The patient was a 62-year-old male with a history of hepatitis B and liver cirrhosis. Further CT examination revealed a 16 X 13.5 cm large mass in the right lobe of the liver (Figure 1), and he was admitted to the hospital for further diagnosis and treatment.
Figure 1: A large 16 X 13.5 cm mass in the right lobe of the liver
After admission, AFP: 12947.3 ug/l (normal value, <8.1); hepatitis B surface antigen (+); hepatitis C antibody (-); glutathione aminotransferase: 76 IU/l; glutamic oxalacetic aminotransferase: 56 IU/l; gamma-glutamyl transpeptidase: 52 IU/l; no abnormalities in routine blood, renal function, chest X-ray, etc.
Clinical diagnosis: hepatocellular carcinoma; hepatitis B; liver cirrhosis.
The treatment plan for this patient was combination therapy, including.
1, hepatic artery chemoembolization (TACE)
2.Oxaliplatin (L-OHP) systemic intravenous chemotherapy
3, recombinant human p53 adenovirus (p53) combined with 5-fluorouracil 5-Fu hepatic artery perfusion
Treatment course.
In order to facilitate the description, the day of treatment start was set as day 0, and the subsequent times of treatment process in this paper were taken as the base. The following table + pictures list the treatment process, AFP changes and tumor changes.
Time (days)
(counted from the start of treatment)
Treatment method
AFP (μg/L)
0
TACE+p53
12947.3
Figure 2: Hepatic arteriogram shows rich blood supply to the tumor in a reticular pattern
Time (days)
(from the start of treatment)
Treatment
AFP (μg/L)
0
TACE+p53
12947.3
2
L-OHP (IV)
6
13322.3
16
TACE+p53
6260.5
Figure 3: The mass was smaller than before, about 14 X 11.5 cm, and the blood supply was significantly reduced on the second pre-TAC imaging
After the second TAC, a hepatic artery cartridge was placed, and thereafter all drugs except L-OHP were given through the cartridge.
Time (days)
(counted from the start of treatment)
Treatment
AFP (μg/L)
0
TACE+p53
12947.3
2
L-OHP (IV)
6
13322.3
16
TACE+p53
6260.5
26
L-OHP(IV)
28
p53
34
5170.2
35
p53
118
236.9
A rapid decrease in AFP can be seen. The CT was repeated on day 119 as follows.
Figure 4: The tumor is significantly smaller than before, about 8 X 6 cm in size, with little blood supply.
Time (days)
(counted from the start of treatment)
Treatment
AFP (μg/L)
0
TACE+p53
12947.3
2
L-OHP (IV)
6
13322.3
16
TACE+p53
6260.5
26
L-OHP(IV)
28
p53
34
5170.2
35
p53
118
236.9
125
p53+5-Fu
131
p53+5-Fu
153
28.6
155
p53+5-Fu
A rapid decrease in AFP can be seen. The CT was repeated on day 161 as follows.
Figure 5: The tumor continues to shrink and is approximately 6 X 5 cm in size with little blood supply.
Time (days)
(counted from the start of treatment)
Treatment
AFP (μg/L)
0
TACE+p53
12947.3
2
L-OHP (IV)
6
13322.3
16
TACE+p53
6260.5
26
L-OHP(IV)
28
p53
34
5170.2
35
p53
118
236.9
125
p53+5-Fu
131
p53+5-Fu
153
28.6
155
p53+5-Fu
162
p53+5-Fu
205
19.8
208
p53+5-Fu
214
p53+5-Fu
279
4.8
The last treatment (p53+5-Fu by cartridge infusion) was performed on day 214, with regular follow-up thereafter. AFP can be seen to be decreasing rapidly and has dropped to normal. The CT was repeated on day 282 as follows.
Figure 6: The tumor continues to shrink and is approximately 5 X 3.5 cm in size with little blood supply.
Time (days)
(counted from the start of treatment)
Treatment
AFP (μg/L)
0
TACE+p53
12947.3
2
L-OHP (IV)
6
13322.3
16
TACE+p53
6260.5
26
L-OHP(IV)
28
p53
34
5170.2
35
p53
118
236.9
125
p53+5-Fu
131
p53+5-Fu
153
28.6
155
p53+5-Fu
162
p53+5-Fu
205
19.8
208
p53+5-Fu
214
p53+5-Fu
279
4.8
358
2.7
It can be seen that AFP is stable at normal level. The CT was repeated on day 363 as follows.
Figure 7: Although treatment has been discontinued, the tumor continues to shrink and is approximately 4.5 X 3.5 cm in size with little blood supply.
Time (days)
(counted from the start of treatment)
Treatment
AFP (μg/L)
0
TACE+p53
12947.3
2
L-OHP
6
13322.3
16
TACE+p53
6260.5
26
L-OHP
28
p53
34
5170.2
35
p53
118
236.9
125
p53+5-Fu
131
p53+5-Fu
153
28.6
155
p53+5-Fu
162
p53+5-Fu
205
19.8
208
p53+5-Fu
214
p53+5-Fu
279
4.8
358
2.7
455
3.3
It can be seen that AFP is stable at normal level. The CT was rechecked on day 456 as follows.
Figure 8: Although the treatment has been stopped, the tumor continues to shrink and is about 4 X 3.5 cm in size, and the blood supply is still low.
The repeat CT on day 553 is as follows.
Figure 9: The tumor continued to shrink, about 4 X 3 cm in size, and the blood supply was still low.
Time (days)
(counted from the start of treatment)
Treatment
AFP (μg/L)
0
TACE+p53
12947.3
2
L-OHP
6
13322.3
16
TACE+p53
6260.5
26
L-OHP
28
p53
34
5170.2
35
p53
118
236.9
125
p53+5-Fu
131
p53+5-Fu
153
28.6
155
p53+5-Fu
162
p53+5-Fu
205
19.8
208
p53+5-Fu
214
p53+5-Fu
279
4.8
358
2.7
455
3.3
638
1.3
828
4.2
It can be seen that AFP is stable at normal level. The CT was repeated on day 828 as follows.
Figure 10: The tumor continues to shrink, about 3 X 2 cm in size, and the blood supply is still low.
The last treatment was performed on day 214. The AFP has been stable in the normal range since it dropped to normal on day 279, and the mass is progressively shrinking, can we assume that the patient has no more live tumor cells in her body?
Putting the above pictures together to see the course of the mass.
Discussion.
1. TACE is still an important treatment for inoperable hepatocellular carcinoma.
2. systemic intravenous chemotherapy for hepatocellular carcinoma: I have to quote from a report that
At the 2010 ASCO Annual Meeting, Professor Qin Shukui, Director of the Collaborative Specialty Committee of Clinical Oncology (CSCO) of the Chinese Anti-Cancer Society and member of the PLA Nanjing Bayi Hospital, gave a congress report entitled “Phase III Clinical Study of Asian Patients with Advanced Liver Cancer Receiving FOLFOX Regimen Versus Doxorubicin Systemic Chemotherapy (EACH)”. A total of 371 patients with locally advanced or metastatic liver cancer were enrolled in the study and randomized to receive either the FOLFOX4 (oxaliplatin + 5-fluorouracil + calcium folinic acid) regimen or doxorubicin. The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), remission rate (RR), disease control rate (DCR), and safety.
Analysis of the data as of December 31, 2009, showed positive results for all primary and secondary endpoints. OS was 6.5 months and 4.9 months (P=0.04), PFS was 3.0 months and 1.8 months (P=0.0003), objective remission rates were 8.7% and 2.8% (P=0.01) in the FOLFOX and doxorubicin groups, respectively. DCR was 53.3% and 32.6% (P<0.0001). Encouragingly, the adverse effects in the FOLFOX group were not significantly different from those in the doxorubicin group, except for the occurrence of mild hand and foot numbness.
The significance of this study: First, this is a large clinical trial in the field of systemic chemotherapy, both for the oxaliplatin-containing regimen and for the doxorubicin regimen, which is currently the largest international multicenter randomized controlled study with the largest number of enrolled cases worldwide. Second, this study demonstrated for the first time the survival benefit of systemic chemotherapy for patients with advanced hepatocellular carcinoma. Third, doxorubicin was selected as a positive control rather than placebo in the control group. Fourth, half of the patients in the study were patients who failed local treatment such as surgery and intervention. The significance is that FOLFOX can be used as a first-line treatment option for patients who cannot receive local treatment, and as a second-line treatment option for those who failed local treatment. Fifth, this is a large international clinical study with positive results by the first principal investigator (PI), a mainland Chinese expert, over a period of 4 years. The study was also supported and guided by Professor Sun Yan, a member of the Chinese Academy of Engineering. (Wang Glistening from Chicago, USA)
3. About p53 gene therapy
In response to this question, there is a controversy.
”The p53 gene is the gene with the highest relevance to human tumors found so far. …. The wild-type p53 gene is an oncogene, and its inactivation plays an important role in tumor formation. …. The p53 gene is associated with 50% of all human tumors, including liver cancer, breast cancer, bladder cancer, stomach cancer, colon cancer, prostate cancer, soft tissue sarcoma, ovarian cancer, brain tumors, lymphocytic tumors, esophageal cancer, lung cancer, osteogenic sarcoma, etc.” (from Baidu.org: http://baike.baidu.com/view/ 1071670.html)
A large number of preclinical studies have confirmed the inhibitory effect of wild-type p53 gene on a variety of malignant tumors, and the indication on the instruction sheet of recombinant human p53 adenovirus injection (Imazan) is head and neck tumors.
I myself have also communicated with some domestic experts on the efficacy of this drug, the treatment of malignant tumors is a comprehensive treatment, p53 gene combined with radiotherapy, heat therapy and other treatments in some patients have achieved better results, Beijing Cancer Hospital Professor Zhang Shanwen and Fujian Cancer Hospital Professor Pan Jianji and other experts to complete the recombinant human p53 adenovirus injection (this year and raw) combined with radiotherapy for the treatment of advanced The results of the study on the combination of recombinant human p53 adenovirus injection (Imazan) with radiotherapy for advanced nasopharyngeal cancer were published in the Journal of Clinical Oncology. I have also seen in clinical application that some patients have better results with this drug, while others have poorer results, and there is no significant correlation between clinical observation and whether the p53 gene is mutated. The signaling of tumor cells is a three-dimensional network, and there are differences in signaling in different tumors and even different types of the same tumor. p53 is a point in this three-dimensional network system, and its role may be different in different tumors and different types of the same tumor. Personally, I think the research of sensitive markers should be carried out as soon as possible for this drug, that is, whether a marker (such as a certain molecule) can be found through research to determine whether the application of the drug is effective, so that this marker can be tested first, and if it is expected to be effective, the drug will be used; if it is expected to be ineffective, it will not be used. Just like the EGFR mutation test for lung cancer patients, after all, this drug is more expensive.