Abstract
PurposeTo assess feasibility and safety of conventionally fractionated radiotherapy (cfRT) in patients with hepatocellular carcinoma (HCC).MethodsPatients 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.ResultsThe 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.ConclusionConventionally 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 registrationClinicalTrials.gov identifier NCT00777894, registered October 21st, 2008.
Highlights
Hepatocellular carcinoma is the most common primary liver tumor and the 2nd leading cause of cancer related mortality worldwide
The Lyman normal tissue complication probability (NTCP) model and a local damage-organ injury NTCP model later have been used to describe the partial tolerance of the liver to RT [6]
We report the results of the Swiss Group for Clinical Cancer Research (SAKK) 77/07 phase I trial assessing feasibility and safety of conventionally fractionated radiotherapy (cfRT) in patients with locally advanced non-resectable hepatocellular carcinoma (HCC)
Summary
Hepatocellular carcinoma is the most common primary liver tumor and the 2nd leading cause of cancer related mortality worldwide. It represents 7% of all diagnosed cancers and its overall 5-year survival rate < 12%. Dose escalation to the diseased liver segments has become possible This trial was conducted to obtain better understanding of the RT dose-response-relationship for tumor control as well as for normal tissue toxicities in this patient group. We report the results of the Swiss Group for Clinical Cancer Research (SAKK) 77/07 phase I trial assessing feasibility and safety of cfRT in patients with locally advanced non-resectable HCC
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