Does Risk-Adapted Proton Beam Therapy Have a Role as a Complementary or Alternative Therapeutic Option for Hepatocellular Carcinoma?
Abstract
:1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. Patients
4.2. Treatment
4.3. Evaluation and Statistical Considerations
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Characteristics | Total | Dose-Fx Regimen A | Dose-Fx Regimen B | Dose-Fx Regimen C | p Value | |
---|---|---|---|---|---|---|
n (%) | n (%) | n (%) | n (%) | |||
Gender | Male | 211 (86.8) | 34 (85.0) | 53 (88.3) | 124 (86.7) | 0.888 * |
Female | 32 (13.2) | 6 (15.0) | 7 (11.7) | 19 (13.3) | ||
Age, years | Median (range) | 61 (24–92) | 59 (24–81) | 62.5 (39–80) | 62 (34–92) | 0.133 † |
<60 | 100 (41.2) | 22 (55.0) | 24 (40.0) | 54 (37.8) | 0.144 * | |
≥60 | 143 (58.8) | 18 (45.0) | 36 (60.0) | 89 (62.2) | ||
ECOG PS | 0 | 237 (97.5) | 38 (95.0) | 59 (98.3) | 140 (97.9) | 0.520 * |
1 | 6 (2.5) | 2 (5.0) | 1 (1.7) | 3 (2.1) | ||
Etiology of LC | HBV | 188 (77.4) | 33 (82.5) | 45 (75.0) | 110 (76.9) | 0.799 * |
HCV | 20 (8.2) | 3 (7.5) | 6 (10.0) | 11 (7.7) | ||
Alcoholic | 17 (7.0) | 1 (2.5) | 6 (10.0) | 10 (7.0) | ||
Unknown | 18 (7.4) | 3 (7.5) | 3 (5.0) | 12 (8.4) | ||
Child-Pugh | A | 228 (93.8) | 36 (90.0) | 54 (90.0) | 138 (96.5) | 0.117 * |
Classification | B7 | 15 (6.2) | 4 (10.0) | 6 (10.0) | 5 (3.5) | |
AFP, ng/mL | Median (range) | 10.2 (1.2–38,396.4) | 25.3 (1.9–31,466.3) | 10.9 (2.2–38,396.4) | 9.3 (1.2–16,788.3) | 0.062 † |
<10 | 120 (49.4) | 14 (35.0) | 30 (50.0) | 76 (53.1) | 0.127 * | |
≥10 | 123 (50.6) | 26 (65.0) | 30 (50.0) | 67 (46.9) | ||
Tumor size, cm | Median (range) | 2.2 (1.0–17) | 6.0 (1.3–17) | 3.6 (1.0–12) | 1.5 (1.0–12.7) | <0.001 † |
≤2 | 115 (47.3) | 1 (2.5) | 16 (26.7) | 98 (68.5) | <0.001 * | |
>2 | 128 (52.7) | 39 (97.5) | 44 (73.3) | 45 (31.5) | ||
TVT | No | 184(75.7) | 11 (27.5) | 40 (66.7) | 133 (93.0) | <0.001 * |
Branch | 29 (11.9) | 7 (17.5) | 15 (25.0) | 7 (4.9) | ||
Main | 30 (12.3) | 22 (55.0) | 5 (8.3) | 3 (2.1) | ||
mUICC stage | I | 13 (5.3) | 1 (2.5) | 2 (3.3) | 10 (7.0) | <0.001 * |
II | 74 (30.5) | 1 (2.5) | 13 (21.7) | 60 (42.0) | ||
III | 106 (43.6) | 12 (30.0) | 31 (51.7) | 63 (44.1) | ||
IVA | 50 (20.6) | 26 (65.0) | 14 (23.3) | 10 (7.0) | ||
BCLC stage | A | 97 (39.9) | 0 (0) | 17 (28.3) | 80 (55.9) | <0.001 * |
B | 86 (35.4) | 11 (27.5) | 22 (36.7) | 53 (37.1) | ||
C | 60 (24.7) | 29 (72.5) | 21 (35.0) | 10 (7.0) | ||
Diagnosis at PBT | Primary | 10 (4.1) | 5 (12.5) | 2 (3.3) | 3 (2.1) | 0.021 |
Recurrence | 233 (95.9) | 35 (87.5) | 58 (96.7) | 140 (95.9) | ||
Pre-Tx to PBT site | No | 52 (21.4) | 7 (17.5) | 4 (6.7) | 41 (28.7) | 0.002 * |
Yes | 191 (78.6) | 33 (82.5) | 56 (93.3) | 102 (71.3) | ||
LRT | 186 (97.4) | 27 (81.8) | 54 (96.4) | 102 (97.4) | ||
LRT + sorafenib | 5 (2.6) | 3 (9.1) | 2 (3.6) | 0 (0) | ||
Sorafenib ± chemo | 3 (1.6) | 3 (9.1) | 0 (0) | 0 (0) | ||
Pre-Tx to other site | No | 70 (28.8) | 22 (55.0) | 23 (38.3) | 25 (17.5) | <0.001 * |
Yes | 173 (43.9) | 18 (45.0) | 37 (61.7) | 118 (82.5) | ||
LRT | 171 (98.3) | 18 (100) | 36 (97.3) | 117 (98.3) | ||
LRT + sorafenib | 3 (1.7) | 0 (0) | 1 (2.7) | 2 (1.7) | ||
Concurrent Tx | No | 236 (97.1) | 34 (85.0) | 59 (98.3) | 143 (100) | <0.001 * |
Sorafenib | 7 (2.9) | 6 (15.0) | 1 (1.7) | 0 (0) | ||
Post-Tx to PBT site | No | 195 (80.2) | 12 (30.0) | 48 (80.0) | 135 (94.4) | <0.001 * |
Yes | 48 (19.8) | 28 (70.0) | 12 (20.0) | 8 (5.6) | ||
LRT | 16 (33.3) | 7 (25.0) | 7 (58.3) | 2 (25.0) | ||
LRT ± sorafenib ± chemo | 7 (14.6) | 6 (21.4) | 0 (0) | 1 (12.5) | ||
Sorafenib ± chemo | 25 (52.1) | 15 (53.6) | 5 (41.7) | 5 (62.5) | ||
Post-Tx to other site | No | 66 (27.2) | 8 (20.0) | 18 (30.0) | 40 (28.0) | 0.515 * |
Yes | 177 (72.8) | 32 (80.0) | 42 (70.0) | 103 (72.0) | ||
LRT | 91 (51.7) | 4 (12.5) | 19 (45.2) | 68 (66.0) | ||
LRT ± sorafenib ± chemo | 57 (32.4) | 17 (51.1) | 15 (35.7) | 26 (25.2) | ||
Sorafenib ± chemo | 28 (15.9) | 11 (34.4) | 8 (19.0) | 9 (8.7) |
Response | Dose-Fractionation Regimen, n (%) | p Value * | Pre-Tx to PBT Site, n (%) | p Value * | Post-Tx to PBT Site, n (%) | p Value * | |||||
---|---|---|---|---|---|---|---|---|---|---|---|
Regimen A | Regimen B | Regimen C | No | Yes | No | Yes | |||||
Primary tumor | CR | 16 (40.0) | 51 (85.0) | 132 (92.3) | <0.001 | 47 (90.4) | 152 (79.6) | 0.405 | 174 (89.2) | 25 (53.1) | <0.001 |
(n = 243) | PR | 18 (45.0) | 6 (10.0) | 6 (4.2) | 4 (7.7) | 26 (13.6) | 16 (8.2) | 14 (29.2) | |||
SD | 6 (15.02) | 2 (3.3) | 5 (3.5) | 1 (1.9) | 12 (6.3) | 5 (2.6) | 1 (2.1) | ||||
PD | 0 (0.0) | 1 (1.7) | 0 (0.0) | 0 (0.0) | 1 (0.5) | 0 (0.0) | 1 (2.1) | ||||
TVT | CR | 9 (31.0) | 15 (75.0) | 6 (60.0) | 0.021 | 3 (42.9) | 27 (51.9) | 0.877 | 15 (60.0) | 15 (44.1) | 0.610 |
(n = 59) | PR | 12 (41.4) | 3 (15.0) | 3 (30.0) | 3 (42.9) | 15 (28.9) | 7 (28.0) | 11 (32.4) | |||
SD | 8 (27.6) | 1 (5.0) | 1 (10.0) | 1 (14.2) | 9 (17.3) | 3 (12.0) | 7 (20.6) | ||||
PD | 0 (0.0) | 1 (5.0) | 0 (0.0) | 0 (0.0) | 1 (1.9) | 0 (0.0) | 1 (2.9) |
Characteristics | Univariate † | Multivariate ‡ | ||||||
---|---|---|---|---|---|---|---|---|
1-yr OS, % (95% CI) | 3-yr OS, % (95% CI) | 5-yr OS, % (95% CI) | Median OS, Months (95% CI) | p Value | Hazard Ratio (95% CI) | p Value | ||
Gender | Male | 87.7 (83.2–92.2) | 62.2 (55.1–69.3) | 48.3 (38.5–58.1) | 56.5 (45.5–67.2) | 0.964 | - | NS |
Female | 96.9 (90.8–100) | 60.2 (42.6–77.8) | 49.3 (29.3–69.3) | 46.6 (-) | - | |||
Age, years | <60 | 88.0 (81.7–94.3) | 63.3 (53.3–73.3) | 45.0 (29.1–60.9) | 56.5 (35.1–77.9) | 0.945 | - | NS |
≥60 | 89.5 (84.4–94.6) | 60.8 (52.0–69.6) | 49.5 (38.3–60.7) | 55.0 (44.5–65.5) | - | |||
ECOG PS | 0 | 88.6 (84.5–92.7) | 62.8 (56.1–69.5) | 48.6 (39.4–57.8) | 56.5 (44.9–68.0) | 0.175 | - | NS |
1 | 100 (-) | 25.0 (0–65.0) | - (-) | 21.2 (4.1–38.4) | - | |||
Etiology of LC | HBV | 88.8 (84.3–93.3) | 62.4 (55.0–69.8) | 49.4 (39.2–59.6) | 56.5 (-) | 0.784 | - | NS |
Others | 89.1 (80.9–97.3) | 60.0 (45.5–74.5) | 44.9 (26.1–63.7) | 55.0 (32.0–78.0) | - | |||
Child-Pugh Classification | A | 90.4 (86.5–94.3) | 65.3 (58.6–72.0) | 50.5 (41.1–59.9) | 60.3 (-) | <0.001 | 1.000 | 0.016 |
B7 | 66.7 (42.8–90.6) | 0.91 (0–26.0) | 0.91 (0–26.0) | 17.1 (1.6–32.6) | 2.221 (1.162–4.246) | |||
AFP, ng/mL | <10 | 92.5 (87.8–97.2) | 74.3 (65.7–82.9) | 56.3 (41.6–71.0) | NR | <0.001 | 1.000 | 0.008 |
≥10 | 85.4 (79.1–91.7) | 49.9 (40.5–59.3) | 39.6 (28.6–50.6) | 34.3 (24.4–44.2) | 1.773 (1.158–2.713) | |||
Tumor size, cm | ≤2 | 94.8 (90.7–98.9) | 79.5 (71.5–87.5) | 64.4 (49.3–7.5) | NR | <0.001 | - | NS |
>2 | 83.6 (77.1–90.1) | 46.5 (37.1–55.9) | 34.0 (23.6–44.4) | 33.9 (28.4–39.5) | - | |||
TVT | No | 93.5 (90.0–97.0) | 67.8 (60.4–75.3) | 54.1 (43.9–64.3) | 60.3 (-) | <0.001 | – | NS |
Branch | 79.3 (60.4–91.4) | 49.0 (29.8–68.2) | 49.0 (29.8–68.2) | 34.3 (-) | ||||
Main | 73.3 (57.4–89.2) | 38.8 (21.0–56.6) | 18.9 (0–38.1) | 19.4 (6.1–32.8) | - | |||
mUICC stage | I | 100 (-) | 92.3 (77.8–100) | 69.2 (28.6–100) | NR | <0.001 | 1.000 | |
II | 94.6 (89.5–99.7) | 83.9 (74.5–93.3) | 65.4 (45.8–85) | NR | 3.186 (0.699–14.525) | 0.134 | ||
III | 93.4 (88.7–98.1) | 57.0 (46.8–67.2) | 43.8 (31.3–56.3) | 46.6 (34.9–58.4) | 6.563 (1.557–27.669) | 0.010 | ||
IVA | 68.0 (55.1–80.9) | 33.4 (19.7–47.1) | 26.6 (12.7–40.5) | 19.4 (10.0–28.8) | 7.119 (1.673–30.288) | 0.008 | ||
BCLC stage | A | 96.9 (93.4–100) | 80.1 (71.5–88.7) | 65.1 (50.2–80.0) | NR | <0.001 | - | NS |
B | 89.5 (83.0–96.0) | 53.9 (42.3–65.5) | 40.0 (26.1–53.9) | 37.1 (24.2–50.1) | - | |||
C | 75.0 (64.0–86.0) | 44.6 (31.5–57.7) | 32.2 (16.0–48.6) | 33.9 (16.2–51.7) | - | |||
Diagnosis at PBT | Primary | 90.0 (71.4–100) | 56.0 (22.5–89.5) | 42.0 (7.5–76.5) | 38.4 (8.5–68.2) | 0.578 | - | NS |
Recurrence | 88.8 (83.8–92.1) | 62.0 (55.3–68.7) | 48.2 (38.8–57.6) | 56.5 (45.3–67.7) | - | |||
Pre-Tx to PBT site | No | 98.1 (94.4–100) | 82.3 (71.1–93.5) | 78.4 (65.3–91.5) | NR | <0.001 | - | NS |
Yes | 86.4 (81.5–91.3) | 56.8 (49.4–64.2) | 41.7 (32.1–51.3) | 46.9 (33.7–60.1) | - | |||
Pre-Tx to other site | No | 87.1 (79.3–94.9) | 54.0 (41.3–66.7) | 41.4 (26.3–56.5) | 38.4 (19.7–57.1) | 0.130 | - | NS |
Yes | 89.6 (85.1–94.1) | 64.9 (57.3–72.5) | 51.2 (39.8–62.5) | NR | - | |||
Concurrent Tx | No | 89.8 (85.9–93.7) | 62.8 (56.1–69.5) | 49.4 (38.0–60.8) | 56.5 (-) | 0.001 | - | NS |
Sorafenib | 57.1 (20.4–93.8) | 28.6 (0–62.1) | 0 (-) | 19.4 (0–40.3) | - | |||
Post-Tx to PBT site | No | 93.8 (90.5–97.1) | 67.5 (60.2–74.8) | 53.8 (42.6–65.0) | 60.3 (-) | <0.001 | - | NS |
Yes | 68.7 (55.6–81.8) | 40.2 (25.9–54.5) | 26.2 (12.5–39.9) | 25.4 (7.1–43.7) | - | |||
Post-Tx to other sites | No | 81.8 (72.6–91.0) | 68.8 (56.8–80.8) | 61.9 (45.2–78.6) | NR | 0.294 | - | NS |
Yes | 91.5 (87.3–95.6) | 59.8 (52.2–67.4) | 44.3 (34.1–54.5) | 48.7 (36.3–61.1) | - | |||
Dose-fractionation | Regimen A | 75.0 (61.7–88.3) | 33.3 (18.4–48.2) | 16.7 (3.6–29.8) | 23.4 (15.3–31.5) | <0.001 | 2.045 (1.244–3.362) | 0.005 |
Regimen B | 86.7 (78.1–95.3) | 51.2 (38.1–64.3) | 39.2 (24.9–53.5) | 40.8 (19.7–61.9) | 1.298 (0.740–2.277) | 0.363 | ||
Regimen C | 93.7 (89.8–97.6) | 76.0 (68.4–83.6) | 67.9 (57.5–78.3) | NR | 1.000 | |||
Primary tumor response | CR | 97.0 (94.6–99.4) | 73.3 (66.6–80.0) | 60.9 (51.5–70.3) | NR | <0.001 | 1.000 | <0.001 |
Non-CR | 52.3 (37.6–67.0) | 10.6 (1.0–20.2) | 0 (-) | 13.7 (10.8–16.6) | 7.012 (4.324–11.370) |
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Kim, T.H.; Park, J.-W.; Kim, B.H.; Kim, H.; Moon, S.H.; Kim, S.S.; Woo, S.M.; Koh, Y.-H.; Lee, W.J.; Kim, D.Y.; et al. Does Risk-Adapted Proton Beam Therapy Have a Role as a Complementary or Alternative Therapeutic Option for Hepatocellular Carcinoma? Cancers 2019, 11, 230. https://doi.org/10.3390/cancers11020230
Kim TH, Park J-W, Kim BH, Kim H, Moon SH, Kim SS, Woo SM, Koh Y-H, Lee WJ, Kim DY, et al. Does Risk-Adapted Proton Beam Therapy Have a Role as a Complementary or Alternative Therapeutic Option for Hepatocellular Carcinoma? Cancers. 2019; 11(2):230. https://doi.org/10.3390/cancers11020230
Chicago/Turabian StyleKim, Tae Hyun, Joong-Won Park, Bo Hyun Kim, Hyunjung Kim, Sung Ho Moon, Sang Soo Kim, Sang Myung Woo, Young-Hwan Koh, Woo Jin Lee, Dae Yong Kim, and et al. 2019. "Does Risk-Adapted Proton Beam Therapy Have a Role as a Complementary or Alternative Therapeutic Option for Hepatocellular Carcinoma?" Cancers 11, no. 2: 230. https://doi.org/10.3390/cancers11020230