None listed
Conditions
Brief summary
The primary purpose of this trial is to assess the safety and efficacy of stereotactic ablative body radiotherapy (SABR) for liver cancer which has re-occurred or not responded to radiology treatment (TACE). Who is it for? You may be eligible to participate in this trial if you are aged 18 or over and have been diagnosed with hepatocellular carcinoma (liver cancer), which has been pre-treated with TACE with incomplete response or re-occurrence, and is deemed suitable for SABR therapy by your treating clinicians. Study details All participants enrolled in this trial will receive SABR therapy. The treating team of clinicians may determine that it would be useful to insert fiducial markers in some participants, which are small gold markers, inserted around the tumour to act as a reference point across different images. Within 5 days of fiducial marker insertion (where applicable), all participants will undergo a CT scan simulating the body immobilisation procedure. This will take approximately 45 minutes to one hour. A full body immobilisation system is utilised to create an impression of the body. The CT scan is more in depth than a regular CT and takes multiple images. Small tattoos are drawn onto the patient to act as a guide to allow the lasers to line up during treatment. In order to help the patient stay still and breathe regularly, they are asked to breathe in time with a metronome (typically 30 bpm). Participants will then undergo three SABR treatment sessions over the next two to three weeks, which involves delivery of radiotherapy to the tumour. The treatment takes approximately one hour and consists of using the full body immobilisation system and the tattoo guides to ensure the patient is in the correct position and alignment for the precise delivery of radiation to the tumour. A quick scan is then done to check the positioning, followed by a more in depth CT scan to verify this. When the treating team are happy with the positioning, the treatment radiation dose will be delivered, followed by a pause mid treatment to verify and confirm the positioning once again. Post treatment all participants will be followed up every few months for up to 24 months following completion of SABR treatment. This will involve blood tests, CT/MRI scans to assess tumour progression, and monitoring of the side effects related to SABR treatment. It is hoped that the findings from this trial will provide information on whether SABR, with or without fiducial maker insertion, is safe and effective for the treatment of liver cancer, where the tumours have not responded or re-occurred following treatment with TACE.
Interventions
Imaging of patients will be reviewed by investigating EUS Endoscopist and Radiation Oncologist. If required, radiotherapy fiducial markers will be placed by EUS in four quadrants of the ablated site, or surgical margin to outline its peripheral borders. EUS and fiducial placement will be carried out in accordance with Gastroenterology and Hepatology Unit protocol at the Royal Adelaide Hospital. Fiducial insertion will be performed by A/Prof Nam Quoc Nguyen MBBS (Hons) PhD FRACP, Consultant Gastr
Imaging of patients will be reviewed by investigating EUS Endoscopist and Radiation Oncologist. If required, radiotherapy fiducial markers will be placed by EUS in four quadrants of the ablated site, or surgical margin to outline its peripheral borders. EUS and fiducial placement will be carried out in accordance with Gastroenterology and Hepatology Unit protocol at the Royal Adelaide Hospital. Fiducial insertion will be performed by A/Prof Nam Quoc Nguyen MBBS (Hons) PhD FRACP, Consultant Gastroenterologist/ Interventional Endoscopist at the Royal Adelaide Hospital. The patient is sedated for the procedure which takes approximately 15 minutes to complete. CT simulation will be performed within five days after fiducial placement. Simulation will employ full body immobilization (Omni V SBRT system), multi-detector 4DCT with 3mm slices and IV contrast (late arterial phase scan). Simulation tumour motion study will be assessed to determine the degree of tumour excursion. Treatment planning is determined by imaging (CT or MRI) to ensure accurate delineation of the target volume on the 4DCT maximum intensity projection. SABR will be scheduled to commence within two weeks from simulation. The planning criteria will be as follows: Planning Target Volumes (PTV): In ablated lesions, PTV will be determined by gross tumour volume (GTV) plus uniform 5mm margin. In resected lesions, PTV will be determined by the clinical target volume (CTV) plus uniform 5mm margin. The absorbed dose will be 42-45Gy in three fractions to each PTV (BED10 = 100.8Gy). The prescription isodose should encompass at least 95% of the PTV. The maximum dose within the PTV should not exceed 140%. Treatment delivery will be in three fractions, with a maximum of two fractions per week at least 48 hours apart. Online image matching process of the gold seed fiducial markers to the reference image will be carried out. Follow up: The clinical outcomes of tumour size, AFP and survival will be collected at 1, 3, 6, 9, 12, 18 and 24 months after the completion of treatment. The exact modality of radiological restaging (CT or MRI) will be at the discretion of the HCC MDT, to allow for the best method of assessing efficacy of therapy. Any subsequent therapy due to progression of HCC (if needed), will be determined by the HCC MDT. To evaluate the feasibility and safety of fiducial marker insertion and SABR on liver disease evident by decompensation of synthetic liver dysfunction or regional toxicity from radiation - weekly blood tests (CBP, EUC, LFT and INR) will be performed from commencement and up to four weeks after completion of SABR, to assess for deterioration of liver impairment/failure. Side effect profile will be carefully documented including any pain, discomfort, nausea or vomiting during or post SABR. Complications related to EUS insertion of fiducials will be recorded, including fiducial migration, bleeding, and organ perforation. Fiducial markers: endoscopic ultrasound guided insertion of 3 gold markers in the peritumoural region. SABR: ct simulation takes approximately 45 min to 1 hour. SABR is delivered over 3 fractions at least 48 hours apart. Each fraction takes approximately 30-45 min to complete. The decision for 42 vs 45Gy is determined at the time of radiotherapy planning. Where the dose can be delivered safely without exceeding the normal tissue constraints, 45Gy in 3 fractions would be choice at the discretion of the radiation oncologist. The timing is a departmental logistical decision. Whilst adhering to the rule of 48 hrs apart and 2 fractions max per week, the logistical capacity of the department to treat is the determining factor regarding exact timing. Exact isodose is determined at planning – this choice is a balance of achieving dose coverage of the tumour target and maintaining a dose max that is within the recommended constraints.
Sponsors
Royal Adelaide Hospital
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
INCLUSION CRITERIA Aged > 18 years Able to give informed consent ECOG 0-1 Barcelona clinic liver cancer (BCLC) class A/B as determined by a Hepatocellular Carcinoma Multidisciplinary team (HCC MDT) HCC diagnosed by standard radiological criteria or histology HCC < 6cm which is amenable to SABR Pre-treated with TACE with incomplete response or re-occurrence Measureable disease on imaging defined by M RECIST criteria
Exclusion criteria
EXCLUSION CRITERIA BCLC C (significant decompensated liver disease or HCC not amenable to TACE) Significant comorbidities unable to safely tolerate sedation/anaesthetic Expected life expectancy of < 24 months Prior radiotherapy to abdomen Pregnant or lactating (any woman of childbearing potential must have a pregnancy test prior to enrollment and must take adequate precautions to prevent pregnancy during treatment)
Outcome results
None listed