Background and Rationale

Hepatocellular carcinomas (HCC) have traditionally been cancers with dismal prognoses and limited options for treatment. Only a small proportion of patients are eligible for receiving curative treatments such as resection or liver transplant while the majority of patients are deemed ineligible for curative treatments due to advanced stage of disease or poor liver function.  Patients with such advanced tumours are then treated with a number of other modalities including minimally invasive locally ablative therapies such as radiofrequency ablation, microwave ablation, percutaneous ethanol injection, trans-arterial bland embolization, trans-arterial chemo-embolization (TACE) or trans-arterial radioembolization (TARE) and non-invasive ablative therapies such as stereotactic radiotherapy or proton beam therapy. Similarly, the use of radiation therapy, both SBRT and proton therapy, has been described in the case of unresectable intrahepatic cholangiocarcinoma (ICC). Proton beam therapy (PBT) for the treatment of HCC and ICC has been reported from several institutions in Japan, Korea and USA.  These studies showed encouraging outcomes in terms of response to therapy and side effect profile, even for large tumours, tumours with portal vein involvement and in patients with poor liver function at baseline. On the basis of the early Phase I and Phase II studies, currently a randomized controlled trial is ongoing in the USA comparing protons and photon-based radiotherapy in unresectable hepatocellular carcinomas. As the only proton centre in South Asia and the Middle East, Apollo Proton Cancer Centre (APCC) is in a unique situation to prospectively follow up all patients with liver tumours undergoing proton beam therapy at this centre to monitor their outcomes.

General aim

To determine clinical outcomes (toxicity, local control, overall survival, and patterns of recurrence) in patients with, non-metastatic primary liver tumours treated with pencil-beam scanning proton beam therapy.

Primary objective(endpoint)

To report the proportion of patients developing decline in liver function at 1 and 3 months after proton therapy and the patient, tumour and treatment factors influencing this.

Secondary objectives(endpoints)             

- Time to progression of the treated lesion and factors affecting these.

-Local control rates of lesions undergoing proton therapy and the patient, tumour and treatment characteristics influencing this.

-Overall survival and progression-free survival of all patients.

-Acute and late toxicity according to CTCAE v5.0.

-Quality of life for all patients using EORTC-QLQ-C30 and EORTC-QLQ-HCC18  or  EORTC-QLQ-BIL21at completion of treatment and at 1, 3, 6 & 12 months after treatment completion.

Design 

Observational Prospective

Population

All patients with primary liver tumors (hepatocellular cancer or intrahepatic cholangiocarcinomas) treated with proton therapy at the Apollo Proton Cancer Centre who consent to the study.

Statistical considerations

Descriptive statistical analysis will be applied to routine demographic data collected, expressed as frequency for categorical variables. Chi-square test and Fisher’s exact test will be used for comparisons. Kaplan Meier curves will be used to summarize the time to event endpoints over time. Log-rank test will be used to test for differences in dichotomous variables in the time-to-event analysis. Factors significant in the univariate analysis will be tested by multivariate analysis using the Cox proportional hazard model.