The Current Role of Radiation in the Management of Cholangiocarcinoma—A Narrative Review
Abstract
:Simple Summary
Abstract
1. Introduction
2. Unresectable or Inoperable CCA
3. Preoperative Radiation and Transplantation
Preoperative Radiation and Resection
4. Postoperative Radiation
5. Combined Immunotherapy and Radiotherapy
6. Systemic Treatment in CCA
6.1. Neoadjuvant Chemotherapy
6.2. Adjuvant Chemotherapy
6.3. Advanced/Metastatic Cholangiocarcinoma
7. Highlighting Current Trials and Future Trials
8. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Author, Year | n | Site | Intervention | Control | Median OS (Months) | Median PFS (Months) |
---|---|---|---|---|---|---|
Phelip et al., 2014 [6] | 34 | CCA, GB | 50Gy RT, 5-FU, Cis | GEMOX | OS: 13.5, 19.9 | PFS: 5.8, 11 |
Tse et al., 2008 [7] | 10, 31 | iCCA, HCC | SBRT: 24–54 Gy, median 36 Gy, 6 fractions in 2 weeks | n.a. | IHCC: MST: 15; 1yrLC: 65%; 1yrOS: 58%. | n.r. |
Frakulli et al., 2019 [8] | 231 | CCA | SBRT: variable | n.a. | OS: 15; 1yr: 58.3%; 2yr: 35.5%. 1yrLC: 83.4% | n.r. |
Kopek et al., 2010 [9] | 27 | CCA | SBRT: 45 Gy in 3 fractions | n.a. | OS: 10.6 | PFS: 6.7 |
Jung et al., 2014 [10] | 58 | CCA | Primary CCA; SBRT: 15–60 Gy in 1–5 fractions, median 45 Gy in 3 fractions | Same for recurrent | Overall: OS: 10; 1yr: 45%; 2yr: 20%; LC: 1yr: 85%; 2yr: 72%. Respective: OS: 5, 13. | 1yrPFS: 26%; 2yrPFS: 23%. |
Kozak et al., 2020 [11] | 40 | CCA | SBRT: 40Gy in 1–5 fractions | n.a. | OS: 23 1yrOS: 69%, 2yrOS:39% | n.r. |
Baak et al., 2021 [12] | 6 | eCCA | After CTX (GEMCIS), SBRT: 60 Gy; 15 fractions of 3–4.5 Gy | n.a. | 1yrLC: 80% 1yrOS: 100% | PFS: 14 |
Gkika et al., 2017 [13] | 37 | CCA | SBRT: median 45 Gy (25–66 Gy) in 3–12 fractions | n.a. | OS: 14 1yrOS: 56%; 1yrLC:78% | PFS: 9 |
Polistina et al., 2011 [14] | 10 | eCCA | SBRT + Gem: 30Gy in 3 fractions | n.a. | 2yrOS: 80% 4yrOS: 30% | TTP: 30 |
Zhang et al., 2023 [15] | 43 | iCCA | Cyber Knife SBRT | n.a. | OS: 12; 1yrOS: 51.2%; 2yrOS: 32.6%; 3yrOS: 23.3% | PFS: 6 |
Chen et al., 2010 [5] | 84 | iCCA | EBRT: 30–60 Gy in fractions of 1.8–2.0 Gy daily; median 50 Gy | No EBRT (n = 49) | MST: 9.5, 5.1 1yrSR: 38.5%, 16.4%; 2yrSR: 9.6%, 4.9% | n.r. |
Boothe et al., 2016 [16] | 1326 | eCCA | EBRT: variable | EBRT, brachytherapy | OS: 9, 11. | n.r. |
Hong et al., 2016 [17] | 37, 44 + 2 | iCCA, HCC | PBT: max dose 67.5 Gy in 15 fractions, median 58 Gy | n.a. | IHCC: OS: 22.5; 8.4; 1yrOS: 69.7%; 2yrOS: 46.5%. | PFS: 1yr: 41.4%; 2yr: 25.7% |
Hung et al., 2020 [18] | 30 | CCA | PBT: median 72.6 Gy; concurrent CTX (n = 23) | n.a. | OS: 19.3; 1yrLC: 88%; 1yrRC: 86%; 1yrDC: 68% | PFS: 10.4 |
Yu et al., 2021 [19] | 443, 732 | iCCA | EBRT: variable | SIRT: variable | MST: 13.6, 12 | n.r. |
Edeline et al., 2021 [20] | 3990 | iCCA | Pooled analysis of SIRT, TACE, HAI, EBRT | n.a. | EBRT: 18.9, SIRT: 14.1 | EBRT: 15.6, SIRT:7.8 |
Kumar et al., 2022 [21] | 16 | iCCA | SIRT (min 190 Gy) | n.a. | OS: 7 | n.r. |
Cucchetti et al., 2017 [22] | 224 | iCCA | SIRT | Addition of CTX | MST: 19.5, 5.5 | n.r. |
Manceau et al., 2018 [23] | 40 | iCCA | SIRT (mean 322 Gy), CTX (25 mg/m2 Cis and 1000 mg/m2 Gem days 1 and 8, every 3 weeks; 50 mg/m2 Cis and 5-FU at 400 mg/m2 on day 1, 5-FU 2400 mg/m2, every 2 weeks; 1000 mg/m2 Gem on day 1, 100 mg/m2 Ox either day 1/2, every 2 weeks; Gem reduced to 300 mg/m2 around SIRT) | n.a. | OS: 28.6 | PFS: 12.7 |
Edeline et al., 2020 [24] | 41 | iCCA | SIRT (120 Gy), Cis (25 mg/m2), Gem (1000 mg/m2, reduced to 300 mg/m2 just before and after SIRT, on days 1 and 8 (21-day cycle, for 8 cycles). | n.a. | OS: 22 | PFS: 14 |
Chan et al., 2022 [25] | 24 | iCCA | SIRT (120 Gy) (n = 24), cis (25 mg/m2), gem (1000 mg/m2) on days 1 and 8 (n = 16). | n.a. | OS: 13.6 CTX OS: 21.6 | CTX PFS: 9 |
Tao et al., 2016 [26] | 79 | iCCA | CTX, then 3D-CRT: 35–100 Gy, median 58.05 Gy in 3–30 fractions (BED 43.75–180 Gy, median 80.5 Gy) | n.a. | BED > 80.5 Gy vs <: 3yrOS: 73%, 38%; 3yrLC: 78%, 45%. | n.r. |
Author, Year | n | Site | Treatment | Comparison | Median OS (Months or %) | Median PFS (Months or %) |
---|---|---|---|---|---|---|
Heimbach et al., 2004 [28] | 56 | eCCA | Neoadjuvant EBRT (45 Gy in 30 fractions, 2 Gy/fraction), brachytherapy (I192-20–30 Gy, 2–3 weeks after EBRT), 5-FU (500 mg/m2 daily for 3 days [EBRT], 225 mg/m2 daily [brachytherapy]), Cap (2000 mg/m2/day in 2 divided doses, 2/3 weeks), then transplant | n.a. | 5yrSR: 54%, 64% (48 operatively staged), 84% (34 with negative staging operations); 1yrSR transplant: 88%; 2yrSR transplant: 82% | n.r. |
Azad et al., 2020 [29] | 237 | hCCA | Neoadjuvant EBRT (45 Gy in 30 fractions, 2 Gy/fraction), brachytherapy (I192- 20–30 Gy, 2–3 weeks after EBRT), 5-FU (500 mg/m2 daily for 3 days [EBRT], 225 mg/m2 daily [brachytherapy]), Cap (2000 mg/m2/day in 2 divided doses, 2/3 weeks), then transplant | De novo/PSC | 1yrSR: 92%, 5yr SR: 68%, 10yr SR: 60%. De novo: 1yrSR: 91%, 5yr SR: 58%, 10yr SR: 49%. PSC: 1yrSR: 93%, 5yr SR: 74%, 10yr SR: 67%. | n.r. |
Murad et al., 2012 [30] | 287 | eCCA | EBRT (99%) (45 Gy), brachytherapy (75%) (20 Gy), radio-sensitizing therapy (98%), and/or CTX (65%), transplant (88.5%) | n.a. | Intent-to-treat SR: 2yr: 68%; 5yr: 53% | Post-transplant, recurrence-free survival rates: 2yr: 78%; 5yr: 65% |
McMasters et al., 1997 [31] | 91 (40) | CCA | Chemoradiation (5-FU 300 mg/m2 per day), EBRT (1.8 Gy/day to a total dose of 50.4 Gy (n = 5) or 45 Gy (n = 2)), resection (9) | Resection (31)/palliative (51) | pCR: 3 chemoradiation: 100% margin-negative. No chemoradiation: 54% margin-negative. | n.r. |
Loveday et al., 2018 [32] | 43 | eCCA | Chemoradiation (55–75 Gy in 1.5 Gy BID in 4–5 weeks with 800 mg/m2 Cap), staging, maintenance chemotherapy (GEMCIS 1000 mg/m2 and 25 mg.m2 days 1/8), transplantation | n.a. | OS: 16.4. 1yrSR: 70.6%. 2yrSR: 35.3%. Post-transplant: 1yrSR: 83.3% 2yrSR: 55.6%. | PFS: 11.5 |
Welling et al., 2014 [33] | 17 | eCCA | SBRT: 50–60 Gy in 3–5 fractions in 2 weeks. 1 week after capecitabine: 1330 mg/m2/day until transplant. | n.a. | 1yrSR: 83% | n.r. |
Sarwar et al., 2021 [34] | 37 | iCCA | SIRT: Median 155 Gy (120–200 Gy) | n.a. | OS: 22 1yrOS: 60%; 2yrOS: 40% | PFS: 5.4 |
Ito et al., 2022 [35] | 19 (30) | hCCA, iCCA | 5-FU, Cap, or Gem with oxaliplatin, leucovorin, and Cis, RT, TACE, or RFA were used for some patients. Current protocol: iCCA <6 cm or hCCA and iCCA ≥6cm are treated with SBRT of 40 Gy in 5 fractions and TACE. GEMCIS for neoadjuvant chemotherapy (NAC) until LT. | Neoadjuvant CTX, neoadjuvant LT, combination | Combination: 5yr OS: 88% (hCCA), 100%(iCCA). Not combination: 5yr OS: 9% (hCCA), 41% (iCCA). | n.r. |
Hong et al., 2011 [36] | 20, (37) | hCCA, iCCA | CTX or CRT was given before and/or after surgery. 5-FU or Cap with oxaliplatin, leucovorin calcium, and gemcitabine hydrochloride was used for adjuvant and neoadjuvant protocols. | Transplant (38), partial hepatectomy (19) | Transplant: 47% (neoadjuvant and adjuvant), 20% (no therapy), 33% (adjuvant therapy). 5yr OS: 34% (iCCA), 29% (hCCA). | 5yr recurrence-free survival: 33% (transplant), 0% (partial hepatectomy). |
Author, Year | n | Site | Treatment | Comparison | Median OS (Months or %) | Median PFS (Months or %) |
---|---|---|---|---|---|---|
Ben-Josef et al., 2015 [37] | 79 | CCA, GB | After resection, 4 cycles of Gem (1000 mg/m2 days 1, 8), Cap (1500 mg/m2 days 1–14) every 21 days, then concurrent Cap (1330 mg/m2/day) and RT (45 Gy to lymphatics; 54–59.4 Gy to tumor bed) | n.a. | 2 yr SR: 65%; 67% and 60% in R0 and R1. OS: 35 (R0, 34; R1, 35). Local, distant, and combined relapse in 14, 24, and 9 patients. | n.r. |
Hughes et al., 2007 [38] | 34 | CCA | PD, chemoradiation (median dose was 50.4 Gy (40–54 Gy)). Concurrent 5-FU, followed by maintenance chemotherapy | n.a. | OS: 36.9. 5 yr SR: 35%; 5yrSR: 100% (LN-), 24% (LN+); 5 yr LC: 70%. SR: 36.9 (PD alone), 22 (PD+adjuvant therapy). | n.r. |
Hoehn et al., 2015 [39] | 8741 | CCA | Surgery, adjuvant chemotherapy; surgery alone | Surgery, adjuvant chemoradiation | MST: 24.84, 33.6, 33.12 | n.r. |
Ben-David et al., 2006 [40] | 81 | eCCA | Adjuvant EBRT: median 58.4 Gy (23–88.2 Gy) (2Gy/fraction), 54% concurrent chemotherapy | n.a. | OS: 14.7 | PFS: 11 |
Shridhar et al., 2022 [41] | 1478 | eCCA | Various RT after adjuvant chemotherapy: 25–33 fractions, 45–59.4 Gy | Adjuvant chemotherapy | RT: OS: 34, 5yrOS: 33%. No RT: OS: 27, 5yrOS: 24%. | n.r. |
Cameron et al., 1990 [42] | 96 | CCA | Surgery, RT (66%) | Stenting, RT (66%) | 1, 3, 5, 10yr SR (entire group) 49%, 12%, 5%, 2%. 1, 3, 5, 10yr SR (resected group): 66%, 21%, 8%, 4%. 1, 3, 5yr SR (stented group): 27%, 6%, 0%. | n.r. |
Mukai et al., 2019 [43] | 32 | CCA | Surgery, adjuvant RT (median dose 50 Gy) | n.a. | 2yr OS: 72.4%. LC: 65.3%; MST: 40. | DFS: 47.7% |
Horgan et al., 2012 [44] | 6712 | BTC | Adjuvant chemotherapy or adjuvant RT (systematic review + meta-analysis) | Adjuvant chemoradiation | Non-significant improvement in OS with any therapy compared with surgery alone. CTX/CTX+RT statistically better than RT. Adjuvant therapy best in LN+ and R1 disease. | n.r. |
Shinohara et al., 2008 [27] | 3839 | iCCA | Surgery alone (25%), RT alone (10%), surgery + adjuvant RT (7%) | none (58%) | OS: 6, 7, 11, 3 | n.r. |
Author, Year | n | Site | Treatment | Median OS (Months) | Median PFS (Months) |
---|---|---|---|---|---|
Liu et al., 2019 [45] | 3 | CCA | SBRT (Cyber Knife 52 Gy/4 fractions or 55 Gy/5 fractions), PD-1 blockade (nivolumab 200 mg every 2 weeks, 15 cycles) | Patient C: CR: 11 | Pt A: PFS: 13 Pt B: PFS: 7, OS: 13 |
Zhao et al., 2021 [46] | 4 | CCA | SBRT (25–60 Gy in 5–12 fractions), anti-PD-1 antibody (Nivolumab 140–200 mg) | All cases controlled, 1 became resectable; OS: 12+ | n.r. |
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Verma, S.; Grindrod, N.; Breadner, D.; Lock, M. The Current Role of Radiation in the Management of Cholangiocarcinoma—A Narrative Review. Cancers 2024, 16, 1776. https://doi.org/10.3390/cancers16091776
Verma S, Grindrod N, Breadner D, Lock M. The Current Role of Radiation in the Management of Cholangiocarcinoma—A Narrative Review. Cancers. 2024; 16(9):1776. https://doi.org/10.3390/cancers16091776
Chicago/Turabian StyleVerma, Saurav, Natalie Grindrod, Daniel Breadner, and Michael Lock. 2024. "The Current Role of Radiation in the Management of Cholangiocarcinoma—A Narrative Review" Cancers 16, no. 9: 1776. https://doi.org/10.3390/cancers16091776
APA StyleVerma, S., Grindrod, N., Breadner, D., & Lock, M. (2024). The Current Role of Radiation in the Management of Cholangiocarcinoma—A Narrative Review. Cancers, 16(9), 1776. https://doi.org/10.3390/cancers16091776