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Curative Dose Radiotherapy and Multiagent Chemotherapy in Locally Advanced Intrahepatic Cholangiocarcinoma

Cisplatin and gemcitabine are standard frontline treatments for locally advanced intrahepatic cholangiocarcinoma (ICC). This multi-institutional cohort study investigates the efficacy of curative-dose radiotherapy and multiagent chemotherapy in improving survival outcomes for unresectable ICC. Local control rates were promising, with regional lymph node metastasis occurring in less than 10% of patients. The study highlights the benefits of combining radiotherapy and chemotherapy for better oncologic outcomes in ICC patients.

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Curative Dose Radiotherapy and Multiagent Chemotherapy in Locally Advanced Intrahepatic Cholangiocarcinoma

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  1. Curative-dose radiotherapy and multiagent chemotherapy improve survival of locally advanced intrahepatic cholangiocarcinoma: A multi-institutional cohort study Jung Ho Im1,5,Jeong Il Yu2, Tae Hyun Kim3, Tae Gyu Kim4, Jun Won Kim6, and Jinsil Seong1 1Department of Radiation Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea 2Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea 3Center for Proton Therapy, National Cancer Center, Goyang, Republic of Korea 4Department of Radiation Oncology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea 5Depratment of Radiation Oncology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea 6 Department of Radiation Oncology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

  2. Background • Cisplatin and gemcitabine are the current standard frontline CTx regimens for locally advanced unresectable ICC. - median OS: 12-16 months • RTx for unresectable ICC could improve local tumor control - 2-year local control: 93–94% • The optimal combination strategy for locally advanced unresectable ICC is yet to be defined.

  3. Purpose • This multi-institutional cohort study aimed to investigate treatment outcomes and optimal radiotherapeutic strategy in patients with locally advanced unresectable ICC.

  4. Materials and methods • Eligible criteria • patients aged ≥ 20 years with histologically confirmed adenoca • RTx for locally advanced unresectable ICC • Exclusion Criteria • patients with other concurrent malignancies • patients with distant metastases • patients treated with 2-dimensional RTx

  5. Patients Characteristics & treatment profiles (N=114) Number of patients (%) or median (range) 64 (29-83) Number of patients (%) or median (range) 7 (3-16) Variable Variable Age (years) Gender Male Female T stage T1 T2 T3 T4 N stage N0 N1 Primary tumor size (cm) Satellite intrahepatic metastasis Yes No RT modality 3DCRT IMRT Proton EQD210 Systemic chemotherapy No (Radiotherapy alone) Monotherapy Combination chemotherapy 82 (71.9) 32 (28.1) 38 (33.3) 76 (66.7) 4 (3.5) 59 (51.8) 18 (15.8) 33 (28.9) 72 (63.2) 36 (31.6) 6 (5.3) 52 (30-124) 70 (61.4) 44 (38.6) 22 (19.3) 33 (28.9) 59 (51.8)

  6. Survival outcomes Median follow-up: 36 months (range, 4–158 months) The 1-year, 2-year, and 3-year LC rates were 78%, 59%, and 54%. The 1-year, 2-year, and 3-year OS rates were 64%, 39%, and 26%. • • •

  7. Patterns of failure  93 patients (82%) experienced disease recurrence. – In-field failure: 39 patients (34%) – Out-field failure: 42 patients(37%) – Distant metastases: 38 patients(33%)  Regional disease recurrence – cN0 patients (N=70): 3 patients(4.3%) – cN1 patients (N=44): 4 patients(9.1%)

  8. Prognostic factors related to LC Univariate p-value 0.714 Multivariate Number of patients (%) Variable 1-year LC (%) HR (95% CI) p-value - Age (years) < 65 ≥65 Gender Male Female T stage T1-3 T4 N stage N0 N1 Satellite intrahepatic metastasis Yes No EQD210 < 60 Gy ≥ 60 Gy Combination chemotherapy Yes No 59 (51.8) 55 (48.2) 73.4 74.0 0.846 - 82 (71.9) 32 (28.1) 75.8 70.8 0.669 - 81 (71.1) 33 (28.9) 76.4 67.9 0.508 - 70 (61.4) 44 (38.6) 75.2 72.4 0.002 2.865 (1.473-5.572) 0.002 38 (33.3) 76 (66.7) 48.7 83.8 0.001 0.312 (0.107-0.907) 0.032 85 (74.6) 29 (25.4) 65.5 95.8 0.006 0.464 (0.234-0.919) 0.028 59 (51.8) 55 (48.2) 85.3 61.2

  9. Prognostic factors related to OS Univariate p-value 0.240 Multivariate Number of patients (%) Variable 1-year OS (%) HR (95% CI) p-value - Age (years) < 65 ≥65 Gender Male Female T stage T1-3 T4 N stage N0 N1 Satellite intrahepatic metastasis Yes No EQD210 < 60 Gy ≥ 60 Gy Combination chemotherapy Yes No 59 (51.8) 55 (48.2) 60.4 67.7 0.816 - 82 (71.9) 32 (28.1) 62.6 67.2 0.101 2.096 (1.295-3.392) 0.003 81 (71.1) 33 (28.9) 66.4 57.3 0.451 1.484 (0.933-2.361) 0.095 70 (61.4) 44 (38.6) 67.7 57.4 < 0.001 2.722 (1.738-4.262) < 0.001 38 (33.3) 76 (66.7) 36.8 77.8 < 0.001 0.519 (0.278-0.967) 0.039 85 (74.6) 29 (25.4) 54.5 92.6 0.001 0.423 (0.258-0.694) 0.001 59 (51.8) 55 (48.2) 80.3 46.9

  10. Prognostic subgroup • Group 1: EQD210≥ 60 Gy RTx and combination CTx (N=23) • Group 2: EQD210< 60 Gy RTx and combination CTx or RTx and monotherapy (N=69) • Group 3: RTx alone (N=22)

  11. Conclusions • Curative-dose radiotherapy in combination with multiagent chemotherapy improved oncologic outcomes in patients with locally advanced ICC. • Regional LN metastasis occurred in less than 10% of patients; it may be recommended for primary tumors and metastatic LN in the RTx volume, excluding elective regional LN.

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