Multidisciplinary tumor board is associated with improved survival in patients with hepatocellular carcinoma after liver transplantation

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) ranks as the sixth most common cancer and the third- leading cause of cancer-related deaths worldwide. The multidisciplinary tumor board (MDTB) has been recognized for improving outcomes in cancer management, but its role in patients with HCC undergoing liver transplantation (LT) remains underexplored.

AIM

To evaluate the impact of an MDTB on survival outcomes in patients with HCC undergoing LT.

METHODS

We retrospectively analyzed 393 patients with HCC who underwent LT at our institution from October 2015 to October 2021. Patients were categorized into the MDTB and non-MDTB groups. We compared preoperative and postoperative characteristics, overall survival (OS), and disease-free survival (DFS) between the two groups.

RESULTS

Within the University of California, San Francisco (UCSF) criteria, no significant differences in OS and DFS were noted between the MDTB and non-MDTB groups. However, for patients who exceeded the UCSF criteria, the MDTB group exhibited a substantial improvement in both OS and DFS. The 1-year, 3-year, and 5-year OS rates for the MDTB group in this subgroup were 88.68%, 75.29%, and 61.78%, respectively, compared to 83.02%, 64.07%, and 38.25%, respectively in the non-MDTB group. Similarly, DFS rates were 89.47%, 71.35%, and 63.52%, respectively, vs 82.18%, 53.78%, and 34.04%, respectively.

CONCLUSION

The MDTB approach was particularly beneficial for patients with HCC exceeding the UCSF criteria, significantly improving OS and DFS. These findings advocate for integrating MDTB into clinical practice for optimizing the management of high-risk patients with HCC undergoing LT.

Key Words: Multidisciplinary tumor board; Hepatocellular carcinoma; Liver transplantation; Survival outcomes; Retrospective study

Core Tip: This study evaluated the impact of a multidisciplinary tumor board (MDTB) on the survival outcomes of patients with hepatocellular carcinoma undergoing liver transplantation. While MDTB and non-MDTB groups showed similar outcomes within the University of California, San Francisco criteria, MDTB involvement significantly improved overall survival and disease-free survival in patients exceeding University of California, San Francisco criteria. By integrating expertise from various specialties, MDTB enhanced bridging therapies, perioperative management, and individualized treatment strategies, advocating for its adoption to optimize outcomes for high-risk patients with hepatocellular carcinoma undergoing liver transplantation.

INTRODUCTION

Hepatocellular carcinoma (HCC) ranks as the sixth most common cancer and the third-leading cause of cancer-related deaths worldwide, with mortality rates rising in many regions[1]. The majority of patients with HCC present with severe cirrhosis or liver dysfunction, complicating their management[2]. Liver transplantation (LT) is widely regarded as the optimal treatment for patients with cirrhosis and small HCC or for those with unresectable HCC and partial liver dysfunction[3]. However, LT for HCC faces challenges such as organ shortages, leading to prolonged waiting times, tumor progression, and missed transplant opportunities[4]. HCC presents a unique clinical challenge due to its complex nature characterized by diverse etiologies, atypical clinical presentations, aggressive malignancy, and chronic liver damage. These factors frequently render traditional, single-specialty therapeutic approaches inadequate[5]. To address these challenges, the multidisciplinary tumor board (MDTB) approach has emerged as a critical strategy in managing patients with HCC undergoing LT[6].

MDTB involves a team of multidisciplinary experts, including hepatologists, transplant surgeons, radiologists, oncologists, and pathologists, who collaboratively develop individualized treatment plans[7]. This approach integrates expert opinions from various fields, ensuring comprehensive, patient-centered care. While MDTB has gained international recognition for improving cancer treatment outcomes[8], its application in patients with HCC undergoing LT is not yet standardized, and its impact, particularly in patients exceeding the University of California, San Francisco (UCSF) criteria, remains underexplored. Previous studies have shown that MDTB can improve the coordination of care, facilitate optimal treatment decisions, and contribute to improved outcomes in patients with HCC[9,10]. This study aimed to fill this gap by assessing whether the MDTB approach enhances overall survival (OS) and disease-free survival (DFS) in patients with HCC undergoing LT, especially those exceeding the UCSF criteria.

MATERIALS AND METHODS

Patient selection

We retrospectively analyzed 393 patients who underwent orthotopic LT for HCC at our institution between October 2015 and October 2021. The patients were categorized into two groups: 117 patients (29.8%) received LT with MDTB involvement (MDTB group), and 276 patients (70.2%) underwent LT without MDTB participation (non-MDTB group). Inclusion criteria for both groups included: (1) Indication for LT; (2) Age ≥ 18 years; (3) Primary diagnosis of HCC without extrahepatic or distant metastasis; (4) A Model for End-Stage Liver Disease score < 25 with a stable clinical condition; and (5) Diagnosis based on imaging criteria [dynamic CT/magnetic resonance imaging (MRI)] and/or histopathological confirmation. All grafts used for LT were obtained from deceased donors. No organs from executed prisoners were used. All deceased donations complied with the China Organ Donation Program. This study was approved by the ethics committee of Tianjin First Central Hospital.

Data collection

Preoperative and postoperative characteristics, including demographics, tumor characteristics, and donor information, were collected and compared between the MDTB and non-MDTB groups. Imaging data (CT and MRI) of the chest, abdomen, and pelvis were analyzed to assess the number, size, and metastatic potential of hepatic tumors. Preoperative assessments were validated against postoperative pathological findings. Follow-up continued until the last census date on July 31, 2023.

Diagnosis criteria

HCC was diagnosed based on dynamic imaging criteria and/or histopathological findings. Specifically, imaging modalities, such as dynamic contrast-enhanced CT or MRI, were used to identify arterial phase hyperenhancement and venous phase washout, characteristic features of HCC. Histopathological confirmation was obtained when imaging findings were inconclusive or required further validation.

Multidisciplinary team meeting

Initiated in March 2018, MDTB meetings were held weekly and comprised hepatologists, transplant surgeons, diagnostic radiologists, sonographers, interventional radiologists, medical oncologists, pathologists, and coordinators. Cases were presented by the treating physician, with imaging reviewed by radiologists, followed by open discussions. For patients exceeding the UCSF criteria, MDTB recommendations often included bridging treatments such as transhepatic arterial chemoembolization (TACE) or radiofrequency ablation based on tumor characteristics and expected wait times for transplantation. Controversial cases were revisited in subsequent MDTB meetings. The MDTB guidelines considered for the effective management of HCC included international recommendations such as the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases guidelines.

Statistical analysis

Preoperative and postoperative characteristics were compared between the MDTB and non-MDTB groups using χ² tests or Fisher’s exact tests for categorical variables and t tests for continuous variables. OS and DFS were analyzed using Kaplan-Meier curves, with comparisons made using the log-rank test. Subgroup analyses were conducted for patients within and exceeding the UCSF criteria. A P value < 0.05 was considered statistically significant.

RESULTS

Preoperative characteristics

Table 1 and Table 2 summarize the demographic and clinical characteristics of the study population. Most patients in both groups had hepatitis B cirrhosis as the underlying liver disease, with similar Model for End-Stage Liver Disease scores and waiting times for LT. The UCSF criteria were met by 58.1% of patients in the MDTB group and 61.9% in the non-MDTB group (P = 0.4989). A higher percentage of patients in the MDTB group received bridging therapy (74.4%) compared to the non-MDTB group (50.4%, P = 0.021), with a significant difference in the use of TACE (55.6% vs 31.5%, P < 0.001). Additionally, 12% of patients had multifocal disease, and 8% had extrahepatic disease. No significant differences were observed in the remaining preoperative characteristics between the MDTB and non-MDTB groups.

Table 1 Patient and tumor characteristics.

Characteristic	MDTB group (n = 117)	non-MDTB group (n = 276)	P value
Gender, male/female	73/44	189/87	0.651
Age, years	52.7 ± 17.1	49.2 ± 15.8	0.219
Indication for transplantation
Hepatitis B cirrhosis	84 (71.8)	208 (75.4)	0.662
Alcoholic cirrhosis	18 (15.4)	39 (14.1)	0.772
Other	15 (12.8)	29 (10.5)	> 0.990
MELD score at transplantation	17.1 ± 4.7	16.5 ± 4.9	0.215
PreOP biology
Total bilirubin, μmol/L	79.5 ± 76.9	74.7 ± 68.2	0.841
Serum creatinine, μmol/L	86.1 ± 72.6	82.6 ± 66.3	0.377
INR	1.4 ± 0.6	1.5 ± 0.6	0.447
Plasma ammonia, μmol/L	39.7 ± 21.5	42.6 ± 23.4	0.669
AFP, ng/mL1	23.4 (7-194)	30.1 (7-388)	0.165
PIVKA-II, mAU/mL1	39.5 (19-372)	47.3 (21-463)	0.312
Waiting time for LT
From HCC diagnosis, months	3.3 ± 2.6	2.9 ± 2.5	0.153
From listing, days	47.8 ± 51.4	44.7 ± 48.8	0.571
Radiological characteristics
Number of nodules	2.4 ± 1.3	2.3 ± 1.3	0.486
Size of the largest nodule, mm	47.9 ± 18.3	45.6 ± 17.9	0.248
Multifocal tumors	41 (35)	88 (31.9)	0.652
UCSF criteria			0.499
Within UCSF criteria	68 (58.1)	171 (61.9)
Exceeding UCSF criteria	49 (41.9)	105 (38.1)
Bridging therapy	87 (74.4)	139 (50.4)	0.021
TACE	65 (55.6)	86 (31.5)	< 0.001
RFA	11 (9.4)	28 (10.1)	> 0.990
SBRT	2 (1.7)	3 (1.1)	0.637
Resection	4 (3.4)	8 (2.9)	0.756
Other	5 (4.3)	14 (5.1)	> 0.990
Pathological characteristics
Poorly (Edmonson grade III/IV)	56 (47.8)	129 (46.7)	0.912
(Micro-) vascular invasion	37 (31.6)	82 (29.7)	0.719
Capsular invasion	33 (28.2)	77 (27.9)	> 0.990

Data are presented as n (%).

¹Data presented as median (quartile).

AFP: Alpha-fetoprotein; HCC: Hepatocellular carcinoma; INR: International normalization ratio; LT: Liver transplantation; MDTB: Multidisciplinary tumor board; MELD: Model for End-Stage Liver Disease; OP: Operative; PIVKA-II: Protein induced by vitamin K absence or antagonists-II; RFA: Radiofrequency ablation; SBRT: Stereotactic body radiation therapy; TACE: Transhepatic arterial chemoembolization; UCSF: University of California, San Francisco.

Table 2 Donor characteristics.

Characteristics	MDTB group (n = 117)	non-MDTB group (n = 276)	P value
Gender, male/female	84/33	179/97	> 0.990
Age, years	41.5 ± 16.9	43.3 ± 17.2	0.665
Cause of death
Cerebral trauma	65 (55.6)	148 (53.6)	> 0.990
Cerebrovascular accident	27 (23.1)	53 (19.2)	0.792
Brain tumor (glioma)	11 (9.4)	33 (11.9)	0.735
Hypoxic brain injury	5 (4.3)	20 (7.2)	0.672
Other	9 (7.7)	22 (7.9)	> 0.990
ICU stay, days	2.85 ± 2.05	2.93 ± 2.24	0.798

Data are presented as n (%). ICU: Intensive care unit; MDTB: Multidisciplinary tumor board.

Postoperative outcomes

Table 3 presents the postoperative outcomes. The incidence of grade III/IV complications did not differ significantly between the MDTB group (20.5%) and the non-MDTB group (25.7%, P = 0.304). Postoperative mortality rates were 7.7% in the MDTB group and 10.1% in the non-MDTB group (P = 0.572), with no significant difference in re-transplantation rates between the groups (10.3% vs 8.3%, P = 0.563).

Table 3 Patient outcomes.

Outcomes	MDTB group (n = 117)	non-MDTB group (n = 276)	P value
Complications grade III/IV	24 (20.5)	71 (25.7)	0.304
Post-operative deaths	9 (7.7)	28 (10.1)	0.572
Tumor progression/MOF	2 (1.7)	10 (3.6)
Sepsis	3 (2.6)	9 (3.2)
ARDS	2 (1.7)	4 (1.4)
Sudden cardiac arrest	1 (0.8)	3 (1.1)
GVHD	1 (0.8)	2 (0.7)
Re-transplantation	12 (10.3)	23 (8.3)	0.563
Hepatic graft dysfunction	6 (5.1)	10 (3.6)
Cholestatic graft dysfunction	4 (3.4)	9 (3.3)
Hepatic artery thrombosis	2 (1.7)	4 (1.4)
Tumor recurrence	24 (20.8)	87 (31.5)	0.104
Liver only	8 (6.8)	26 (9.4)
Liver and other	7 (5.9)	24 (8.7)
Other	14 (11.9)	37 (13.4)
Recurrence time, months	28.7 ± 14.9	21.5 ± 10.3	< 0.001

Data are presented as n (%). ARDS: Acute respiratory distress syndrome; GVHD: Graft versus host disease; MDTB: Multidisciplinary tumor board; MOF: Multiple organ failure.

Tumor recurrence and survival outcomes

Tumor recurrence occurred in 20.8% of patients in the MDTB group and 31.5% in the non-MDTB group (P = 0.104), with the MDTB group showing a significantly longer mean recurrence time (28.7 ± 14.9 months vs 21.5 ± 10.3 months, P < 0.001). No significant differences in OS and DFS were found between the MDTB and non-MDTB groups (Figure 1), and differences between the two groups were even smaller within the UCSF criteria (Figure 2). However, for patients exceeding the UCSF criteria, the MDTB group demonstrated significantly better survival outcomes. The 1-year, 3-year, and 5-year OS rates for this subgroup in the MDTB group were 88.68%, 75.29%, and 61.78%, respectively, compared to 83.02%, 64.07%, and 38.25%, respectively, in the non-MDTB group (P = 0.017). Similarly, the 1-year, 3-year, and 5-year DFS rates were significantly higher in the MDTB group, with rates of 89.47%, 71.35%, and 63.52%, respectively, compared to 82.18%, 53.78%, and 34.04%, respectively, in the non-MDTB group (P = 0.007) (Figure 3).

Figure 1 Multidisciplinary tumor board vs non-multidisciplinary tumor board. A: Overall survival; B: Disease-free survival. MDTB: Multidisciplinary tumor board.

Figure 2 Multidisciplinary tumor board vs non-multidisciplinary tumor board. These results indicate patients that were within the University of California, San Francisco (UCSF) criteria. A: Overall survival; B: Disease-free survival. MDTB: Multidisciplinary tumor board.

Figure 3  Multidisciplinary tumor board vs non-multidisciplinary tumor board. These results indicate patients that exceeded the University of California, San Francisco (UCSF) criteria. A: Overall survival; B: Disease-free survival. MDTB: Multidisciplinary tumor board.

DISCUSSION

This study highlighted that an MDTB approach significantly improved OS and DFS in patients with HCC undergoing LT, particularly in those exceeding the UCSF criteria. The holistic approach of the MDTB, integrating expertise from hepatologists, transplant surgeons, radiologists, oncologists, and pathologists, allows for comprehensive treatment planning, enhancing both preoperative and postoperative care. The MDTB approach proved to be especially effective for patients exceeding UCSF criteria, as demonstrated by the improved 1-year, 3-year, and 5-year OS rates in this subgroup compared to the non-MDTB group (Figure 2). Similarly, the 1-year, 3-year, and 5-year DFS rates were significantly higher in the MDTB group. This improvement is primarily attributed to the multidisciplinary evaluation of the MDTB, which facilitates individualized treatment plans, bridging therapies, and careful perioperative management. A significantly higher rate of bridging therapy was noted in the MDTB group (74.4%) compared to the non-MDTB group (50.4%) (Table 1). Bridging therapies such as TACE and radiofrequency ablation help control tumor progression during the waiting period for transplantation, reducing the risk of progression and enhancing post-transplant outcomes. This was particularly evident for patients with advanced-stage HCC or multifocal disease, who benefitted from the tailored interventions of the MDTB.

The role of the MDTB in individualized decision-making is crucial, especially for patients with more advanced disease or complex tumor characteristics. This indicates that comprehensive assessment and tailored treatment strategies of the MDTB play a significant role in improving outcomes for high-risk patients. Additionally, the mean recurrence time was significantly longer in the MDTB group (28.7 ± 14.9 months) compared to the non-MDTB group (21.5 ± 10.3 months, P < 0.001), emphasizing the effectiveness of the MDTB in managing recurrence risk through coordinated perioperative care. MDTB involvement also ensures optimal timing for transplantation and donor selection. The multidisciplinary nature of MDTB allows for thorough evaluation of each patient’s condition, enabling informed decisions that contribute to improved OS and DFS rates. The recurrence-free survival benefit observed in the MDTB group further supports the value of coordinated, multidisciplinary care in minimizing recurrence and improving long-term outcomes (Figure 3). This benefit is consistent with findings from other cancer types, such as colorectal cancer with liver metastases and lung cancer, where MDTB interventions have led to improved survival and reduced recurrence rates.

Finally, while MDTB implementation is resource-intensive, its long-term cost-effectiveness cannot be overlooked. Clinical pharmacists’ involvement in MDTB has been found to reduce medication-related issues, thereby optimizing treatment and improving cost-effectiveness. This study supports the integration of MDTB into clinical practice, particularly for high-risk patients with HCC who benefit significantly from comprehensive, multidisciplinary management that extends beyond conventional single-specialty care.

CONCLUSION

The integration of a MDTB into the treatment protocol for patients with HCC undergoing LT markedly improved OS and DFS, especially in patients who exceeded the UCSF criteria. This study strongly advocates for the broader adoption of MDTB in clinical practice, not only as a means to optimize the management of high-risk patients with HCC but also as a model for enhancing interdisciplinary collaboration in complex oncological care.

ACKNOWLEDGEMENTS

We thank the staff of the Department of Liver Transplantation, Tianjin First Center Hospital, for their invaluable contributions to this study.