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Neoadjuvant Hypofractionated Stereotactic Body Radiation Therapy Prior to Surgery for Hepatocellular Carcinoma: a Feasibility Study.

Phase 1
Conditions
Hepatocellular Carcinoma
Interventions
Combination Product: Surgery with Neoadjuvant stereotactic body radiation therapy
Registration Number
NCT04587739
Lead Sponsor
University Hospital, Lille
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
30
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Experimental groupSurgery with Neoadjuvant stereotactic body radiation therapy-
Primary Outcome Measures
NameTimeMethod
Drop-out rateFive 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 Outcome Measures
NameTimeMethod
Duration of surgery.Postoperative 90 days
Volume of intraoperative blood lossPostoperative 90 days
Quality of life by EORTC QLQ-C30between before and after stereotactic radiotherapy
Intraoperative adverse eventsPostoperative 90 days
Postoperative severe and overall morbidity ratePostoperative 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
Toxicity of radiation therapy using the National Cancer Institute CTCAE v.5.0 criteriaPostoperative 90 days

Trial Locations

Locations (1)

Hop Claude Huriez Chu Lille

🇫🇷

Lille, France

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