The Analysis of Trends in Survival for Patients with Melanoma Brain Metastases with Introduction of Novel Therapeutic Options before the Era of Combined Immunotherapy—Multicenter Italian–Polish Report
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient Cohort and Inclusion Criteria
2.2. Collected Covariates
2.3. Analysis Plan and Handling of Missing Data
2.4. Statistical Methods
2.5. Ethical Statement
3. Results
3.1. Patient Characteristics
3.2. Prognostic Factors at MBM Diagnosis
3.3. Treatment
4. Discussion
- Patients diagnosed with MBM after 2017 had a better prognosis in our cohort, with a significantly improved median of overall survival after 2017. The biggest change was observed in the poorest prognostic mol-GPA groups, in which survival improved significantly after 2017.
- The outcome of patients with MBM improved when local therapy (neurosurgery ± SRS) was combined with modern systemic therapy. The implementation of systemic therapy and surgery was associated with improved OS regardless of the timing to MBM treatment start (i.e., before or after 30 days from MBM diagnosis).
- The introduction of local therapy for MBM treatment significantly improved survival regardless of the year of diagnosis (treated after or before 2017), with a median survival of more than 12 months.
- In our prognostic model, the presence of MBM symptoms without steroid use did not have prognostic significance.
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Prognostic Part | Treatment Part | ||||
---|---|---|---|---|---|
Data Analyzed | Variable | Overall | Missing | Overall | Missing |
number of pts (%) | % | number of pts (%) | % | ||
487 | 402 | ||||
Sex | female | 204 (41.9) | 0 | 169 (42.0) | 0 |
male | 283 (58.1) | 233 (58.0) | |||
CNS involvement type | both | 14 (2.9) | 0 | 9 (2.2) | 0 |
brain | 468 (96.1) | 391 (97.3) | |||
meninges | 5 (1.0) | 2 (0.5) | |||
BRAF mutation status | v600 | 316 (64.9) | 0 | 255 (63.4) | 0 |
wt | 171 (35.1) | 147 (36.6) | |||
Presence of lung metastases | no | 217 (44.6) | 0 | 175 (43.5) | 0 |
yes | 270 (55.4) | 227 (56.5) | |||
Presence of visceral metastases | no | 270 (55.4) | 0 | 231 (57.5) | 0 |
yes | 217 (44.6) | 171 (42.5) | |||
No. of MBM | 1 | 131 (26.9) | 0 | 95 (23.6) | 0 |
2 | 58 (11.9) | 50 (12.4) | |||
3 | 44 (9.0) | 39 (9.7) | |||
4 | 15 (3.1) | 11 (2.7) | |||
5+ | 239 (49.1) | 207 (51.5) | |||
Diameter of MBM (mm) (median (IQR)) | 16.00 [9.00, 27.00] | 28.1 | 16.00 [10.00, 27.00] | 25.9 | |
Karnofsky performance status | <70 | 119 (24.4) | 0 | 52 (12.9) | 0 |
100 | 53 (10.9) | 43 (10.7) | |||
70 | 84 (17.2) | 83 (20.6) | |||
80 | 98 (20.1) | 95 (23.6) | |||
90 | 133 (27.3) | 129 (32.1) | |||
Presence of CNS symptoms | no | 177 (40.7) | 10.7 | 163 (42.7) | 5 |
yes | 258 (59.3) | 219 (57.3) | |||
Use of GCS | no | 110 (22.6) | 0 | 106 (26.4) | 0 |
unknown | 102 (20.9) | 63 (15.7) | |||
yes | 275 (56.5) | 233 (58.0) | |||
Use of previous treatment | 0 | 306 (62.8) | 0 | 252 (62.7) | 0 |
1 | 128 (26.3) | 102 (25.4) | |||
2+ | 53 (10.9) | 48 (11.9) | |||
Extracranial involvement | no | 237 (48.7) | 0 | 183 (45.5) | 0 |
yes | 250 (51.3) | 219 (54.5) | |||
Age (median (IQR)) | 56.00 [44.00, 65.00] | 0 | 56.00 [44.00, 65.00] | 0 | |
Previous chemotherapy | no | 451 (92.6) | 0 | 368 (91.5) | 0 |
yes | 36 (7.4) | 34 (8.5) | |||
Previous BRAF/MEK inhibitors | no | 451 (92.6) | 0 | 372 (92.5) | 0 |
yes | 36 (7.4) | 30 (7.5) | |||
Previous BRAF inhibitors | no | 453 (93.0) | 0 | 372 (92.5) | 0 |
yes | 34 (7.0) | 30 (7.5) | |||
Previous ipilimumab | no | 460 (94.5) | 0 | 377 (93.8) | 0 |
yes | 27 (5.5) | 25 (6.2) | |||
Previous anti-pd1 antibodies | no | 460 (94.5) | 0 | 377 (93.8) | 0 |
yes | 27 (5.5) | 25 (6.2) | |||
No. of pts with MBM diagnosis by year | <2017 | 235 (48.3) | 0 | 207 (51.5) | 0 |
≥2017 | 252 (51.7) | 195 (48.5) |
Analyzed Variables | Full Model | Reduced Model | ||||||
---|---|---|---|---|---|---|---|---|
Term | HR | Lower 95 | Upper 95 | p-Value | HR | Lower 95 | Upper 95 | p-Value |
Sex male | 1.16 | 0.95 | 1.42 | 0.139 | ||||
Age (per 1 year change) | 1.01 | 1 | 1.02 | 0.0056 | 1.01 | 1 | 1.02 | 0.0048 |
BRAF status (WT vs. mutated) | 1.31 | 1.05 | 1.64 | 0.0159 | 1.33 | 1.07 | 1.66 | 0.0114 |
Lung metastases (yes vs. no) | 1.24 | 1.01 | 1.54 | 0.0446 | 1.25 | 1.01 | 1.54 | 0.0375 |
Visceral metastases (yes vs. no) | 1.3 | 1.05 | 1.61 | 0.0168 | 1.27 | 1.03 | 1.57 | 0.0239 |
Other extracranial metastases (yes vs. no) | 0.98 | 0.8 | 1.21 | 0.8665 | ||||
No. of CNS metastases = 1 | Reference | Reference | ||||||
No. of CNS metastases = 2–4 | 1.65 | 1.23 | 2.21 | 0.0009 | 1.6 | 1.19 | 2.13 | 0.0017 |
No. of CNS metastases >5 | 2.1 | 1.61 | 2.73 | <0.0001 | 2.08 | 1.61 | 2.7 | <0.0001 |
Diameter of biggest CNS meta (per 1mm change) | 1 | 0.99 | 1.01 | 0.3625 | ||||
Year of MBM diagnosis (per 1 year change since 2014) | 0.91 | 0.85 | 0.97 | 0.0038 | 0.91 | 0.86 | 0.97 | 0.0045 |
Karnofsky performance status score (per 10 pts change) | 0.9 | 0.83 | 0.98 | 0.011 | 0.9 | 0.83 | 0.97 | 0.009 |
No CNS symptoms, no GCS use | Reference | Reference | ||||||
No CNS symptoms, GCS due to other causes | 1.42 | 1 | 2.03 | 0.0525 | 1.42 | 0.99 | 2.02 | 0.0549 |
CNS symptoms, no GKS use | 1.16 | 0.8 | 1.69 | 0.4309 | 1.22 | 0.85 | 1.76 | 0.2832 |
CNS symptoms requiring GCS | 1.63 | 1.23 | 2.16 | 0.0007 | 1.69 | 1.29 | 2.21 | 0.0001 |
No previous systemic treatment | Reference | Reference | ||||||
1 line of previous systemic treatment | 1.65 | 1.31 | 2.08 | <0.0001 | 1.65 | 1.31 | 2.09 | <0.0001 |
>1 line of previous systemic treatment | 1.62 | 1.16 | 2.27 | 0.0051 | 1.57 | 1.14 | 2.16 | 0.0062 |
Term | HR | Lower_95 | Upper_95 | p-Value |
---|---|---|---|---|
molGPA 3.5–4 | Reference | |||
molGPA 2.5–3 | 1.88 | 1.31 | 2.7 | 0.0007 |
molGPA 1.5–2 | 2.83 | 1.98 | 4.03 | <0.0001 |
molGPA 0–1 | 4.84 | 3.26 | 7.17 | <0.0001 |
Factor | HR | p-Value | Lower 95 | Upper 95 |
---|---|---|---|---|
for no symptoms and no GCs as a reference group | ||||
pts with no symptoms and on GCS | 1.81 | 0.0006 | 1.29 | 2.53 |
pts with symptoms without GCS | 1.26 | 0.1767 | 0.90 | 1.78 |
pts with symptoms on GCS | 1.98 | 0.0000 | 1.56 | 2.53 |
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Placzke, J.; Teterycz, P.; Quaglino, P.; Cybulska-Stopa, B.; Tucci, M.; Rubatto, M.; Skora, T.; Interno, V.; Rosinska, M.; Borkowska, A.; et al. The Analysis of Trends in Survival for Patients with Melanoma Brain Metastases with Introduction of Novel Therapeutic Options before the Era of Combined Immunotherapy—Multicenter Italian–Polish Report. Cancers 2022, 14, 5763. https://doi.org/10.3390/cancers14235763
Placzke J, Teterycz P, Quaglino P, Cybulska-Stopa B, Tucci M, Rubatto M, Skora T, Interno V, Rosinska M, Borkowska A, et al. The Analysis of Trends in Survival for Patients with Melanoma Brain Metastases with Introduction of Novel Therapeutic Options before the Era of Combined Immunotherapy—Multicenter Italian–Polish Report. Cancers. 2022; 14(23):5763. https://doi.org/10.3390/cancers14235763
Chicago/Turabian StylePlaczke, Joanna, Paweł Teterycz, Pietro Quaglino, Bozena Cybulska-Stopa, Marco Tucci, Marco Rubatto, Tomasz Skora, Valeria Interno, Magdalena Rosinska, Aneta Borkowska, and et al. 2022. "The Analysis of Trends in Survival for Patients with Melanoma Brain Metastases with Introduction of Novel Therapeutic Options before the Era of Combined Immunotherapy—Multicenter Italian–Polish Report" Cancers 14, no. 23: 5763. https://doi.org/10.3390/cancers14235763