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NEJM Medical Frontiers invited Professor Mao Yilei, Department of Liver Surgery, Peking Union Medical College Hospital, to review ten influential studies in the field of liver cancer, biliary malignancy and pancreatic cancer in 2022 and clinical research questions
to be further explored.
NEJM Medical Frontiers is a collaboration between Jiahui Medical Research and Education Group (J-Med) and the New England Journal of Medicine (NEJM
).
For the fifth consecutive year, we have launched a clinical research inventory of all important disease areas, so stay tuned
.
is still a year of the new crown virus, and countless medical workers are busy and dedicated to the fight against Covid-19, and have made unremitting efforts
to understand and treat the new crown virus infection more clearly 。 However, the global medical community has also made excellent research results in clinical research on liver cancer, pancreatic cancer, and biliary system malignancies, and we have summarized the main developments in this extraordinary year as follows
.
The first-line treatment potential of pembrolizumab for liver cancer in advanced hepatocellular carcinoma is one of the most common malignant tumors worldwide and the leading cause of cancer-related
death [1
。 Among them, hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers[2].
At present, early diagnosis and screening are mainly carried out by laboratory detection of alpha-fetoprotein and medical imaging examination, but due to the difficulty of distinguishing from other diseases, the missed diagnosis rate is high [3-4].
Therefore, most Chinese HCC patients are advanced at the time of initial diagnosis and are not suitable for radical treatment
.
The prognosis of these patients is poor, so the search for effective treatments for advanced HCC has long been a hot spot [5].
In recent years, many treatments for advanced HCC have been used clinically, and oral tyrosine kinase inhibitors sorafenib [6,7] and lenvatinib [8] monotherapy have become first-line treatments
for advanced HCC.
Atezolizumab plus bevacizumab has also shown significant survival benefit and is the first-line treatment for many patients with unresectable HCC [9].
The KEYNOTE-224 trial is a phase 2 single-arm, open-label, multicenter clinical trial investigating the efficacy of pembrolizumab monotherapy in patients with advanced HCC who have not previously received systemic therapy [10].
The results showed that pembrolizumab monotherapy had a good objective response rate (ORR) and durable antitumor activity (ORR, 16%; Median duration of response [DOR], 16 months).
These findings support further evaluation of the efficacy
of pembrolizumab alone or in combination with other drugs for the treatment of advanced HCC.
However, due to the small number of patients included in this study (51), the study design being single-armed, and the subgroup analysis was conducted in only a smaller number of patients, the conclusions of this study cannot be directly interpreted as the real-world effect
of pembrolizumab monotherapy in patients with advanced HCC.
However, the KEYNOTE-224 study still proposes a new therapeutic idea
for the treatment of patients with advanced HCC.
Recent data suggest that HCC due to nonalcoholic steatohepatitis is becoming more common [11,12], and patients with this etiology may be considered for future inclusion in the participant population
.
Monotherapy with lenvatinib combined with arterial chemoembolization or as a first-line treatment for advanced hepatocellular carcinoma has become first-line treatment for advanced HCC [8], but in fact its efficacy alone is not very satisfactory, with a median overall survival (OS) of only 13.
6 months, so survival in these patients remains low [13].
Transarterial chemoembolization (TACE) has been shown to improve outcomes in patients with advanced HCC [14].
So, can lenvatinib plus TAGE (len-tace) bring more benefit to patients with advanced HCC than lenvatinib monotherapy?
In a multicenter, randomized, open-label, parallel-group, phase III trial published in 2022, a total of 338 patients were randomized to 12 centers in China, of whom 170 received lenvatinib-TACE and 168 received lenvatinib [15].
Results showed that median OS was significantly longer in the lenvatinib-TACE group (17.
8 vs.
11.
5 months; Risk ratio, 0.
45; P <0.
001).
<b24> The median progression-free survival (PFS) was 10.
6 months in the lenvatinib-TACE group and 6.
4 months in the lenvatinib group (hazard ratio, 0.
43; P< 0.
001).
<b26>
In addition, patients in the lenvatinib-TACE group had a higher ORR according to the revised Efficacy Evaluation Criteria for Solid Tumors (RECIST) (54.
1% vs.
25.
0%; P＜0.
001）
。 Therefore, we can be pleased to see from the results of this phase 3 trial that lenvatinib-TACE is a safe and effective treatment for patients with advanced HCC, with significant improvements
in OS, PFS, and ORR compared to lenvatinib monotherapy.
In addition, the median duration of treatment (8.
2 months) in the lenvatinib-TACE group was longer than in the lenvatinib group (5.
1 months), i.
e.
, lenvatinib-TACE combination therapy prolongs the treatment time and improves the treatment benefit
of patients with advanced HCC.
Moreover, in this study, 26 patients (15.
3%) in the lenvatinib-TACE group achieved curative surgical resection due to stage reduction, and 2 patients (1.
2%) achieved complete pathological remission
.
Therefore, lenvatinib-TACE combination therapy may be used as an effective downstage/outcome therapy in routine clinical practice, increasing the likelihood of subsequent radical therapy in patients with advanced HCC and improving survival outcomes
.
There were also some limitations in this study, such as the use of an open-label design; Secondly, all patients in this study are from China, and the efficacy for patients in other regions needs to be further verified
.
Nivolumab has a better safety profile for advanced hepatocellular carcinoma, and monotherapy with sorafenib and lenvatinib, as first-line treatment for advanced HCC, in addition to being unsurprisingly effective (median OS of sorafenib is 12.
3 months, and median OS of lenvatinib is 13.
6 months), its therapeutic safety also needs to be improved (49% of patients treated with sorafenib and 57% Patients treated with lenvatinib experienced grade 3 or more serious treatment-related adverse events) [16].
Therefore, people are constantly looking for drugs
that are more effective and have fewer adverse effects.
CheckMate 459 is a randomized, open-label, phase 3 clinical trial conducted in 22 countries and regions in Asia, Oceania, Europe, and North America that compares the efficacy and adverse effects of nivolumab monotherapy with sorafenib monotherapy in advanced HCC [17].
。 The results showed that the median OS was 16.
4 months (95% CI, 13.
9~18.
4) in the nivolumab group and 14.
7 months (95% CI, 11.
9~17.
2) in the sorafenib group (risk ratio, 0.
85; 95% CI, 0.
72~1.
02; P=0.
075).
The most common grade 3 or more serious treatment-related adverse events included sensory disturbance of palmoplantar redness and swelling (1 [<1%] vs.
52 [14%]) in the nivolumab group), elevated aspartate aminotransferases (22 [6%] vs.
13 [4%]), and hypertension (0 vs.
26 [7%]).
This study sheds some light on
us.
Although first-line nivolumab did not significantly prolong OS compared with sorafenib, the proportion of patients with grade 3 or 4 treatment-related adverse events was lower, suggesting that nivolumab is better tolerated and safe
in treating patients with advanced HCC.
Therefore, nivolumab may be an appropriate treatment option
for patients in whom tyrosine kinase inhibitors and antiangiogenic agents are strictly contraindicated or at significant risk.
But the studyLimited by its open-label approach, there may be bias in some data interpretation
.
Moreover, the proportion of patients in the sorafenib group receiving subsequent immunotherapy was higher than in the nivolumab group, which had an impact
on overall survival.
Based on the available evidence, the National Comprehensive Cancer Network (NCCN) clinical practice guidelines have listed nivolumab monotherapy as a first-line systemic regimen (for those who are not candidates for tyrosine kinase inhibitors or other antiangiogenic drugs).
Child-Pugh A or B advanced HCC patients), and as a follow-up treatment option (useful in some cases) after disease progression in patients with Child-Pugh B advanced HCC who have not previously received immune checkpoint inhibitor therapy [18].
However, nivolumab monotherapy for advanced HCC is not currently recommended by major guidelines in Europe or Asia [19-24].
Although the study has some flaws, it is a landmark study
in the field of advanced HCC treatment.
The efficacy of nivolumab monotherapy in the treatment of advanced HCC needs to be further studied, and we expect that its results will bring more opportunities and options
to cure patients with advanced HCC.
Hepatic artery infusion of oxaliplatin, fluorouracil and folinic acid has seen the greatest change in HCC treatment strategies in recent years as medium-term HCC
.
According to the American Association for the Study of Liver Diseases (AASLD) and the European Society for the Study of the Liver (EASL) guidelines, medium-term HCC is defined as multiple HCC, and the only recommended treatment is TACE
.
As the current standard of care for the treatment of medium-term HCC, TACE prolongs median OS by approximately 16 to 26 months
compared with untreated patients.
However, the efficacy of TACE is largely dependent on tumor size, with complete response rates significantly lower for large tumors than for small tumors (5 cm HCC vs.
small HCC, 25 versus 64 percent) [25].
Since the definition of medium-term HCC includes different patient populations and a wide range of tumor burdens, finding more effective treatments for such patients is an urgent challenge
.
A randomized, open-label, parallel-group phase 3 trial published by Professor Shi Ming's team of Sun Yat-sen University Cancer Center in 2022 compared the therapeutic effect of hepatic arterial infusion of oxaliplatin, fluorouracil and folinic acid (FOLFOX-HAIC) with TACE on medium-term HCC, and the results showed that the median OS of the FOLFOX-HAIC group was 23.
1 months (95% CI, 18.
5~27.
7).
The median OS of the TACE group was 16.
1 months (95% CI, 14.
3~17.
9) (hazard ratio, 0.
58; 95% CI, 0.
45~0.
75; P<0.
001<b20>).
EFFECTIVE RATES WERE HIGHER IN THE FOLFOX-HAIC GROUP THAN IN THE TACE GROUP (46% vs.
18%; P＜0 .
001）[26]
。 The incidence of serious adverse events was higher in the TACE group than in the FOLFOX-HAIC group (30% vs.
19%, P = 0.
03).
The results of this study first show that FOLFOX-HAIC as a first-line treatment has significant improvements
in OS, response rate, PFS and other aspects compared with TACE.
Second, FOLFOX-HAIC had fewer
serious adverse events than TACE.
Third, the potential curative surgical resection rate was significantly higher in the FOLFOX-HAIC group compared with the TACE group (24% vs.
12%), which significantly improved the survival benefit
of patients.
For patients with unresectable large-volume HCC without vascular invasion or extrahepatic metastases, FOLFOX-HAIC has shown superior efficacy and safety
compared with TACE.
For some patients with unresectable large-volume HCC, FOLFOX-HAIC may be an appropriate first-line locoregional intervention
.
However, this approach requires further prospective evaluation to understand how and whether it should be used instead of or in combination with a growing number of systemic therapies
targeting the same clinical indications.
Neoadjuvant chemotherapy for biliary malignant tumors
GEM/S-1 may improve the efficacy of marginal resectable hilar cholangiocarcinoma Hepatic hilar cholangiocarcinoma (PHC) is a common biliary malignant tumor, accounting for about 40%~60% of cholangiocarcinoma, and the incidence is increasing year by year, bringing heavy economic burden
to society and family.
Surgical resection is still the only treatment strategy for this complex condition [27,28], but due to the special anatomical location and complex biological characteristics of the tumor, even after the resection claimed to be "cured", the recurrence rate is high, about 55%~69% [29,30].
Therefore, the treatment of hilar cholangiocarcinoma cannot rely solely on surgery, but also requires multidisciplinary combined treatment
.
The use of chemotherapy or adjuvant surgery for unresectable hilar cholangiocarcinoma has been reported, but neoadjuvant chemotherapy (NAC) for resectable hilar cholangiocarcinoma has been rarely reported [31-33].
Matsuyama's team used GEM/S-1 as NAC to control local lesions and micrometastases of hilar cholangiocarcinoma, and conducted a prospective phase 2 trial to explore the effect of NAC on marginal hilar cholangiocarcinoma [34].
。 The results of the study showed that after NAC in 60 patients, 43 (71.
6%) could undergo surgery, and 10 of 17 palliative care patients found small distant metastases
.
Patients who completed all scheduled treatments had a 5-year survival rate of 36.
4%, median survival of 50.
1 months, and a margin-negative (R0) resection rate of 81.
3%, which was a significant improvement
over 5-year survival without NAC (67%).
The prognosis is relatively good
in cases where margins are resectable.
Therefore, GEM/S-1 as a preoperative NAC is well tolerated and safe in patients with hilar cholangiocarcinoma, and can improve the treatment effect
to a certain extent.
However, there are still some problems with preoperative chemotherapy for hilar cholangiocarcinoma, for example, NAC may lead to liver dysfunction that prevents the originally planned hepatectomy, and recurrent cholangitis during chemotherapy may prevent the completion of the established treatment
.
Therefore, biliary stenting is also required during NAC
.
In conclusion, although this study suggests the therapeutic significance of GEM/S-1 NAC for marginal resectable hilar cholangiocarcinoma and the improvement of patient outcomes, there are still many problems that need to be solved
.
Future prospective, randomized, multicenter trials are needed to ensure the effectiveness
of NAC for resectable hilar cholangiocarcinoma.
Duvalumab combined with gemcitabine and cisplatin may become the first-line treatment for advanced biliary cancer In recent years, the incidence of cholangiocarcinoma worldwide is increasing year by year, radical surgical resection is the only chance for long-term survival of cholangiocarcinoma patients, but 80%~90% of cholangiocarcinoma patients are unresectable advanced stage when they are first diagnosed [35].
。 The prognosis for advanced cholangiocarcinoma is poor, with a five-year survival rate of only about 5 percent, and its sole first-line standard of treatment (gemcitabine + cisplatin) has remained unchanged for many years [36].
Finding other scientifically effective treatments for advanced cholangiocarcinoma has always been a difficult
problem for medical practitioners.
With the continuous development of tumor immunology, cell biology, and molecular biology, immunotherapy has ushered in a new era
of treatment for various cancers, including advanced cholangiocarcinoma.
At present, many researchers have made breakthroughs
in this field.
As an example, in a phase 1 trial conducted in Japan in 2019, nivolumab in combination with gemcitabine and cisplatin showed good results with an ORR of 36.
7 percent and a median OS of 15.
4 months [37].
In 2022, Do-Youn Oh's team published a randomized, double-blind, Phase 3 clinical trial evaluating durvalumab in combination with gemcitabine and cisplatin versus placebo plus gemcitabine and cisplatin as late stageEfficacy and safety of first-line treatment in patients with biliary tract cancer [38].
The results showed that OS was significantly prolonged in the durvalumab group compared with placebo (hazard ratio, 0.
80; 95% CI, 0.
66~0.
97; P=0.
021).
The median OS was 12.
8 months (95% CI, 11.
1~14.
0) in the durvalumab group and 11.
5 months (95% CI, 10.
1~12.
5)
in the placebo group.
Grade 3 or 4 adverse events
occurred in 75.
7% of patients in the durvalumab group and 77.
8% in the placebo group.
The results of this study provide good evidence
for the use of durvalumab in combination with gemcitabine and cisplatin as first-line therapy for advanced biliary cancer.
The downside is that although the baseline characteristics of patients are generally balanced between treatment groups, the study tissue has a small sample size and MSI status test results are unknown in about 50% of patients in each treatment group, so the statistically significant improvement in OS observed in this study may not be attributable to the efficacy
of durvalumab alone 。 However, the study generally met the main goal of statistically significant improvement in OS in patients with advanced biliary tract cancer, and the incidence of grade 3 and 4 adverse events was similar in both groups, suggesting that durvalumab in combination with gemcitabine and cisplatin may be beneficial in patients with advanced biliary cancer and better improve patient outcomes
.
Impaired chromatin remodeling predicts the therapeutic efficacy of nivolumab in combination with modified gemcitabine and S-1 in advanced biliary cancer2022 Ming-Huang Chen's team announced a phase 2 trial called T1219, reporting the therapeutic efficacy of nivolumab in combination with modified gemcitabine and S-1 as a first-line treatment for advanced biliary cancer
。 The results of the study showed that this regimen had a good efficacy, with an ORR of 45.
9 percent, a median PFS of 9.
1 months, and a median OS of 19.
2 months [39].
It is worth mentioning that the incidence of hematological toxicity of grade 3 or higher in this regimen is less than 10%, which is much lower than current therapeutic data for gemcitabine and cisplatin [40-42].
In addition, the study also found a high frequency mutation of chromatin remodeling gene in advanced biliary tract cancer, up to 28.
9% (11/38) of patients with advanced biliary tract cancer had at least one cancer-causing chromatin remodeling gene truncation mutation, and PFS and OS were significantly better than those without
mutation.
This suggests that impaired chromatin remodeling may be a reliable and accurate genomic biomarker that is a good predictor of survival outcomes
.
Although the study was limited by its small sample size and the single-arm study could never confirm the superiority of this regimen over other regimens or evaluate the prognostic and predictive power of biomarkers, it did demonstrate to some extent that nivolumab in combination with modified gemcitabine and S-1 was a well-tolerated regimen with a good prognosis
.
Impaired chromatin remodeling has potential value in predicting the prognosis of chemotherapy and immunotherapy for advanced biliary cancer, but needs to be validated and explored
in larger cohorts.
Modified adjuvant therapy for pancreatic cancer
with folfirinox prolongs survival after surgery for pancreatic ductal carcinoma Pancreatic ductal carcinoma (PDAC) is a malignant solid tumor with a very poor prognosis, accounting for about 85% of pancreatic cancer [43], surgery is still an important means of treating early PDAC, but similar to cholangiocarcinoma, only 15%~20% of patients are in the early stage of diagnosis, and most patients are unresectable advanced stage at the time of initial diagnosis [44].
Although the level of diagnosis and treatment of pancreatic cancer has improved over the past 20 years, it is far from ideal, so there is an urgent need to find effective new treatments
.
Surgical resection alone has been shown to correlate with five-year overall survival (OS) by only 10 percent [45][46], and the addition of adjuvant chemotherapy after surgery significantly improves survival outcomes in patients undergoing PDAC resection [47-49].
。 In the CONKO-001 randomized trial, adjuvant gemcitabine for six months after PDAC resection significantly improved disease-free survival compared with observation alone (13.
4 versus 6.
9 months; P<0.
001) and OS (22.
8 vs.
20.
2 months; P=0.
01）[46]
。 In the past few years, gemcitabine has become the standard adjuvant treatment
after pancreatic cancer surgery.
A randomized, open-label Phase 3 clinical trial published in 2022 randomized 493 eligible patients (1:1) to receive adjuvant mFOLFIRINOX every 14 days for 24 weeks (12 cycles) or gemcitabine for 24 weeks [50].
。 The trial found that the median disease-free survival was 21.
4 months (95% CI, 17.
5-26.
7) vs.
12.
8 months (95% CI, 11.
6-15.
2) (hazard ratio, 0.
66; 95% CI, 0.
54~0.
82; P<0.
001) and 5-year disease-free survival of 26.
1% vs.
19.
0% in patients receiving modified folfirinox and gemcitabine chemotherapy.
The median OS was 53.
5 months (95% CI, 43.
5-58.
4) vs.
35.
5 months (95% CI, 30.
1-40.
3) (hazard ratio, 0.
68; 95% CI, 0.
54~0.
85; P=0.
001), and the 5-year OS rate was 43.
2% vs.
31.
4%.
Thus, modified FOLFIRINOX significantly prolonged OS (median survival, 53.
5 vs.
35.
5 months) compared with gemcitabine treatment, providing a better option
for postoperative adjuvant therapy with PDAC.
However, the study also has some limitations, such as the increasing number of elderly patients diagnosed with pancreatic cancer in routine practice, but only 20.
5% of the patients in the study are 70 years old or older, so it is not a good representation of the treatment effect
of this group of patients.
Efficacy of neoadjuvant therapy versus prior surgery for resectable and marginal resectable pancreatic cancer Approximately 15% of pancreatic cancer patients have resectable or marginally resectable pancreatic cancer, and although postoperative adjuvant chemotherapy has been shown to improve OS in patients after pancreatic cancer resection, approximately 50% of patients are unable to receive postoperative adjuvant chemotherapy due to early recurrence, surgical complications, or clinical deterioration
。 Therefore, neoadjuvant therapy may increase the proportion of patients actually receiving chemotherapy and improve microscopic R0 resection rates, thereby improving survival
.
However, whether neoadjuvant therapy is beneficial in resectable and marginal resectable pancreatic cancer remains controversial
.
A multicenter phase 3 PREOPAC trial in the Netherlands compared neoadjuvant therapy versus pre-operative surgery with better outcomes in patients with resectable and marginally resectable pancreatic cancer [51].
The results showed that the 5-year OS rate of neoadjuvant chemoradiotherapy + 4 cycles of adjuvant gemcitabine therapy after surgery was 20.
5% (95% CI, 14.
2~29.
8), and the 5-year OS rate of adjuvant gemcitabine 6 cycles after preoperative surgery + 6 cycles after surgery was 6.
5% (95% CI, 3.
1~13.
7).
Thus, neoadjuvant therapy had a long-term survival benefit compared with previous surgery (hazard ratio, 0.
73; P = 0.
025), with a 5-year OS rate showing a clinically relevant improvement
of 14%.
Moreover, some patients with early progression in the neoadjuvant group thus avoided ineffective surgical intervention
.
However, neoadjuvant therapy does not prevent early tumor progression, and further search for more effective treatment options
is needed.
Overall, the PREOPANC study confirmed that gemcitabine-based neoadjuvant chemoradiotherapy with surgery and adjuvant gemcitabine can improve long-term OS in patients with resectable and marginal resectable pancreatic cancer compared with previous surgery and adjuvant gemcitabine, and this study has some implications for the treatment regimen of patients with resectable and marginal resectable pancreatic cancer, which can be used as a clinical reference
.
However, the best new adjunct requires further study
.
Efficacy of stereotactic body radiation therapy + nivolumab + ipilimumab in patients with refractory metastatic pancreatic cancer because most patients with pancreatic cancer are advanced at the time of initial diagnosisMany patients have metastasized
.
There is currently no evidence that metastatic surgery improves OS rates in this patient population [52-56], but systemic therapy has been shown to improve OS and quality of life in patients with metastatic pancreatic cancer with 0~2 performance status in the Eastern United States Oncology Group (ECOG) [57-62].
A randomized Phase 2 clinical trial by Inna M.
Chen's team, published in 2022, compared stereotactic body radiation therapy (SBRT) + nivolumab and SBRT + nivolumab + ipilimumab in patients with
metastatic pancreatic cancer 。 The authors found that the clinical benefit rate (CBR) of patients receiving SBRT+ nivolumab was 17.
1% (8.
0%~30.
6%), and that of patients receiving SBRT+ nivolumab + ipilimumab was 37.
2% (24.
0%~52.
1%) [63].
Although the cohorts included in this study are two highly selected cohorts, which will limit the general applicability of the results to some extent, this still confirms to some extent that SBRT + nivolumab + ipilimumab shows better antitumor activity and safety in patients with refractory metastatic pancreatic cancer, and proposes new treatment ideas and treatment options
for the treatment of such patients 。 However, since SBRT is included in both groups, the exact contribution of radiotherapy to the efficacy of metastatic pancreatic cancer is unknown, and further research may focus on determining whether and how nivolumab + ipilimumab in combination with SBRT enhances antitumor activity and promotes disease remission
.
As a common malignant tumor, hepatobiliary and pancreatic malignant tumors have been seriously threatening human life and health
for many years 。 With the continuous progress and development of medicine, people's basic and clinical research on hepatobiliary and pancreatic malignant tumors is also deepening, and many views and ideas on their diagnosis and treatment are constantly changing
.
Tumor drugs have also gradually transitioned from the era of cytotoxic drugs dominated by chemotherapy drugs to the era of targeted therapy and immunotherapy characterized by precision therapy, and the treatment methods have gradually changed from monotherapy to combination therapy
.
Looking back at the ten most influential studies published in 2022, many scholars in the field of hepatobiliary and pancreatic tumors around the world have made significant progress in NAC and multi-method combination therapy, making outstanding contributions
to improving the diagnosis, treatment and research level of hepatobiliary and pancreatic tumors, further improving the quality of life and prolonging survival of patients.
It is expected that new clinical studies will bring more benefits to patients with hepatobiliary and pancreatic tumors in the future, and hope that global hepatobiliary and pancreatic tumor researchers will work together to contribute to the treatment of hepatobiliary and pancreatic tumors
.
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About the author
of Peking Union Medical College Hospital.
He is currently the vice chairman of the Liver Surgeon Committee of the Chinese Medical Doctor Association, the president of the Surgical Technology Innovation and Promotion Branch, the vice president of the Hepatobiliary and Pancreatic Surgery Department of the Chinese Association for the Elderly, and the standing member
of the Liver Cancer Professional Committee of the Chinese Anti-Cancer Association.
He is a member of the American Society for Gastrointestinal Surgery and the
American Nutrition Association.
He has been rated as one of the top ten outstanding professors
by the Department of Surgery of Peking Union Medical College Hospital three times.
Founder and editor-in-chief of Hepatobiliary Surgery and Nutrition (HBSN), the journal
SCI.
Completed residency training at Modbury Hospital, Australia in 1990; In 1997, he received his doctorate
in surgery from Lund University, Sweden, the most famous Nordic country.
In 1999, he completed his postdoctoral training at Harvard University and completed clinical training
in the Department of Oncology at Massachusetts General Hospital.
Director of Beijing Harvard Alumni Association (2nd, 3rd and 4th terms
).
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