Radiotherapy in Combination with Systemic Therapy for Multiple Myeloma—A Critical Toxicity Evaluation in the Modern Treatment Era
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Clinical Data
2.2. Statistical Analysis
3. Results
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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Patient Characteristics | n (% or Range) |
---|---|
Number of Patients | 82 |
Sex | |
Male | 50 (61) |
Female | 32 (39) |
Median age at diagnosis, y | 58.5 (39–85) |
Median time to RT, m | 1 (0–86) |
R-ISS at initial diagnosis | |
I | 17 (20.7) |
II | 44 (53.7) |
III | 5 (6.1) |
Not recorded | 16 (19.5) |
ECOG Performance Status | |
0 | 14 (17.1) |
1 | 27 (32.9) |
2 | 7 (8.5) |
3 | 5 (6.1) |
4 | 0 |
Not recorded | 29 (35.4) |
Localization | |
Spine | 80 (97.6) |
Pelvis | 58 (70.7) |
Extremities | 31 (37.8) |
Skull | 32 (39.0) |
Rib cage | 35 (42.7) |
Shoulders | 17 (20.7) |
Treatment Characteristics | n (%) |
---|---|
Prior surgery | |
Yes | 36 (43.9) |
No | 46 (56.1) |
Type of surgery | |
Biopsy | 17 (47.2) |
Osteosynthesis | 18 (50.0) |
Laminectomy | 7 (19.4) |
Resection | 5 (13.9) |
Anti-myeloma agents applied within 30 days prior to 90 days after RT * | |
PI | 56 (68.3) |
IMiD | 32 (39.0) |
Glucocorticoid | 72 (87.8) |
Alkylating Agent | 35 (42.7) |
Topoisomerase Inhibitor | 16 (19.5) |
Others | 4 (4.9) |
Anti-myeloma agents within concurrent systemic therapy ** | |
PI | 39 (47.6) |
IMiD | 16 (19.5) |
Glucocorticoid | 53 (64.6) |
Alkylating Agent | 12 (14.6) |
Topoisomerase Inhibitor | 2 (2.4) |
Others | 1 (1.2) |
Time range of systemic therapy *** | |
Up to 30 d before | 39 (47.6) |
30 d before | 10 (12.2) |
14 d before | 22 (26.8) |
7 d before | 31 (37.8) |
<7 d before | 36 (43.9) |
During | 53 (64.6) |
Up to 90 d after | 75 (91.5) |
14 d after | 61 (74.4) |
30 d after | 67 (81.7) |
90 d after | 60 (73.2) |
Stem Cell Mobilization | 13 (15.9) |
Auto-SCT | 8 (9.8) |
Osteoprotection | 68 (82.9) |
Radiotherapy Characteristics | n (% of PTV or Range) |
---|---|
PTV | |
Number | 134 |
Per patient | 1 (1–4) |
Irradiated bones per patient | 5 (1–14) |
Dose-category | |
<20 Gy | 1 (0.7) |
20-40 Gy | 75 (56.0) |
>40 Gy | 51 (38.1) |
Not recorded | 7 (5.2) |
Fractions | 20 (4–33) |
Dose per Fraction | 2 Gy (1.8–3 Gy) |
Technique | |
2D | 8 (6.0) |
3D-CRT | 54 (40.3) |
IMRT, Sliding-Window-technique | 41 (30.6) |
IMRT, VMAT | 18 (13.4) |
Tomotherapy | 3 (2.2) |
Not recorded | 10 (7.5) |
Localization * | |
Spine | 95 (70.9) |
Pelvis | 34 (25.4) |
Extremities | 3 (2.2) |
Skull | 2 (1.5) |
Ribcage | 6 (4.5) |
Shoulder | 3 (2.2) |
Non-Hematological Toxicity and Grade | Total (n = 82) | RT (n = 29) | RT/ST (n = 53) | p |
---|---|---|---|---|
Any Non-Hematological Toxicity * | ||||
Any grade | 54 (65.9) | 19 (65.5) | 35 (66) | 1.000 |
Low-grade | 50 (61.0) | 19 (65.5) | 31 (58.5) | 0.638 |
High-grade | 14 (17.1) | 6 (20.7) | 8 (15.1) | 0.550 |
Fatigue | 0.735 | |||
Low-grade | 18 (22.0) | 6 (20.7) | 12 (22.6) | |
High-grade | 1 (1.2) | 0 | 1 (1.9) | |
Skin | 0.718 | |||
Low-grade | 27 (32.9) | 9 (31.0) | 18 (34.0) | |
High-grade | 1 (1.2) | 0 | 1 (1.9) | |
Gastrointestinal | 0.251 | |||
Low-grade | 11 (13.4) | 2 (6.9) | 9 (17.0) | |
High-grade | 3 (3.7) | 2 (6.9) | 1 (1.9) | |
Mucosa | 0.814 | |||
Low-grade | 11 (13.4) | 4 (13.8) | 7 (13.2) | |
High-grade | 4 (4.9) | 2 (6.9) | 2 (3.8) | |
Nausea | 1.000 | |||
Low-grade | 10 (12.2) | 3 (10.3) | 7 (13.2) | |
High-grade | 0 | 0 | 0 | |
Vomiting | 1.000 | |||
Low-grade | 2 (2.4) | 1 (3.4) | 1 (1.9) | |
High-grade | 0 | 0 | 0 | |
Pulmonary | 0.524 | |||
Low-grade | 2 (2.4) | 1 (3.4) | 1 (1.9) | |
High-grade | 2 (2.4) | 0 | 2 (3.8) | |
Neurologic | 0.233 | |||
Low-grade | 4 (4.9) | 0 | 4 (7.5) | |
High-grade | 1 (1.2) | 0 | 1 (1.9) | |
Musculoskeletal | 1.000 | |||
Low-grade | 1 (1.2) | 0 | 1 (1.9) | |
High-grade | 0 | 0 | 0 | |
Other | 0.819 | |||
Low-grade | 6 (7.3) | 2 (6.9) | 4 (7.5) | |
High-grade | 4 (4.9) | 2 (6.9) | 2 (3.8) |
Hematological Toxicity | Time | Grade | Total | RT | RT/ST | p |
---|---|---|---|---|---|---|
Before RT | No Toxicity | 15 (18.3) | 5 (17.2) | 10 (18.9) | 0.982 | |
Low-Grade | 42 (51.2) | 13 (44.8) | 29 (54.7) | |||
High-Grade | 6 (7.3) | 2 (6.9) | 4 (7.5) | |||
Not recorded | 19 (23.2) | 9 (31.0) | 10 (18.9) | |||
Anemia | During RT | No Toxicity | 5 (6.1) | 2 (6.9) | 3 (5.7) | 0.474 |
Low-Grade | 50 (61.0) | 16 (55.2) | 34 (64.2) | |||
High-Grade | 8 (9.8) | 1 (3.4) | 7 (13.2) | |||
Not recorded | 19 (23.2) | 10 (34.5) | 9 (17.0) | |||
After RT | No Toxicity | 2 (2.4) | 1 (3.4) | 1 (1.9) | 0.532 | |
Low-Grade | 55 (67.1) | 18 (62.1) | 37 (69.8) | |||
High-Grade | 11 (13.4) | 2 (6.9) | 9 (17.0) | |||
Not recorded | 14 (17.1) | 8 (27.6) | 6 (11.3) | |||
Before RT | No Toxicity | 50 (61.0) | 13 (44.8) | 37 (69.8) | 0.255 | |
Low-Grade | 10 (12.2) | 5 (17.2) | 5 (9.4) | |||
High-Grade | 1 (1.2) | 0 | 1 (1.9) | |||
Not recorded | 21 (25.6) | 11 (37.9) | 10 (18.9) | |||
Thrombocytopenia | During RT | No Toxicity | 33 (40.2) | 12 (41.4) | 21 (39.6) | 0.184 |
Low-Grade | 26 (31.7) | 6 (20.7) | 20 (37.7) | |||
High-Grade | 1 (1.2) | 1 (3.4) | 0 | |||
Not recorded | 22 (26.8) | 10 (34.5) | 12 (22.6) | |||
After RT | No Toxicity | 14 (17.1) | 8 (27.6) | 6 (11.3) | 0.063 | |
Low-Grade | 38 (46.3) | 9 (31.0) | 29 (54.7) | |||
High-Grade | 15 (18.3) | 4 (13.8) | 11 (20.8) | |||
Not recorded | 15 (18.3) | 8 (27.6) | 7 (13.2) | |||
Before RT | No Toxicity | 47 (57.3) | 14 (48.3) | 33 (62.3) | 0.806 | |
Low-Grade | 13 (15.9) | 4 (13.8) | 9 (17.0) | |||
High-Grade | 1 (1.2) | 0 | 1 (1.9) | |||
Not recorded | 21 (25.6) | 11 (37.9) | 10 (18.9) | |||
Leukocytopenia | During RT | No Toxicity | 22 (26.8) | 6 (20.7) | 16 (30.2) | 0.684 |
Low-Grade | 31 (37.8) | 11 (37.9) | 20 (37.7) | |||
High-Grade | 9 (11.0) | 2 (6.9) | 7 (13.2) | |||
Not recorded | 20 (24.4) | 10 (34.5) | 10 (18.9) | |||
After RT | No Toxicity | 18 (22.0) | 7 (24.1) | 11 (20.8) | 0.042 | |
Low-Grade | 22 (26.8) | 10 (34.5) | 12 (22.6) | |||
High-Grade | 28 (34.1) | 4 (13.8) | 24 (45.3) | |||
Not recorded | 14 (17.1) | 8 (27.6) | 6 (11.3) |
Study | n | Median FU (m) | Dose (Gy) | IMRT * (%) | Novel Agent (%) | Non-Hematological Toxicity (Any grade) | Hematological Toxicity (Grade III or IV) |
---|---|---|---|---|---|---|---|
Shin et al., 2014 [17] | 39 | 6 | 8–37.5 (Mean 26.8) | n.a. | 43.6% | 23.8–40% ** | n.a. |
Salgado et al., 2019 [18] | 130 | 14 | 2–40 (Median 20) | 15.4% | 70% | 45.9% | n.a. |
Guerini et al., 2022 [19] | 312 | n.a. | 8–30 | 3.5% | 48.7% | 41% | n.a. |
Nehlsen et al., 2022 [20] | 55 | 59.8 | 8–32.5 (Median 20) | n.a. | 40% | 14.6% | 35% |
Present study | 82 | 46.5 | 8–59 (Median 40) | 46.3% | 85.4% | 65.9% | 45.1% |
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Oertel, M.; Schlusemann, T.; Shumilov, E.; Reinartz, G.; Bremer, A.; Rehn, S.; Lenz, G.; Khandanpour, C.; Eich, H.T. Radiotherapy in Combination with Systemic Therapy for Multiple Myeloma—A Critical Toxicity Evaluation in the Modern Treatment Era. Cancers 2023, 15, 2909. https://doi.org/10.3390/cancers15112909
Oertel M, Schlusemann T, Shumilov E, Reinartz G, Bremer A, Rehn S, Lenz G, Khandanpour C, Eich HT. Radiotherapy in Combination with Systemic Therapy for Multiple Myeloma—A Critical Toxicity Evaluation in the Modern Treatment Era. Cancers. 2023; 15(11):2909. https://doi.org/10.3390/cancers15112909
Chicago/Turabian StyleOertel, Michael, Tom Schlusemann, Evgenii Shumilov, Gabriele Reinartz, Anne Bremer, Stephan Rehn, Georg Lenz, Cyrus Khandanpour, and Hans Theodor Eich. 2023. "Radiotherapy in Combination with Systemic Therapy for Multiple Myeloma—A Critical Toxicity Evaluation in the Modern Treatment Era" Cancers 15, no. 11: 2909. https://doi.org/10.3390/cancers15112909