 (41) | 9 (31) | 3 (23) | 4 (25) | 3 (43) | 19 (29) |
| Yes | 32 (13) | 3 (3) | 3 (16) | 7 (18) | 4 (9) | 17 9) | 9 (8) | 1 (8) | 4 (25) | 1 (14) | 15 (23) |
| Unknown | 107 (42) | 52 (59) | 5 (26) | 16 (41) | 2 (51) | 75 (40) | 12 (41) | 9 (69) | 8 (50) | 3 (43) | 32 (49) |
| Median BM PFS, in months: median (IQR) | 3.4 (1.8–8.5) (n = 26) | 2.1 (1.3–5.0) (n = 3) | 3.7 (3.7-3.7) (n = 1) | 10.5 (4–13.7) (n = 6) | 4.0 (2.7–6.1) (n = 3) | 4.0 (2.1–8.5) (n = 13) | 5.5 (1.9–11.7) (n = 8) | 2.8 (2.8-2.8) (n = 1) | 0.9 (0.7–1.2) (n = 3) | 3.1 (3.1-3.1) (n = 1) | 2.8 (1.7–7.4) (n = 13) |
| Extra CNS progression: n (%) | |||||||||||
| No | 77 (30) | 24 (27) | 10 (53) | 12 (31) | 11 (26) | 57 (30) | 9 (31) | 4 (31) | 6 (37.5) | 3 (43) | 22 (34) |
| Yes | 56 (22) | 17 (19) | 5 (26) | 8 (20) | 11 (26) | 41 (22) | 9 (31) | 3 (23) | 2 (12.5) | 1 (14) | 15 (23) |
| Unknown | 119 (47) | 47 (53) | 4 (21) | 19 (49) | 21 (49) | 91 (48) | 11 (38) | 6 (46) | 8 (50) | 3 (43) | 28 (43) |
| Median extra-CNS PFS, in months: median (IQR) | 3.3 (2.2–5.0) (n = 48) | 2.6 (1.8–3.6) (n = 13) | 3.3 (2.4–3.8) (n = 4) | 3.1 (2.7–3.7) (n = 8) | 2.5 (1.7–4.0) (n = 10) | 2.8 (1.9–3.8) (n = 35) | 8.0 (5.6–11.0) (n = 8) | 3.9 (3.3–4.5) (n = 2) | 2.4 (1.8–3.0) (n = 2) | 1.6 (1.6-1.6) (n = 1) | 5.1 (3.8–9.7) (n = 13) |
| Overall progression: n (%) | |||||||||||
| No | 12 (5) | 3 (3) | 2 (11) | 1 (3) | 4 (9) | 10 (5) | 1 (3) | 0 | 1 (6) | 0 | 2 (3) |
| Yes | 206 (81) | 76 (86) | 16 (84) | 33 (85) | 34 (79) | 159 (84) | 20 (69) | 10 (77) | 12 (75) | 5 (71) | 47 (72) |
| Unknown | 36 (14) | 9 (10) | 1 (5) | 5 (13) | 5 (12) | 20 (11) | 8 (28) | 3 (23) | 3 (19) | 2 (29) | 16 (25) |
| Median overall PFS, in months: median (IQR) | 1.7 (0.7–3.5) (n = 182) | 1.5 (0.5–3.1) (n = 62) | 1.4 (0.5–2.2) (n = 15) | 1.95 (0.8–3.3) (n = 34) | 1.4 (0.7–2.3) (n = 30) | 1.5 (0.6–2.8) (n = 141) | 4.8 (1.7–8) (n = 20) | 2.7 (2.6–5.1) (n = 6) | 1.22 (0.8–2.6) (n = 11) | 2.3 (1.3–3.1) (n = 4) | 2.6 (1.3–5.9) (n = 41) |
| Death: n (%) | |||||||||||
| Alive | 8 (3) | 2 (2) | 1 (5) | 0 | 1 (2) | 4 (2) | 2 (7) | 0 | 1 (6) | 1 (14) | 4 (6) |
| Dead | 240 (95) | 84 (95) | 18 (95) | 39 (100) | 40 (93) | 181 (96) | 25 (86) | 13 (100) | 15 (94) | 6 (86) | 59 (91) |
| Lost of follow-up | 6 (2) | 2 (2) | 0 | 0 | 2 (5) | 4 (2) | 2 (7) | 0 | 0 | 0 | 2 (3) |
| Overall survival in months: median (IQR) | 2.8 (1.0–6.0) (n = 254) | 2.2 (0.8–4.7) (n = 88) | 2.2 (0.8–4.9) (n = 19) | 3.3 (1.1–7) (n = 39) | 2 (0.6–3.8) (n = 43) | 2.3 (0.82–4.9) (n = 189) | 6.5 (1.9-15) (n = 29) | 3.4 (2.1–4.7) (n = 13) | 2.1 (1.5–6.5) (n = 16) | 3.5 (2.7–5.1) (n = 7) | 3.5 (1.6–9.4) (n = 65) |
| Overall survival breast cancer patients: median (IQR) | 3.4 (1.3–7.5) (n = 104) | 2.2 (0.8–5.5) (n = 29) | 3.1 (2.1–6.4) (n = 7) | 5.8 (3.5–9.8) (n = 12) | 2.1 (1.1–3.9) (n = 19) | 22.4 (1.0–6.6) (n = 68) | 19.7 (8.3–28.6) (n = 10) | 2.8 (1.8–4.0) (n = 7) | 1.5 (1.5–1.6) (n = 2) | 3.5 (3.3–4.3) (n = 3) | 4.5 (2.5–10.5) (n = 36) |
| Overall survival lung cancer patients: median (IQR) | 2.2 (0.9–4.6) (n = 65) | 2.9 (0.9–4.7) (n = 32) | 2 (0.4–2.2) (n = 5) | 1.1 (1.1–3.3) (n = 5) | 1.9 (0.4–4.7) (n = 11) | 2 (0.8–4.4) (n = 55) | 8.4 (5–11.7) (n = 2) | 4.3 (3.9–4.9) (n = 4) | 9.2 (6.5–10.2) (n = 6) | n.a. | 2.9 (1.7–4.5) (n = 10) |
| Overall survival melanoma patients: median (IQR) | 1.7 (0.9–5.2) (n = 51) | 3.1 (0.8–3.9) (n = 15) | 0.6 (0.6–7.2) (n = 6) | 3.4 (1.3–10.5) (n = 11) | 1.5 (0.9–2.2) (n = 6) | 1.5 (0.8–4.3) (n = 39) | 2.9 (1.9–5.7) (n = 6) | 13.3 (7.3–19.2) (n = 2) | 1.5 (1.4–1.6) (n = 3) | 29.7 (29.7-29.7) (n = 1) | 2.2 (1.5–8.1) (n = 12) |
| Overall survival other primaries: median (IQR) | 2.0 (1.0–5.3) (n = 34) | 1.0 (0.5–4.6) (n = 12) | 2.7 (2.2–3.3) (n = 2) | 3.0 (1.4–9.2) (n = 6) | 2.3 (0.7–3.2) (n = 7) | 2.3 (0.6–4.1) (n = 27) | 5.7 (3.6–8.3) (n = 3) | n.a. | 1.3 (1.3-1.3) (n = 1) | 29 (29-29) (n = 1) | 1.5 (1.2–8.3) (n = 7) |
| Cause of death: n (%) | |||||||||||
| Neurological | 131 (55) | 51 (58) | 10 (53) | 23 (59) | 22 (55) | 106 (56) | 8 (28) | 6 (46) | 7 (44) | 4 (57) | 25 (38) |
| Extra-CNS | 17 (7) | 4 (5) | 3 (16) | 1 (3) | 2 (5) | 10 (5) | 5 (17) | 1 (8) | 1 (6) | 0 | 7 (11) |
| CNS and extra-CNS | 2 (1) | 0 | 0 | 1 (3) | 1 (2) | 2 (1) | 0 | 0 | 0 | 0 | 0 |
| Complication of treatment | 4 (2) | 2 (2) | 1 (5) | 0 | 0 | 3 (2) | 1 (3) | 0 | 0 | 0 | 1 (2) |
| Other | 10 (4) | 5 (6) | 0 | 1 (3) | 2 (5) | 8 (4) | 1 (3) | 1 (8) | 0 | 0 | 2 (3) |
| Unknown | 75 (31) | 26 (30) | 5 (26) | 13 (33) | 16 (37) | 60 (32) | 14 (48) | 5 (38) | 8 (50) | 3 (43) | 30 (46) |
Abbreviations: BM, brain metastases; CNS, central nervous system; CSF, cerebrospinal fluid; IQR, interquartile ranges; LM, leptomeningeal metastases; MTX, methotrexate; n, number; n.a., not applicable; PFS, progression free survival; RT, radiotherapy; SRT, stereotactic radiotherapy; WBRT, whole brain radiotherapy.