HERCOLES2: Hepatocarcinoma Recurrence on the Liver Study - Part2

Sponsor

University of Milano Bicocca (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04053231

Collaborator

(none)

3,000

Enrollment

Locations

176

Anticipated Duration (Months)

157.9

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Rationale for the trial. To evaluate the impact of surgery on hepatocarcinoma recurrence. Thus, to evaluate the impact of different clinical, radiological, histopathological variables on recurrence after surgical treatment. The nature of this study will allow to observe, over time, the distribution of the considered collection variables, allowing a strictly observational monitoring of possible associations able to suggest models or interpretations, which can then be the basis for the construction of prospective and randomized studies.

Condition or Disease	Intervention/Treatment	Phase
Liver Cancer Surgery Recurrence Tumor Cirrhosis	Other: liver resection

Detailed Description

Hepatocellular carcinoma (HCC) is 1 of the 5 most common malignancies worldwide and the third most common cause of cancer related mortality of 500,000 deaths globally every year. Although more common in East Asia, the incidence of HCC is increasing in the Western world. Hepatic resection is the first-line therapeutic option and it is accepted as a safe treatment with a proven impact on prognosis, with a low operative mortality as the result of advances in surgical techniques and perioperative management. Nevertheless, surgical resection is applicable in only about 20% to 30% of patients with HCC, since most have poor hepatic reserve function caused by underlying chronic liver disease and multifocal hepatic distributions of HCC.

Although hepatic resection is one of the curative treatments for hepatocellular carcinoma, the recurrence rate of HCC even after curative resection is quite high, estimated to be approximately 50 % during the first 3 years and more than 70 % during the first 5 years after curative resection, and so the postoperative long term results remain unsatisfactory. In this scenario the role of liver transplantation has been, in the last years, predominant, due to the ability of transplant to reduce disease recurrence, because of the treatment of liver cirrhosis associate to HCC which represent the most important driver to recurrence. Otherwise the scarcity of organ source has been a boost to the spread of liver resection, not only confined in the boundary taken into account in the BCLC algorithm (guidelines endorsed by EASL and AASLD), but even in patients considered not suitable for curative treatment as well as liver resection.

Although surgical treatment has been adopted in the last years in more patients outside the Guidelines with satisfactory results in term of mortality, morbidity and Short term oncological outcomes, the limits of this approach remain the long term disease free survival.

Risk factor for recurrence has been yet identified in the last years as hcc dimension, grading, microvascular invasion and satellitosis. The evidence that these two prognostic factors could negatively impact on the long term prognosis enhancing the risk of recurrence, has led many Author to propose anatomical resection (segmental resection) as the ideal surgical treatment to reduce these risks in HCC patients. Otherwise literature results are in conflict regarding the real benefit of this approach. In fact in many patients with HCC and underlying cirrhosis the anatomical approach is not feasible due to the risk of postoperative liver failure. So a parenchyma-sparing technique has been developed and compared to anatomical resection in term of oncological outcomes. Even if radiological and clinical pictures seems to predict the prognosis of resected HCC, the pathophysiology behind the recurrence is still unclear.Currently, data suggests two type of recurrence presentation: intrahepatic metastasization (IM) and multicentric occurrence (MO) of de novo HCC based on the precancerous status of the remnant diseased liver. Several effort has been done to preoperatively identified the 2 pattern of recurrences. Genetical studied has been performed, especially in eastern countries to better clarify and understand the impact of the 2 phenomena. In the japanese guidelines are described histo-pathological hallmarks able, in retrospect, to define the type of recurrence, metastases or de novo tumor. Moreover, several recent studies including a metanalysis, seems to show that de novo recurrence could have a better prognosis when approached surgically, with a significant improvement in overall and disease-free survival rates. The model of HCC recurrence is not yet well clarified as well as the best treatment of hcc recurrence. On these data is based the proposal to create an Italian study project on surgical treatment and surgical outcomes of hepatocellular carcinoma in term of disease free survival. The idea growth up from the finding that, although the curative intent of surgical approach, results are not so satisfactory and it seems to not ameliorate the long term patient's prognosis and long term disease-free outcome without the need for therapies, conditioning the real everyday life of patient. In Italy is not yet present a study group that draw together the experience of surgical centers with low,medium or high volume of surgical procedures on HCC, with the intent to offer radical cure through surgery as the first choice treatment. The intent is to collect Big Data through a common database, with high power of analysis and high scientific impact, to better understand the mechanism which regulate HCC recurrence and to identify the best clinical treatment option for these patients.

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

3000 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Hepatocarcinoma Recurrence on the Liver Study - Part2

Anticipated Study Start Date :

Sep 1, 2019

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

May 1, 2034

Outcome Measures

Primary Outcome Measures

Disease-free-Survival [15 years of follow-up]
Disease Free Survival: the time between surgery and event of recurrence or death measured in months. If no event, patients will be censored at the last available follow-up date.
Overall Survival [15 years of follow-up]
The time from surgery to death measured in months. If no event, patients will be censored at the last available follow-up.

Secondary Outcome Measures

Localization of the recurrence [15 years of follow-up]
Presence of relapse disease on the surgical cut surface rather than at distance
Number of redo-surgery [15 years]
Number of patients who experienced a recurrence after first surgery and has been submitted to a redo-surgery procedure

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

No age limit.
Hepatocarcinoma diagnosis confirmed at histological specimen
Every single patients with first HCC diagnosis or with a recurrence/persistence disease evaluated and treated with surgery at the participating center.
the assessment for patient enrollment must have been performed starting from 02/02/2019.

Exclusion Criteria:

Surgery as a downstaging therapy for transplant
Patients treated with surgery in case of not-curative intent (palliation, best supportive care, etc).
Histopathological specimen of combined liver primary neoplasms (e.g. "hepatocholangiocarcinoma'').
Patients with other tumors in the previous past.

Contacts and Locations

Locations

	Site	City	Country
1	Chirurgia Rubino - Policlinico di Bari	Bari	Italy
2	Ospedale Maggiore- AUSL	Bologna	Italy
3	Chirurgia Generale Bolzano	Bolzano	Italy
4	Fondazione Poliambulanza - Istituto Ospedaliero	Brescia	Italy
5	Spedali Civili	Brescia	Italy
6	Chirurgia Generale Ospedale Pierantoni - Morgagni	Forlì	Italy
7	Ospedale A. Manzoni - ASST Lecco	Lecco	Italy
8	ASST-Mantova	Mantova	Italy
9	Asst-Fbf-Sacco Polo Universitario H. Sacco Chirurgia 2	Milan	Italy
10	IRCCS Osp. San Raffaele, Divisione Chirurgia Generale Epatobiliare	Milan	Italy
11	Policlinico di Monza	Monza	Italy
12	UOS Chirurgia Oncologica ad inidirzzo epato-bilio-pancreatico	Parma	Italy
13	Fondazione IRCCS Policlinico San Matteo	Pavia	Italy
14	Fondazione Policlinico Universitario A. Gemelli, IRCCS	Rome	Italy
15	Irccs Istituto Nazionale Tumori Regina Elena	Rome	Italy
16	Humanitas Research Hospital	Rozzano	Italy
17	Ospedale San Paolo	Savona	Italy
18	Chirurgia 4 Ospedale Ca'Foncello	Treviso	Italy
19	Chirurgia Epatobiliare Università degli studi di Verona	Verona	Italy