A review of the weight study of advanced | liver cancer in ASCO
Last Update: 2020-06-19
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< br / >China's primary liver cancer patients account for more than 50% of the world's primary liver cancer (HCC) patients< br / > < br / >< br / > < br / > < br / > < br / > < br / > < br / > early diagnosis of cancer is a magic weapon to improve the survival and prognosis of cancer patientsThe cure rate of early cancer patients is much higher than that of late cancer patientsAlthough it is recommended that patients at high risk of liver cancer should be examined with or without AFP every two years, the detection rate of early liver cancer is still unsatisfactoryChalasani et alOf Indiana University School of Medicine carried out an international multicenter case-control study to collect blood samples from patients with liver cancer and controls (all patients suffered from cirrhosis or chronic HBV infection), evaluate a group of biomarkers including methylated DNA markers (MDMS) and proteins to detect the sensitivity of liver cancerThe levels of five MDMS, AFP and AFP-L3 were evaluated according to age and gender< br / > < br / > < br / > < br / > 136 cases of liver cancer (81 early stage: O / a of BCLC stage) and 401 controls were recruited in this studyThe specificity was set at 89%The researchers used gender, age, AFP and three MDMS (Hoxa1, tspyl5 and b3galt6) with high sensitivity to early liver cancer (> 70%)AUC of the model was 0.91 (95% CI 0.89-0.94), while AUC of galad or AFP was only 0.88 (95% CI 0.85-0.91) and 0.84 (95% CI 0.81-0.87)Moreover, the results of the model were not affected by the presence or absence of HBV infectionThe algorithm based on blood markers developed by < br / > < br / > < br / > chalasani et alIs more sensitive to detect early liver cancer than other existing blood markers, or can significantly affect the clinical diagnosis, treatment and prognosis of liver cancer< br / > Researchers from the cancer center of the National Taiwan University evaluated the effect of ctDNA monitoring on the response of 47 patients with unresectable liver cancer who had not been treated systematically They found that ctDNA can be used to detect the response and progression of liver cancer In this study, the researchers collected blood samples from patients on the first day of the first course (c1d1) and the first day of the fourth course (c4d1), respectively At c1d1, the median amount of ctDNA extracted from 2ml plasma sample was 25.7ng CtDNA was positive in 45 patients The ctDNA level detected in c1d1 may be related to tumor load The dynamic changes of ctDNA after treatment were related to the remission of c4d1 At c4d1, 70% of the patients with complete remission had negative ctDNA, while only 27%, 9% and 0% of the patients with partial remission, stable condition and progression had negative ctDNA The survival time of patients with ctDNA negative after treatment was longer < br / > < br / > For patients who need hepatectomy, the residual volume after hepatectomy should be evaluated before operation When the residual liver tissue can not be compensated after operation, postoperative liver failure may occur < br / > In 1986, Kinoshita performed PVE before hepatectomy for the first time In 2012, schnitzbauer, Professor of Medical College of Regensburg University, Germany, and others invented a new surgical method: Hepatectomy (Alpps) with liver segmentation and portal vein ligation, which is used for super large liver tumors or scattered tumor nodules that are considered impossible to be resected From 2014 to 2016, the Oriental hepatobiliary surgery hospital recruited 76 patients who could not directly resect liver tumor due to the lack of remaining liver tissue They were randomly divided into Alpps group or PVE group (38 cases each) to study the effect of these two treatment methods on the long-term prognosis of patients Compared with PVE group, almost all the patients in Alpps group were successful in staged hepatectomy (97.4% vs 65.8%) The 3-year overall survival rate (OS) of Alpps group was significantly better than that of PVE group (65.8% vs 42.1%) Although the incidence of major postoperative complications in Alpps group was higher than that in PvE group (54.1% vs 20.0%) In general, compared with PVE, the long-term overall survival prognosis of patients with liver cancer treated with Alpps is better, although the incidence of postoperative complications is also higher < br / > < br / > < br / > < br / > Sorafenib is still the standard first-line therapy for advanced liver cancer Donafenib is a new type of multi kinase inhibitor, which shows anti hepatoma activity in IB phase test A randomized phase II / III clinical trial was conducted in the oncology department of West China Hospital Affiliated to Sichuan University to further evaluate the efficacy of donafenib in the treatment of advanced unresectable or metastatic liver cancer From March 2016 to April 2018, 668 patients were recruited and randomly divided into donafenib group (0.2g) or sorafenib group (0.4g) The primary end point was overall survival (OS) In 659 intention to treat patients (328 in donafenib group and 331 in sorafenib group), the OS of donafenib group was significantly longer than that of sorafenib group (12.1 vs 10.3 months, P = 0.036), but there was no significant difference in progression free survival, objective remission rate and course control rate between the two groups The incidence of grade 3 and above adverse reactions in donafenib group and sorafenib group were 57.4% and 67.5%, respectively The common adverse reactions in donafenib group were skin reaction (50.5%), aspartate transaminase (40.5%), bilirubin (39.0%), thrombocytopenia (37.8%) and diarrhea (36.6%) Compared with sorafenib, donafenib can significantly improve the OS of patients with advanced liver cancer, and has good safety and tolerance Donafenib may be the first line therapy for advanced liver cancer In addition, another randomized placebo-controlled, double-blind phase III clinical trial in West China Hospital evaluated the efficacy of apatinib as a second-line therapy for advanced liver cancer From April 2014 to March 2017, 393 patients were enrolled in the study and randomly assigned (2:1) to the apatinib group (261; 750mg Oral 1 / day) or placebo group (132) The primary end point was overall survival (OS) As expected, the median OS of apatinib group was significantly higher than that of placebo group (8.7 vs 6.8 months, P = 0.048) In addition, the median progression free survival (PFS) of apatinib group was longer than that of placebo group (4.5 vs 1.9 months, P < 0.0001), and the objective remission rate was higher than that of placebo group (10.7% vs 1.5%) The incidence of treatment-related adverse reactions was 97.3% in apatinib group and 70.8% in placebo group The most common grade 3 / 4 adverse reactions were hypertension (27.6%), hand foot syndrome (17.9%), thrombocytopenia (13.2%) and neutropenia (10.5%) < br / > < br / > < br / > < br / > in a word, apatinib, as a second-line therapy for patients with advanced liver cancer, significantly prolonged their OS and PFS, and was well tolerated < br / > < br / > < br / > Tumor immunotherapy ranked first among the top ten scientific breakthroughs in Science in 2013 The preliminary study of Kelley et al From the University of California San Francisco showed that the combination of double immunocheckpoint inhibitors (ICI) t (anti-CTLA-4) and D (anti-PD-L1) in the treatment of advanced liver cancer achieved a better objective response rate (ORR) and good tolerance Therefore, a randomized extended cohort (including 4 treatment groups) was further developed to evaluate the efficacy of T and D as single drug therapy and T + D combined therapy for advanced liver cancer As of February 9, 2019, 332 patients were recruited and randomly divided into T300 + D group (t 300mg + D 1500mg), T75 + D group (t 75mg + D 1500mg), D single drug group (1500mg) or T single drug group (750mg) The median follow-up time of T300 + D group, T75 + D group, D single drug group and T single drug group were 11.7 months, 14.6 months, 8.9 months and 15.8 months, respectively In T300 + D group, Orr was the highest and OS was the longest The phase III study of T300 + D compared with D single drug treatment is in progress < br / > < br / > < br / > < br / > < br / > < br / > < br / > unfortunately, not all immunostaining point inhibitors have antitumor effects on all kinds of tumors Two three-stage clinical trials of immunocheckpoint inhibitors (ICI) in the treatment of liver cancer failed to reach its main end point, which led to doubts about the clinical activity of ICI in patients with liver cancer < br / > < br / > < br / > < br / > Yonsei cancer center in Seoul, South Korea, conducted a comprehensive study on the clinicopathological factors of 261 patients with liver cancer who were treated with nawumab, and estimated its correlation with the prognosis of the patients The researchers reviewed and analyzed more than 80 clinicopathological factors and classified them into 6 categories: demographic characteristics (16 items), basic experimental tests (19 items), tumor load (12 items), previous studies (12 items), treatment response (5 items) and toxicity (18 items) < br / > < br / > < br / > Median follow-up was 4.5 months, median progression free survival (PFS) and overall survival (OS) were 2.3 and 6.3 months, respectively The objective remission rate was 15% Subgroup analysis showed that liver compensatory function, low tumor load, low inflammatory markers and low intrahepatic tumor load were significantly correlated with OS longer A total of 456 independent tumors (249 in liver, 124 in lung, 35 in lymph node and 48 in others) were detected The specific remission rates among organs were different (liver 9%, lung 25%, lymph node 37%, other metastasis 15%) It was obvious that the response of intrahepatic tumor to nafumab was the worst To sum up, liver function, tumor range and load, as well as the number of lymphocytes in plasma are the key factors that determine the response of tumor to ICI There are differences in organ specificity in the antitumor immune response of ICI Compared with extrahepatic metastases, the response of hepatoma to nawumab is worse DNA (ctDNA) for monitoring efficacy of atezolizumab plus bevacizumab in patients with unresectable hepatocellular carcinoma (HCC) First Author: Chih-Hung Hs
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