Abstract
BackgroundProton-beam radiotherapy (PBT) has been shown to be effective to hepatocellular carcinoma (HCC) as a nonsurgical local treatment option. However, HCC still remains as one of the most difficult cancers to be cured because of frequent recurrences. Thus, methods to inhibit the recurrence need to be explored. To prevent the HCC recurrence, we here report on a prospective phase I study of ‘in situ’ tumor vaccination using CalTUMP, a newly developed immunoadjuvant consisting of BCG extract bound to hydroxyapatite and microparticulated tuberculin, following local PBT for HCC.MethodsPatients with locally advanced recurrent HCC, which had been heavily pretreated with various treatments, were enrolled. PBT was performed with the conventional method to the target HCC. Subsequently, CalTUMP was injected into the same irradiated-tumor three times at one-week intervals. Three dose-levels of CalTUMP (1/10, 1/3, and 1/1) were administered to 3 patients each. Vital signs, blood samples, ultrasound, and computed tomographic scans were monitored to evaluate the safety.ResultsThree intratumoral injections of CalTUMP following PBT (median dose: 72.6 GyE) were accomplished in 9 patients. Transient low-grade fever and minor laboratory changes were observed in 7 patients after CalTUMP injections. No other treatment-related adverse events were observed. Median progression-free survival was 6.0 months (range: 2.1-14.2) and 4 patients were progression-free for more than 1 year.ConclusionsIntratumoral injection of CalTUMP following PBT was feasible and safe in patients with heavily pre-treated HCC. Further clinical studies to evaluate the efficacy of this in situ tumor vaccination are warranted.
Highlights
Proton-beam radiotherapy (PBT) has been shown to be effective to hepatocellular carcinoma (HCC) as a nonsurgical local treatment option
In Japan where approximately 75% of HCC are caused by hepatitis C virus infected during 1950′ to 80′, many HCC patients are aged more than 75 years old and have limited treatment options or often cannot receive treatments recommended by the guidelines
We have previously reported on a phase II randomized clinical trial in which we demonstrated that autologous formalin-fixed tumor vaccine (AFTV) made from resected tumor tissue significantly improved both overall and event-free survivals after surgery [27]
Summary
Proton-beam radiotherapy (PBT) has been shown to be effective to hepatocellular carcinoma (HCC) as a nonsurgical local treatment option. Unlike conventional X-ray, forms a unique Bragg peak ionization that enables ‘tumor-targeted irradiation’ [8] Based on this unique property, we have introduced proton beam therapy (PBT) for HCC since 1983, in collaboration with the High Energy Accelerator Research Organization at Tsukuba, and demonstrated the first evidence of curative yet safe radiotherapy for HCC [9]. We opened an in-house PBT facility at Tsukuba University Hospital in 2001, and could demonstrate its excellent local tumor control rate (83%) and further improved 5-year survival rate (44.6%) in HCC patients [12]. The recent increase of PBT facilities worldwide may indicate that more HCC patients, especially elderly patients or those with complications, will be treated by PBT in the near future
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