Factors Influencing the Adjuvant Therapy Decision: Results of a Real-World Multicenter Data Analysis of 904 Melanoma Patients
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient Selection
2.2. Statistical Analysis
3. Results
3.1. Decision on Adjuvant Treatment
3.2. Treatment Choice between Targeted and Immunotherapy in BRAF-Mutant Patients
4. Discussion
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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Characteristics | Total Cohort | Adjuvant Treatment Cohort | No Adjuvant Treatment Cohort | p-Value e | |||
---|---|---|---|---|---|---|---|
n | % | n | % (95% CI) | n | % (95% CI) | - | |
- | 904 | 100.0 | 695 | 76.9 (74.3–79.6) | 209 | 23.1 (20.4–25.7) | - |
Median age (range) | 64.9 (19.2–98.1) | - | 61.8 (19.2–89.9) | (60–62) | 76.3 (27.7–98.1) | (70–74) | <0.001 |
Gender | - | - | - | - | - | - | 0.92 |
Female | 378 | 41.8 | 290 | 76.7 (72.2–81.1) | 88 | 23.3 (18.9–27.8) | - |
Male | 526 | 58.2 | 405 | 77.0 (73.2–80.5) | 121 | 23.0 (19.5–26.8) | - |
Charlson comorbidity index | - | - | - | - | - | - | 0.01 |
0 | 621 | 68.7 | 501 | 80.7 (77.5–83.8) | 120 | 19.3 (16.2–22.5) | - |
1–2 | 236 | 26.1 | 164 | 69.5 (64.1–75.6) | 72 | 30.5 (24.4–35.9) | - |
3–4 | 41 | 4.5 | 26 | 63.4 (47.8–78-0) | 15 | 36.6 (22.0–522) | - |
>5 | 6 | 0.7 | 4 | 66.7 (25.0–100.0) | 2 | 33.3 (0.0–75.0) | - |
Autoimmune disease | - | - | - | - | - | - | 0.70 |
Yes | 57 | 6.3 | 45 | 78.9 (68.2–88.9) | 12 | 26.7 (11.1–31.8) | |
No | 847 | 93.7 | 650 | 76.7 (73.7–79.4) | 197 | 23.3 (20.6–26.3) | |
Tumor stage | - | - | - | - | - | - | 0.48 |
IIIA | 81 | 9.0 | 58 | 71.6 (61.7–81.0) | 23 | 28.4 (19.0–38.3) | - |
IIIB | 292 | 32.3 | 226 | 77.4 (72.4–82.2) | 66 | 22.6 (17.8–27-6) | - |
IIIC | 426 | 47.1 | 329 | 77.2 (73.3–81.0) | 97 | 22.8 (19.0–26.7) | - |
IIID | 26 | 2.9 | 23 | 88.5 (75.9–100.0) | 3 | 11.5 (0.0–24.0) | - |
IV | 79 | 8.7 | 59 | 74.7 (64.4–83-8) | 20 | 25.3 (16.2–35.6) | - |
Location of primary | - | - | - | - | - | - | 0.93 |
Head/Neck | 136 | 15.0 | 99 | 72.8 (63.3–80.0) | 37 | 27.2 (20.0–36.2) | - |
Upper extremity | 137 | 15.2 | 107 | 78.1 (70.8–84.3) | 30 | 21.9 (15.7–29.2) | - |
Lower extremity | 218 | 24.1 | 164 | 75.2 (69.6–81.4) | 54 | 24.8 (18.6–30.4) | - |
Trunk | 297 | 32.9 | 232 | 78.1 (73.2–82.5) | 65 | 21.9 (17.5–26.8) | - |
Genital | 13 | 1.4 | 10 | 76.9 (50.0–100.0) | 3 | 23.1 (0.0–50.0) | - |
Acral | 38 | 4.2 | 32 | 84.2 (71.8–94.9) | 6 | 15.8 (5.1–28.2) | - |
Uveal | 3 | 0.3 | 2 | 66.6 (n.e.) | 1 | 33.3 (n.e.) | - |
Other | 9 | 1.0 | 7 | 77.8 (45.6–100.0) | 2 | 22.2 (0.0–54.4) | - |
Unknown | 53 | 5.9 | 42 | 79.2 (69.2–90.0) | 11 | 20.8 (10.0–30.8) | - |
Histological subtype | - | - | - | - | - | - | 0.42 |
Superficial spreading melanoma | 229 | 25.3 | 179 | 78.2 (72.7–83.5) | 50 | 21.8 (16.5–27.3) | |
Nodular melanoma | 278 | 30.8 | 208 | 74.8 (70.0–79.7) | 70 | 25.2 (20.3–30.0) | - |
Acrolentiginous melanoma | 46 | 5.1 | 38 | 82.6 (70.9–92.9) | 8 | 17.4 (7.3–28.3) | - |
Lentigo maligna melanoma | 27 | 3.0 | 17 | 63.0 (44.4–79.3) | 10 | 37.0 (20.7–55.6) | - |
Desmoplastic melanoma | 13 | 1.4 | 7 | 53.8 (25.0–83.3) | 6 | 46.2 (16.7–75.0) | - |
Amelanotic melanoma | 25 | 2.8 | 21 | 84.0 (66.7–96.4) | 4 | 16.0 (3.6–33.3) | - |
Mucosal melanoma | 18 | 2.0 | 14 | 77.8 (55.6–94.7) | 4 | 22.2 (5.3–44.4) | - |
Uveal melanoma | 3 | 0.3 | 2 | 66.7 (n.e.) | 1 | 33.3 (n.e.) | - |
Melanoma of unknown primary | 72 | 8.0 | 56 | 77.8 (68.0–87.3) | 16 | 22.2 (12.7–32.0) | - |
Other/unknown | 193 | 21.3 | 153 | 79.3 (73.6–85.2) | 40 | 20.7 (14.8–26.4) | - |
BRAF mutation status | - | - | - | - | - | - | - |
Mutated | 320 | 35.4 | 267 | 83.4 (79.2–87.3) | 53 | 16.6 (12.7–20.8) | <0.001 |
Wild type | 471 | 52.1 | 354 | 75.2 (71.0–78.8) | 117 | 24.8 (21.2–29.0) | - |
Unknown a | 30 | 3.3 | 22 | 73.3 (57.1–88.2) | 8 | 26.7 (11.8–42.9) | - |
Not specified yet b | 83 | 9.2 | 52 | 62.7 (52.2–72.3) | 31 | 37.3 (27.7–47.8) | - |
Prior intratumoral/adjuvant systemic treatment | - | - | - | - | - | - | 0.002 |
No | 782 | 86.5 | 588 | 75.2 (72.1–78.1) | 194 | 24.8 (21.9–27.9) | - |
Yes | 122 | 13.5 | 107 | 87.7 (81.0–93.4) | 15 | 12.3 (6.6–19.0) | - |
Interferon | 98 | 10.8 | 88 | 89.8 | 10 | 10.2 | - |
Dabrafenib/trametinib | 5 | 0.6 | 4 | 80.0 | 1 | 20.0 | - |
Ipilimumab | 2 | 0.2 | 2 | 100.0 | 0 | 0.0 | - |
Anti-PD1 | 5 | 0.6 | 5 | 100.0 | 0.0 | - | |
Intratumoral injection c | 12 | 1.3 | 8 | 66.7 | 4 | 33.3 | - |
Lymphadenectomy | - | - | - | - | - | - | 0.05 |
Yes | 356 | 39.4 | 291 | 81.7 (77.3–85.6) | 65 | 18.3 (14.4–22.7) | - |
No | 548 | 60.6 | 404 | 73.7 (79.8–77.3) | 144 | 26.3 (22.7–30.2) | - |
Adjuvant radiotherapy | - | - | - | - | - | - | 0.09 |
Yes | 157 | 17.4 | 129 | 82.2 (76.1–88.1) | 28 | 17.8 (11.9–23.9) | - |
No | 747 | 82.6 | 566 | 75.8 (72.6–78.8) | 181 | 24.2 (21.2–27.4) | - |
Region d | - | - | - | - | - | - | 0.49 |
Northern Germany | 444 | 49.1 | 337 | 75.9 (71.9–79.9) | 107 | 24.1 (20.1–28.1) | - |
Southern Germany | 460 | 50.9 | 358 | 77.8 (74.0–81.5) | 102 | 22.2 (18.5–26.0) | - |
Insurance status | - | - | - | - | - | - | 0.15 |
Statutory health insurance | 594 | 65.7 | 446 | 75.1 (71.5–77.5) | 148 | 24.9 (21.5–28.5) | - |
Private health insurance | 127 | 14.0 | 103 | 81.1 (74.3–87.7) | 24 | 18.9 (12.3–25.7) | - |
Insurance status missing | 183 | 20.2 | 146 | 79.8 (74.0–85.7) | 37 | 20.2 (14.3–26.0) | - |
Reasons | Cohort Refusing Adjuvant Treatment | Subgroup of BRAF-Mutated Patients | ||
---|---|---|---|---|
n | % (95% CI) | n | % (95% CI) | |
Total | 218 | - | 59 | - |
Age | 64 | 29.4 (24.4–37.5) | 12 | 20.3 (7.7–28.6) |
Fear of adverse events | 46 | 21.1 (16.3–27.9) | 15 | 25.4 (16.7–41.0) |
Fear of impaired quality of life | 26 | 11.9 (7.4–16.0) | 7 | 11.9 (3.5–21.2) |
Too much effort | 15 | 6.9 (3.5–10.0) | 7 | 11.9 (3.5–21.2) |
Low risk of recurrence (patient opinion) | 11 | 5.0 (2.5–8.8) | 3 | 5.1 (0.0–10.2) |
Time interval between initial diagnosis of melanoma and recurrence | 6 | 2.8 (1.0–5.9) | 2 | 3.4 (0.0–9.3) |
Other reasons | 4 | 1.8 (0.5–4.0) | 1 | 1.7 (0.0–6.4) |
Fear of impaired fertility | 1 | 0.5 (0.0–1.5) | 0 | 0.0 (0) |
No reason mentioned | 45 | 20.6 (17.3–29.0) | 12 | 20.3 (12.5–36.7) |
Exposure Variable | Number of Patients (%) | Adjuvant Treatment | RRadj (95% CI) CC a | RRadj (95% CI) MI a | ||
---|---|---|---|---|---|---|
n | % | n | % | - | - | |
- | 904 | 695 | 76.9 | - | - | |
Age | ||||||
≤65 years (ref.) | 460 | 50.9 | 406 | 88.3 | 1 | - |
>65 years | 444 | 49.1 | 289 | 65.1 | 0.74 (0.68–0.80) | - |
Gender | ||||||
Female (ref.) | 378 | 41.8 | 290 | 76.7 | 1 | - |
Male | 526 | 58.2 | 405 | 77.0 | 1.00 (0.93–1.08) | - |
Charlson comorbidity index | ||||||
0 (ref) | 621 | 68.7 | 501 | 80.7 | 1 | 1 |
≥1 | 283 | 31.3 | 194 | 68.6 | 0.99 (0.92–1.07) | 0.99 (0.93–1.05) |
Tumor stage | ||||||
IIIA (ref.) | 81 | 9.0 | 58 | 71.6 | 1 | 1 |
IIIB | 292 | 32.3 | 226 | 77.4 | 1.06 (0.96–1.16) | 1.04 (0.96–1.13) |
IIIC | 426 | 47.1 | 329 | 77.2 | 1.05 (0.96–1.15) | 1.04 (0.96–1.13) |
IIID | 26 | 2.9 | 23 | 88.5 | 1.07 (0.86–1.34) | 1.07 (0.89–1.30) |
IV b | 79 | 8.7 | 59 | 74.7 | 1.03 (0.90–1.17) | 1.04 (0.93–1.16) |
BRAF status | ||||||
Wild type (ref.) | 471 | 52.1 | 354 | 75.2 | 1 | - |
Mutated | 320 | 35.4 | 267 | 83.4 | 1.02 (0.97–1.07) | - |
Prior intratumoral/adjuvant systemic treatment | ||||||
No (ref.) | 782 | 86.5 | 588 | 75.2 | 1 | 1 |
Yes | 122 | 13.5 | 107 | 87.7 | 1.04 (0.95–1.14) | 1.03 (0.97–1.09) |
Autoimmune disease | ||||||
No (ref.) | 847 | 93.7 | 650 | 76.7 | 1 | - |
Yes | 57 | 6.3 | 45 | 79.0 | 1.00 (0.93–1.08) | - |
Region | ||||||
Northern Germany (ref.) | 444 | 49.1 | 337 | 75.9 | 1 | - |
Southern Germany | 460 | 50.9 | 358 | 77.8 | 1.03 (0.95–1.10) | - |
Insurance status c | ||||||
Statutory health insurance (ref.) | 594 | 65.7 | 446 | 75.1 | 1 | - |
Private health insurance | 127 | 14.0 | 103 | 81.1 | 1.08 (0.98–1.19) | 1.08 (0.98–1.19) |
Characteristics | BRAF-Mutant Patients a | PD-1 Blocker | Targeted Therapy | p-Value b | |||
---|---|---|---|---|---|---|---|
n 263 | % 100 | n 139 | % (95% CI) 52.9 (46.8–59.2) | n 124 | % (95% CI) 47.1 (40.8–53.2) | 0.42 | |
Median age (range) | 56.3 (21.0–87.4) | - | 57.4 (25.8–84.7) | (55–60) | 55.6 (21.0–87.4) | (53–58) | - |
Gender | - | - | - | - | - | - | 0.45 |
Female | 104 | 39.5 | 52 | 50.0 (40.4–60.0) | 52 | 50.0 (40.4–60.0) | - |
Male | 159 | 60.5 | 87 | 54.7 (47.0–62.6) | 72 | 45.3 (37.4–53.0) | - |
Charlson comorbidity index | - | - | - | - | - | - | 0.73 |
0 | 202 | 76.8 | 108 | 53.5 (46.7–60.1) | 94 | 46.5 (39.9–53.3) | - |
1–2 | 54 | 20.5 | 26 | 48.1 (34.5–62.2) | 28 | 51.9 (37.8–65.5) | - |
3–4 | 6 | 2.3 | 4 | 66.7 (n.e.) | 2 | 33.3 (n.e.) | - |
>5 | 1 | 0.4 | 1 | 100.0 (n.e.) | 0 | (n.e.) | - |
Tumor stage | - | - | - | - | - | - | 0.56 |
IIIA | 24 | 9.1 | 14 | 58.3 (37.0–78.3) | 10 | 41.7 (21.7–63.0) | - |
IIIB | 92 | 35.0 | 53 | 57.6 (47.9–68.4) | 39 | 42.4 (31.6–52.1) | - |
IIIC | 136 | 51.7 | 67 | 49.3 (41.2–57.0) | 69 | 50.7 (43.0–58.8) | - |
IIID | 11 | 4.2 | 5 | 45.5 (14.3–75.0) | 6 | 54.5 (25.0–85.7) | - |
IV | 0 | 0.0 | 0 | 0.0 (n.e.) | 0 | 0.0 (n.e.) | - |
Prior intratumoral/adjuvant systemic treatment | - | - | - | - | - | - | 0.02 |
No | 224 | 85.2 | 125 | 55.8 (49.1–62.2) | 99 | 44.2 (37.8–50.9) | - |
Yes | 39 | 14.8 | 14 | 35.9 (21.4–52.6) | 25 | 64.1 (47.4–78.6) | - |
Interferon | 30 | 11.4 | 12 | 40.0 | 18 | 60 | - |
Dabrafenib/trametinib | 3 | 1.1 | 2 | 66.6 | 1 | 33.3 | - |
Ipilimumab | 1 | 0.4 | 0 | 0.0 | 1 | 100 | - |
Anti-PD-1 | 2 | 0.8 | 0 | 0.0 | 2 | 100 | - |
Intratumoral injection c | 3 | 1.1 | 0 | 0.0 | 3 | 100 | - |
Lymphadenectomy | - | - | - | - | - | - | 0.22 |
Yes | 125 | 47.5 | 71 | 56.8 (48.0–65.6) | 54 | 43.2 (34.4–52.0) | - |
No | 138 | 52.5 | 68 | 49.3 (41.2–58.3) | 70 | 50.7 (41.7–58.8) | - |
Adjuvant radiotherapy | - | - | - | - | - | - | 0.11 |
Yes | 42 | 16.0 | 27 | 64.3 (50.0–78.6) | 15 | 35.7 (21.4–50.0) | - |
No | 221 | 84.0 | 112 | 50.7 (43.9–57.3) | 109 | 49.3 (42.7–56.1) | - |
Autoimmune disease | - | - | - | - | - | - | 0.02 |
Yes | 17 | 6.5 | 4 | 23.5 (5.3–46.7) | 13 | 76.5 (53.3–94.7) | - |
No | 246 | 93.5 | 135 | 54.9 (48.5–61.2) | 111 | 45.1 (38.8–51.5) | - |
Region d | - | - | - | - | - | - | <0.01 |
Northern Germany | 142 | 54.0 | 59 | 41.5 (34.2–51.4) | 83 | 58.5 (48.6–65.8) | - |
Southern Germany | 121 | 46.0 | 80 | 66.1 (57.0–74.5) | 41 | 33.9 (25.5–43.0) | - |
Insurance status | - | - | - | - | - | - | 0.43 |
Statutory health insurance | 148 | 56.3 | 73 | 49.3 (41.0–57.7) | 75 | 50.7 (42.3–59.0) | - |
Private health insurance | 42 | 16.0 | 24 | 57.1 (41.0–72.0) | 18 | 42.9 (27.7–59.0) | - |
Insurance status missing | 73 | 27.8 | 42 | 57.5 (45.4–69.0) | 31 | 42.5 (31.0–55.0) | - |
Exposure Variable | Number of Patients (%) | Targeted Therapy | RRadj (95% CI) CC a | RRadj (95% CI) MI a | ||
---|---|---|---|---|---|---|
n | % | n | % | - | - | |
- | 263 | - | 124 | 47.1 | - | - |
Age | ||||||
≤65 years (ref.) | 187 | 71.7 | 89 | 47.6 | 1 | - |
>65 years | 76 | 28.9 | 35 | 46.1 | 0.97 (0.73–1.29) | - |
Gender | ||||||
Female (ref.) | 104 | 39.5 | 52 | 50.0 | 1 | - |
Male | 159 | 60.5 | 72 | 45.3 | 0.91 (0.70–1.17) | - |
Charlson comorbidity index | ||||||
0 (ref) | 202 | 76.8 | 94 | 46.5 | 1 | 1 |
≥1 | 61 | 23.2 | 30 | 49.2 | 1.17 (0.79–1.75) | 1.12 (0.80–1.56) |
Tumor stage | ||||||
IIIA (ref) | 24 | 9.1 | 10 | 41.7 | 1 | 1 |
IIIB | 92 | 35.0 | 39 | 42.4 | 0.76 (0.45–1.26) | 1.05 (0.61–1.80) |
IIIC | 136 | 51.7 | 69 | 50.7 | 1.00 (0.61–1.64) | 1.29 (0.76–2.18) |
IIID | 11 | 4.2 | 6 | 54.6 | 1.09 (0.44–2.72) | 1.46 (0.71–3.03) |
Prior intratumoral/adjuvant systemic treatment | ||||||
No (ref.) | 224 | 85.2 | 99 | 44.2 | 1 | 1 |
Yes | 39 | 14.8 | 25 | 64.1 | 1.24 (0.93–1.68) | 1.24 (0.93–1.68) |
Autoimmune disease c | ||||||
No (ref.) | 246 | 93.5 | 111 | 45.1 | 1 | - |
Yes | 17 | 6.5 | 13 | 76.5 | 1.73 (1.25–2.39) | - |
Region | ||||||
Northern Germany (ref.) | 142 | 54.0 | 83 | 58.5 | 1 | - |
Southern Germany | 121 | 46.0 | 41 | 33.9 | 0.58 (0.44–0.77) | - |
Insurance status b | ||||||
Statutory health insurance (ref.) c | 148 | 56.3 | 75 | 50.7 | 1 | 1 |
Private health insurance | 42 | 16.0 | 18 | 42.9 | 0.85 (0.58–1.24) | 0.81 (0.55–1.20) |
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Lodde, G.; Forschner, A.; Hassel, J.; Wulfken, L.M.; Meier, F.; Mohr, P.; Kähler, K.; Schilling, B.; Loquai, C.; Berking, C.; et al. Factors Influencing the Adjuvant Therapy Decision: Results of a Real-World Multicenter Data Analysis of 904 Melanoma Patients. Cancers 2021, 13, 2319. https://doi.org/10.3390/cancers13102319
Lodde G, Forschner A, Hassel J, Wulfken LM, Meier F, Mohr P, Kähler K, Schilling B, Loquai C, Berking C, et al. Factors Influencing the Adjuvant Therapy Decision: Results of a Real-World Multicenter Data Analysis of 904 Melanoma Patients. Cancers. 2021; 13(10):2319. https://doi.org/10.3390/cancers13102319
Chicago/Turabian StyleLodde, Georg, Andrea Forschner, Jessica Hassel, Lena M. Wulfken, Friedegund Meier, Peter Mohr, Katharina Kähler, Bastian Schilling, Carmen Loquai, Carola Berking, and et al. 2021. "Factors Influencing the Adjuvant Therapy Decision: Results of a Real-World Multicenter Data Analysis of 904 Melanoma Patients" Cancers 13, no. 10: 2319. https://doi.org/10.3390/cancers13102319