Journal article
External beam radiotherapy for unresectable hepatocellular carcinoma, an international multicenter phase I trial, SAKK 77/07 and SASL 26.
- Herrmann E Department of Radiation Oncology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland. evelyn.herrmann@bluewin.ch.
- Naehrig D Division of Radiation Oncology, Basel University Hospital, Basel, Switzerland.
- Sassowsky M Department of Radiation Oncology and Division of Medical Radiation Physics, Bern University Hospital, Bern, Switzerland.
- Bigler M SAKK Coordinating Center, Bern, Switzerland.
- Buijsen J Department of Radiation Oncology (MAASTRO Clinic), GROW - School for Oncology and Developmental Biolog, Maastricht, The Netherlands.
- Ciernik I Department of Radiation Oncology, University of Zurich, Zurich, Switzerland.
- Zwahlen D Department of Radiation Oncology, Hospital Graubuenden, Chur, Switzerland.
- Pellanda AF Radiation Oncology Department, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
- Meister A Centre for Radiation Oncology, KSA-KSB, Kantonsspital Aarau, Aarau, Switzerland.
- Brauchli P SAKK Coordinating Center, Bern, Switzerland.
- Berardi S Department of Radiation Oncology and Division of Medical Radiation Physics, Bern University Hospital, Bern, Switzerland.
- Kuettel E SAKK Coordinating Center, Bern, Switzerland.
- Dufour JF Department of Hepatology, University Clinic of Visceral Surgery and Medicine, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland.
- Aebersold DM Department of Radiation Oncology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland.
- 2017-01-15
Published in:
- Radiation oncology (London, England). - 2017
Conformal radiotherapy
Hepatocellular carcinoma
Liver
Radiation toxicity
Aged
Aged, 80 and over
Carcinoma, Hepatocellular
Female
Humans
Liver Neoplasms
Male
Maximum Tolerated Dose
Middle Aged
Radiotherapy Dosage
Radiotherapy, Conformal
English
PURPOSE
To assess feasibility and safety of conventionally fractionated radiotherapy (cfRT) in patients with hepatocellular carcinoma (HCC).
METHODS
Patients with histologically confirmed stage cT1-4, cN0-1 HCC and Child-Pugh Score (CPS) A or B disease were included in a phase I multicenter trial. Metastatic HCC were allowed if ≥90% of total tumor volume was located within the liver. Patients were enrolled onto five dose-escalation levels (54-70Gy in 2Gy fractions) based on a modified 3 + 3 design, with cohorts of five patients instead of three patients in dose levels 4 and 5. Primary trial endpoint was dose-limiting toxicity (DLT), as specifically defined for 17 clinical and nine laboratory parameters as grade ≥3 or ≥4 toxicity (CTCAE vs. 3). The threshold to declare a dose level as maximum tolerated dose (MTD) was defined as a DLT rate of ≤16.7% in dose levels 1-3, and ≤10% in dose levels 4-5. Best objective response of target liver lesions and adverse events (AE's) were assessed as secondary endpoints.
RESULTS
The trial was terminated early in DL 3 due to low accrual. Nineteen patients were recruited. Fifteen patients were evaluable for the primary and 18 for the secondary endpoints. Maximum tolerated dose was not reached. One patient in dose level 1, and one patient in dose level 2 experienced DLT (lipase > 5xULN, and neutrophils <500/μL respectively). However, dose level 3 (62Gy) was completed, with no DLTs in 3 patients. Overall, 56% of patients had a partial response and 28% showed stable disease according to RECIST. No signs of radiation induced liver disease (RILD). Two patients in dose level 3 experienced lymphocytopenia grade 4, with no clinical impact.
CONCLUSION
Conventionally fractionated radiotherapy of 58Gy to even large HCC was safe for patients with CPS A and B. 62Gy was delivered to three patients without any sign of clinically relevant increased toxicity. The maximum tolerated dose could not be determined.
TRIAL REGISTRATION
ClinicalTrials.gov identifier NCT00777894 , registered October 21st, 2008.
To assess feasibility and safety of conventionally fractionated radiotherapy (cfRT) in patients with hepatocellular carcinoma (HCC).
METHODS
Patients with histologically confirmed stage cT1-4, cN0-1 HCC and Child-Pugh Score (CPS) A or B disease were included in a phase I multicenter trial. Metastatic HCC were allowed if ≥90% of total tumor volume was located within the liver. Patients were enrolled onto five dose-escalation levels (54-70Gy in 2Gy fractions) based on a modified 3 + 3 design, with cohorts of five patients instead of three patients in dose levels 4 and 5. Primary trial endpoint was dose-limiting toxicity (DLT), as specifically defined for 17 clinical and nine laboratory parameters as grade ≥3 or ≥4 toxicity (CTCAE vs. 3). The threshold to declare a dose level as maximum tolerated dose (MTD) was defined as a DLT rate of ≤16.7% in dose levels 1-3, and ≤10% in dose levels 4-5. Best objective response of target liver lesions and adverse events (AE's) were assessed as secondary endpoints.
RESULTS
The trial was terminated early in DL 3 due to low accrual. Nineteen patients were recruited. Fifteen patients were evaluable for the primary and 18 for the secondary endpoints. Maximum tolerated dose was not reached. One patient in dose level 1, and one patient in dose level 2 experienced DLT (lipase > 5xULN, and neutrophils <500/μL respectively). However, dose level 3 (62Gy) was completed, with no DLTs in 3 patients. Overall, 56% of patients had a partial response and 28% showed stable disease according to RECIST. No signs of radiation induced liver disease (RILD). Two patients in dose level 3 experienced lymphocytopenia grade 4, with no clinical impact.
CONCLUSION
Conventionally fractionated radiotherapy of 58Gy to even large HCC was safe for patients with CPS A and B. 62Gy was delivered to three patients without any sign of clinically relevant increased toxicity. The maximum tolerated dose could not be determined.
TRIAL REGISTRATION
ClinicalTrials.gov identifier NCT00777894 , registered October 21st, 2008.
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.1186/s13014-016-0745-0
- PMID 28086942
- Persistent URL
- https://roar.hep-bejune.ch/global/documents/44139
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