scispace - formally typeset
Search or ask a question
Journal ArticleDOI

Patients with advanced hepatocellular carcinoma need a personalized management: A lesson from clinical practice

TL;DR: BCLC C stage does not identify patients homogeneous enough to be allocated to a single stage, and new patient‐tailored therapeutic indications are needed.
About: This article is published in Hepatology.The article was published on 2018-05-01 and is currently open access. It has received 93 citations till now.

Summary (3 min read)

Clinical Practice

  • Their aim was to assess treatment and overall survival (OS) of BCLC C patients subclassified according to clinical features (performance status [PS], macrovascular invasion [MVI], extrahepatic spread [EHS] or MVI 1 EHS) determining their allocation to this stage.
  • From the Italian Liver Cancer database, the authors analyzed 835 consecutive BCLC C patients diagnosed between 2008 and 2014.
  • The remaining patients should be subclassified according to PS and tumor features, and new patient-tailored therapeutic indications are needed.

PATIENTS

  • Data were extracted from the last version of the Italian Liver Cancer (ITA.LI.CA) database, including *These authors contributed equally to the design and conduction of the study.
  • Prof. Trevisani consults for, advises for, is on the speakers’ bureau for, and received grants from Bayer, also known as Potential conflict of interest.
  • AND REPRINT REQUESTS TO: Franco Trevisani, M.D. Department of Medical and Surgical Sciences, Semeiotica Medica Unit Alma Mater Studiorum–University of Bologna Albertoni Street n. 15 41057 Bologna, Italy E-mail: franco.trevisani@unibo.it Tel: 139 051 2142923 6,477 HCC patients consecutively evaluated and managed from January 1987 to December 2014 at 24 Italian medical centers.
  • Before statistical evaluation, the consistency and accuracy of the data set were checked by the group coordinator (F.T.), and, whenever clarification or additional information were needed, resubmitted to the generating center.
  • Therefore, patients with PS0 were included into the MVI, EHS, or MVI 1 EHS subgroups.

TREATMENT

  • Treatment distribution significantly differed among BCLC C subclasses (Table 3).
  • In PS2 patients, BSC was the most frequent therapeutic approach (41.8%), followed by curative (29.5%; mainly percutaneous ablation 24%) and transarterial (17.1%) therapies, whereas sorafenib was administered in 8.2% of these patients.
  • Expectedly, in both MVI and EHS patients, sorafenib was the most frequent treatment option (39.3% and 37.3%, respectively), whereas the majority (51.7%) of patients with MVI 1 EHS were managed with BSC.
  • In a further subanalysis that included Child-Pugh class A patients only (Supporting Fig. S1), sorafenib was the most common treatment not only in patients with either MVI (47.1%) or EHS (45.9%), but also in those with MVI 1 EHS (57.1%).

STATISTICAL ANALYSIS

  • Continuous data are shown as median and 95% confidence interval (CI) and discrete variables as absolute and relative frequencies.
  • Comparison of continuous data was carried out using the Kruskal-Wallis test, and comparison between discrete variables was carried out using the Fisher’s exact test or the v2 test with Yates’ correction, as appropriate.
  • Variables associated (P < 0.10) with survival at univariate analysis were entered into a Cox’s multivariate regression analysis.

ETHICS

  • The ITA.LI.CA database management conforms to the current Italian legislation on patient confidentiality, and this study conforms to the ethics guidelines of the Declaration of Helsinki.
  • All patients provided informed consent to having their data recorded in an anonymous way in the ITA.LI.
  • CA database and its use for cooperative studies were approved by the ethic committees/ institutional boards of participating centers.

PATIENT CHARACTERISTICS

  • Table 2 reports demographic and clinical features of BCLC C patient subclassified according to PS, and presence of MVI and/or EHS.
  • Moreover, HCC characteristics and AFP levels were significantly different among the various subclasses (P < 0.001).
  • Interestingly, median platelet count progressively increased from PS1 and PS2 patients to MVI and EHS patients, with the highest values observed in MVI 1 EHS patients (P < 0.001).

SURVIVAL ANALYSES

  • In order to assess whether the degree of vascular invasion had a prognostic impact, MVI patients were further subdivided according to the location/extension of vascular invasion, as follows: central MVI (c-MVI) if it involved the main portal trunk (n 5 86; 38.4%) and peripheral MVI (p-MVI) if only first-order or segmental portal vein branches were involved (n 5 108; 48.2%).
  • These variables were entered into a multivariate analysis.

SURVIVAL DIFFERENCES

  • In a real-world setting, such as the one described in their study, BCLC C patients showed a markedly different prognosis according to the characteristics that determined the assignment to this stage.
  • This analysis showed that patients with PS1 more frequently went through more than one line of HCC treatment as compared to the other groups, underscoring the fact that these patients are able to tolerate more than one treatment, and that this occurrence does not seem to have a negative effect on survival.
  • Nonetheless, these patients also showed a rather long survival (median, 22.3 months), which exceeded by far that of patients with MVI and/or EHS.

TREATMENT DIFFERENCES

  • A certain shift toward locoregional treatments was also observed in MVI patients, and, unexpectedly, this deviation was also observed in patients with EHS.
  • As a matter of fact, using a patient-tailored management established by a multidisciplinary expert team, the authors achieved a median survival of 22.3 months in BCLC C patients, which is remarkably longer than the one achieved with sorafenib in both randomized and postmarketing Western studies.
  • Interestingly, in the setting of advanced HCC, the authors confirmed the dismal prognostic meaning of increasing platelet count, which has been already described in unselected HCC patients.

LIMITATIONS

  • The retrospective nature of their study does not allow us to exclude unintended biases and precluded a regimented follow-up of patients and an estimation of the effect of unrecorded confounding factors, such as severity of comorbidities, local facility to access to certain treatments, and patient’s and physician’s preferences.
  • These shortcomings should be weighed in light of a multicenter large registry collecting realworld observational data generated by the clinical practice and partnership of academic and nonacademic centers.
  • Moreover, their data pertain to an European population of patients mainly infected with hepatitis C virus (HCV), and a validation in other populations with different clinical and ethnic background, and where inherent variations may exist in the provision of locoregional and systemic therapies are needed and eagerly awaited.
  • (35) This method postulates a management established by a multidisciplinary expert team and principally based on an individualized (rather than stage-based) approach in order to offer the best treatment to each patient, according to his or her own characteristics.

Did you find this useful? Give us your feedback

Citations
More filters
Journal ArticleDOI
TL;DR: The major risk factors for hepatocellular carcinoma (HCC) in contemporary clinical practice are becoming increasingly related to sustained virological response after hepatitis C, suppressed hepatitis B virus during treatment, and alcoholic and nonalcoholic fatty liver disease.

958 citations

Journal ArticleDOI
TL;DR: A critical analysis of the different conceptual approaches to HCC management is provided, highlighting their advantages and disadvantages and focusing on the remarkable differences between the stage‐guided and the hierarchical strategies.

103 citations


Cites background or methods or result from "Patients with advanced hepatocellul..."

  • ...(5,17,22) It would be relevant here to underline that, despite the extensive worldwide use of the BCLC system for the classification of patients with HCC and its repeated updating over time, numerous studies have reported poor adherence to its therapeutic indications even by the Western expert centers,(23-26) particularly in patient allocation to LR....

    [...]

  • ...In this context, for example, LR is not considered a possible therapeutic option for BCLC B and C patients despite the availability of several studies demonstrating that LR outperforms the locoregional therapies for selected patients in these BCLC stages.(15,20-29)...

    [...]

  • ...There is huge evidence in support of this precise therapeutic hierarchy irrespective of tumor stage.(15-29) For instance, the use of “treatment hierarchy” is corroborated by the fact that the first-line treatment has been proven to be an independent predictor of survival in patients belonging to intermediate or advanced BCLC stages....

    [...]

  • ...(15-29) For instance, the use of “treatment hierarchy” is corroborated by the fact that the first-line treatment has been proven to be an independent predictor of survival in patients belonging to intermediate or advanced BCLC stages.(24,26,29) In these two stages, the observed mortality was lower in patients who underwent an “upward” (right-to-left) therapeutic migration compared to those who were managed with the FIg....

    [...]

  • ...Such an evolution of HCC treatment finds support in an extensive amount of evidence, indicating that this strategy outperforms the systematic adoption of chemoembolization for BCLC B patients as well as systemic therapy for BCLC C patients with intrahepatic vascular invasion.(20-29,45-48)...

    [...]

Journal ArticleDOI
TL;DR: It is concluded that a personalised, data-driven approach to care with active management from a multidisciplinary team, as well as increased communication and collaboration between clinicians and researchers based in east and the west, could help to reduce the differences in management and optimise treatment strategies.

85 citations

Journal ArticleDOI
TL;DR: The study suggests that ETS‐1 could enhance the activation of PXR and be a potential therapeutic target for overcoming Sorafenib resistance in HCC treatment.

65 citations

References
More filters
Journal ArticleDOI
TL;DR: In patients with advanced hepatocellular carcinoma, median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo.
Abstract: Background No effective systemic therapy exists for patients with advanced hepatocellular carcinoma. A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and Raf may be effective in hepatocellular carcinoma. Methods In this multicenter, phase 3, double-blind, placebo-controlled trial, we randomly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib (at a dose of 400 mg twice daily) or placebo. Primary outcomes were overall survival and the time to symptomatic progression. Secondary outcomes included the time to radiologic progression and safety. Results At the second planned interim analysis, 321 deaths had occurred, and the study was stopped. Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group (hazard ratio in the sorafenib group, 0.69; 95% confidence interval, 0.55 to 0.87; P<0.001). There was no significant difference between the two groups in the median time to symptomatic progression (4.1 months vs. 4.9 months, respectively, P=0.77). The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group (P<0.001). Seven patients in the sorafenib group (2%) and two patients in the placebo group (1%) had a partial response; no patients had a complete response. Diarrhea, weight loss, hand-foot skin reaction, and hypophosphatemia were more frequent in the sorafenib group. Conclusions In patients with advanced hepatocellular carcinoma, median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo.

10,074 citations

Journal ArticleDOI
TL;DR: The Eastern Cooperative Oncology Group criteria for toxicity and response are presented to facilitate future reference and to encourage further standardization among those conducting clinical trials.
Abstract: STANDARD CRITERIA FOR TOXICITY and for response to treatment are important prerequisites to the conduct of cancer trials. The Eastern Cooperative Oncology Group criteria for toxicity and response are presented to facilitate future reference and to encourage further standardization among those conduc

9,661 citations


"Patients with advanced hepatocellul..." refers background or methods in this paper

  • ..., patients restricted in physically strenuous activity, but ambulatory and able to carry out a light/sedentary work((22))) does not preclude the access to all available HCC treatments....

    [...]

  • ...PS was assessed according to the Eastern Cooperative Oncology Group (ECOG).((22))...

    [...]

Journal ArticleDOI
TL;DR: Emergency ligation of bleeding oesophageal varices using the Milnes Walker technique was performed in 38 patients, and in patients with good preoperative liver function this rose to 71% and the simple scoring system for grading the severity of disturbance of liver function was found to be of value in predicting the outcome of surgery.
Abstract: Emergency ligation of bleeding oesophageal varices using the Milnes Walker technique was performed in 38 patients. Haemorrhage continued or recurred in hospital in 11 patients, all of whom subsequently died. A further 10 patients died in hospital following operation from hepatic failure and a variety of other causes. Five patients were finally considered suitable for elective shunt surgery, but of 12 patients who were discharged without a further operation, only 2 have re-bled. Although the overall 6-month survival was 32 per cent, in patients with good preoperative liver function this rose to 71 per cent, and the simple scoring system for grading the severity of disturbance of liver function was found to be of value in predicting the outcome of surgery. Since the results of emergency ligation of bleeding oesophageal varices in our hands have been so disappointing we are currently using it less and are trying the mesenteric caval jump graft as an emergency operation for the control of bleeding varices.

7,262 citations


"Patients with advanced hepatocellul..." refers methods in this paper

  • ...Child-Pugh score((25)) was categorized as A, B 7 (threshold for eligibility to TACE), and B 8-9, and the size of HCC (largest lesion of multinodular tumours) was categorized as 2, 2....

    [...]

Journal ArticleDOI
TL;DR: The American Association for the Study of Liver Diseases (AASLD) practice guidelines on the management of hepatocellular carcinoma (HCC) were updated in 2010 as discussed by the authors.

6,964 citations

01 Jan 2010
TL;DR: Since the publication of the American Association for the Study of Liver Diseases (AASLD) practice guidelines on the management of hepatocellular carcinoma (HCC) in 2005, new information has emerged that requires that the guidelines be updated.
Abstract: Since the publication of the American Association for the Study of Liver Diseases (AASLD) practice guidelines on the management of hepatocellular carcinoma (HCC) in 2005, new information has emerged that requires that the guidelines be updated. The full version of the new guidelines is available on the AASLD Web site at http://www.aasld.org/practiceguidelines/ Documents/Bookmarked%20Practice%20Guidelines/ HCCUpdate2010.pdf. Here, we briefly describe only new or changed recommendations.

6,642 citations

Related Papers (5)
Frequently Asked Questions (1)
Q1. What are the contributions mentioned in the paper "Patients with advanced hepatocellular carcinoma need a personalized management: a lesson from clinical practice" ?

Giannini et al. this paper presented the Italian Liver Cancer ( ITA.LI.CA ) group for the first time.