Hepatocellular Carcinoma
Conditions
Keywords
Hepatocellular carcinoma, Stereotactic body radiation therapy, Hepatectomy, Neoadjuvant therapy, Drop-out
Brief summary
Hepatocellular carcinoma (HCC) is the fifth more common cancer in the world, with high mortality rates, due to the low number of patients who are eligible for therapy with curative intent, like surgical resection. Moreover, surgical resection is associated with a high risk of tumor recurrence, because of the tumor seeding through microscopic intrahepatic vessels that surround the tumor, the so-called microvascular invasion. To adequately deal with this phenomenon, the surgeon has to perform either an 'anatomical' liver resection, which remove not only the tumor but also the whole corresponding vascular network, or a 'tumorectomy' with resection margins of at least 2 cm. Unfortunately, these principles cannot always be achieved due to underlying liver cirrhosis that is present in more than 80% of patients. Stereotactic body radiation therapy (SBRT) has been proven to efficiently necrotize or stabilize HCC nodules when surgery is not possible. Our hypothesis is that pre-treatment with SBRT prior to surgical resection of HCC might improve the results through the destruction of possible seeding in the peritumoral environment. Given the novelty of this therapeutic strategy, it is necessary to verify its feasibility and safety, prior to test its efficacy in patients with HCC. The KARCHeR-1 study aims at making sure that preoperative SBRT would not result in important delays or serious adverse events such as to cancel the planned surgical resection, in patients who otherwise could have benefited from it. This issue is commonly called 'drop-out'. Thirty patients are expected to be included in the KARCHeR-1 study, which would be in favor of continuing to evaluate this therapeutic strategy if less than 3 drop-outs occur, and would be immediately discontinued if 3 drop-outs occur. Other outcomes will also been studied, like intraoperative issues, postoperative morbi-mortality, pathological features on the surgical specimen and its correlation with preoperative imaging, and finally, tumor recurrence and survival.
Interventions
COMBINATION_PRODUCTSurgery with Neoadjuvant stereotactic body radiation therapy
Stereotactic hypofractionated robotic radiation therapy (24-45 Gy / 3 fractions) followed after 4-6 weeks by conventional hepatectomy (either anatomical liver resection, or non-anatomical liver resection with intention to achieve a minimal 2 cm margin).
Sponsors
Ministry of Health, France
University Hospital, Lille
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Biopsy-proven hepatocellular carcinoma or EASL/AASLD criteria * Single nodule, 3 to 8 cm of largest diameter * Hepatocellular carcinoma eligible for conventional liver resection with curative intent (R0), without preoperative portal vein embolization
Exclusion criteria
* Performance status \> 2 * Severe comorbidity with contraindication for either surgery or radiation therapy * Decompensated liver cirrhosis (Child-Pugh B or C) * Neoplastic portal vein thrombosis or extra-hepatic metastases * Previous anticancer therapy within the last 5 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Drop-out rate | Five months after the inclusion of the last participating patient | Drop-out rate: proportion of patients in whom surgical resection cannot be achieved, due to (at least one of the following reasons): * serious adverse events related to radiation therapy (especially liver decompensation); * disease progression while receiving radiation therapy or awaiting surgery; * patient's death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of surgery. | Postoperative 90 days | — |
| Volume of intraoperative blood loss | Postoperative 90 days | — |
| Quality of life by EORTC QLQ-C30 | between before and after stereotactic radiotherapy | — |
| Intraoperative adverse events | Postoperative 90 days | — |
| Toxicity of radiation therapy using the National Cancer Institute CTCAE v.5.0 criteria | Postoperative 90 days | — |
| Postoperative severe and overall morbidity rate | Postoperative 90 days | defined using the Comprehensive Complication Index and graded with the Dindo-Clavien score |
| Postoperative mortality rate. | Postoperative 90 days | — |
| Correlation between radiological observations on preoperative imaging and pathological features on surgical specimen (like percentage of tumor necrosis). | Postoperative day 30. | — |
| Actuarial overall survival and disease-free survival. | Postoperative 24 months | — |
| Intraoperative number of packed red blood cells transfused (if any). | Postoperative 90 days | — |
Countries
France
Contacts
Primary ContactEmmanuel Boleslawski, MD,PhD
Outcome results
None listed