1, How to adjuvant chemotherapy for colon cancer
There are two main principles in this process:
1. Find people who need adjuvant chemotherapy.
2. Look for patients who can really benefit from adjuvant chemotherapy, but obviously not everyone can finally benefit from chemotherapy. How to identify them? It depends on the predictors of curative effect.
Over the years, the exploration of adjuvant chemotherapy for stage ⅱ colon cancer has especially reflected this process.
"High Risk Factor" Oxaliplatin
"High-risk factors" aim to identify patients with high risk of recurrence and metastasis. At present, the "high-risk second stage" factors recognized by major global institutions and society include at least one of the following:
T4 tumor, tumor perforation, intestinal obstruction, poor histological differentiation (except MSI-H), vascular/nerve infiltration and lymph nodes smaller than 10.
Based on the current evidence, patients with these high risk factors can be used as predictors of the efficacy of oxaliplatin in adjuvant chemotherapy for stage II colon cancer because of their high risk of recurrence.
At present, there is no randomized controlled study based on clinical high-risk factors to predict the efficacy of fluorouracil adjuvant chemotherapy. MOSAIC study is the first RCT to prospectively include high-risk factors in the study. The results showed that compared with 5-FU/LV adjuvant chemotherapy, the 5-year DFS of FOLFOX4 was 83.7% and 79.9%, respectively, and the absolute benefit was 3.8%. The "high-risk stage II" group with high-risk factors was 82.3% and 74.6% respectively, and the absolute benefit was 7.7%.
The results show that the addition of oxaliplatin to adjuvant chemotherapy can not bring significant DFS benefits to the whole stage II patients, but it does bring DFS benefits similar to that of stage III to high-risk patients. Based on this study, the industry believes that high-risk phase II adjuvant chemotherapy can be used as phase III, and the regimen containing oxaliplatin is also regarded as an optional regimen for high-risk phase II colon cancer by NCCN and ESMO guidelines. However, for ordinary and low-risk patients without "high-risk factors",
MMR fluorouracil, oxaliplatin
This is the most concerned and frontier field at present, and it is also a breakthrough of individualized adjuvant chemotherapy for stage ⅱ colorectal cancer.
MMR status and MSIDNA mismatch repair (MMR) gene mutation or modification (such as methylation) will lead to MMR protein deletion and microsatellite instability (MSI).
MSI is the result of MMR deletion, which is caused by the insertion or deletion of DNA repeat units. Patients with MMR deletion (dMMR) belong to the same group as MSI-H (microsatellite high instability) in biology.
DMMR accounts for about 15% ~ 20% in stage ⅱ patients. A lot of evidence shows that the loss of MMR protein expression or MSI-H is a sign of good prognosis for patients with stage ⅱ colon cancer. Therefore, the expression of MMR protein can be detected by immunohistochemistry (IHC) to determine the prognosis. DMMR is a "low risk factor" for metastasis and recurrence of stage II colon cancer.
1 MMR and 5-FU adjuvant chemotherapy: still controversial.
Some studies have pointed out that MSI may be a predictor of the efficacy of adjuvant chemotherapy, and MSI colon cancer can not benefit from 5-FU chemotherapy. Sargent et al. also found similar results in a retrospective meta-analysis integrating data from several clinical studies, that is, dMMR colon cancer can not benefit from FU monotherapy, especially in phase II, and may also bring survival damage; On the contrary, patients with pMMR can obviously benefit from the same treatment.
In view of the above research results, NCCN guideline 20 10 lists MMR as a predictor of the efficacy of adjuvant chemotherapy, and recommends that all patients with stage ⅱ colon cancer be tested for MMR, and points out that patients with d MMR cannot benefit from adjuvant chemotherapy with fluorouracil alone.
However, contrary to Sargent's research results, QUASAR research analyzed the data of 19 13 cases of stage II colon cancer (half of the patients received adjuvant chemotherapy), and finally concluded that dMMR could not predict the lack of adjuvant chemotherapy for 5-FU. The results of PETACC-3(Tejparetal, 2009) also show that dMMR is only a prognostic indicator, not a prognostic indicator, and both MSI and MSS patients benefit from adjuvant chemotherapy.
In view of these inconsistent data, ESMO guidelines do not use MMR as a predictor of adjuvant chemotherapy for colon cancer.
Some people think that the predictive value of MMR in 5-FU adjuvant chemotherapy may be related to the molecular mechanism leading to MMR dysfunction. The dMMR of sporadic colorectal cancer is mainly caused by methylation of MLH 1 promoter, while the dMMR of Lynch syndrome is mainly caused by germline mutation. These differences may lead to different drug sensitivities.
It can be seen that whether dMMR can predict the insufficient efficacy of 5-FU adjuvant chemotherapy is still controversial in the industry. Whether it is necessary to treat sporadic and hereditary patients differently when facing the treatment choice of patients with dMMR phenotype in clinic is still inconclusive, which deserves further study.
The efficacy of 2.2. Preliminary advantages of MMR and oxaliplatin as adjuvant chemotherapy
There is no randomized controlled study on the relationship between MMR and FOLFOX (oxaliplatin /5-FU/LV) adjuvant chemotherapy.
A retrospective study (Zaananetal, 2009) found that MSI-H patients with stage III colon cancer benefited significantly from FOLFOX chemotherapy compared with 5-FU/LV chemotherapy. Several other retrospective studies have reached similar results. The data observed at present show that the benefit of adjuvant chemotherapy containing oxaliplatin has nothing to do with MSI status, and it can bring benefits compared with 5-FU/LV alone.
To sum up, although the predictive value of MMR is still controversial, it is currently considered to be mainly limited to fluorouracil monotherapy, especially for phase II patients. The existing evidence shows that dMMR/MSH-H can not benefit, and may even be harmful. For oxaliplatin, MSI status has nothing to do with the efficacy of adjuvant chemotherapy, and can all benefit.
Multi-gene detection: no advantages have been seen yet
Genetic testing has shown encouraging results in evaluating prognosis. With the opening of the era of precision medicine, I believe there will be progress in this area. At present, there are two most mature systems: OncotypeDX(GenomicHealth, Inc) gene detection technology for colon cancer and ColoPrint(Agendia) gene detection technology.
OncotypeDX quantitatively expressed 7 recurrence risk genes and 5 reference genes, and divided the recurrence risk into low, medium and high. After retrospective verification in QUASAR and NSABPC-07 studies, it was found that the 3-year recurrence rates of the three groups were 65,438+02%, 65,438+08% and 22% respectively.
Taking NSABPC-07 (injection of 5-Fu/LV oxaliplatin for adjuvant chemotherapy of stage II/III colon cancer) as an example, the value of this system in predicting the efficacy of adjuvant chemotherapy was analyzed retrospectively (YothersGetal, 20 13), and the conclusion was that it could not be used as a predictor of the efficacy of oxaliplatin adjuvant chemotherapy.
ColoPrint gene detection technology can quantitatively express 18 prognostic related genes and divide them into low-risk recurrence group and high-risk recurrence group. In the verification test, it is also found that different recurrence risks can be well identified. For stage II patients, the HR of recurrence rate in high-risk group and low-risk group was 3.34. ColoPrint has not been verified in RCT system to predict the efficacy of adjuvant chemotherapy.
What is the clinical decision of adjuvant chemotherapy for stage ⅱ colon cancer?
Staging, clinicopathological risk factors and MMR are the most important factors to be considered in decision-making. Of course, other factors such as the patient's physical function and accompanying diseases. It should be combined to fully communicate the advantages and disadvantages of adjuvant chemotherapy with patients.
For stage ⅱ colon cancer, there are two factors from the perspective of prognosis, namely MMR and clinical high-risk factors, and from the perspective of curative effect prediction, only MMR can provide reference. If MMR is normal, clinical decision-making at this time is not affected by MMR and can be carried out according to clinical routine.
1.dMMR
First, the prognosis is good, and second, dMMR shows that fluorouracil monotherapy is ineffective, which is the standard adjuvant chemotherapy scheme for most stage II colon cancer. In view of this, for patients with dMMR, adjuvant chemotherapy is generally not advocated, and simple observation is enough.
2. dMMR with clinical high risk factors.
At present, there is still controversy, because there are few such groups (the ratio of T4 to dMMR is about 1%), and there is still a lack of special research data, which needs to be considered in combination with other factors. According to the international knowledge in Europe and America, T4b is the most important clinical high-risk factor, and the weight of this factor will be greater than MMR (Figure 1).
That is to say, taking T4b as the main reference at this time, chemotherapy will be recommended, and other clinical high-risk factors give way to dMMR in treatment decision-making, and they also tend not to receive chemotherapy. However, due to the lack of RCT data support, these views have not yet reached a complete understanding, and there is no writing guide. Personally, I totally agree with this view, and clinical decision-making is also handled according to this idea.
In a word, the decision of adjuvant chemotherapy for dMMR with clinical high-risk factors is still controversial, but if chemotherapy is decided, the author advocates adopting a combination regimen containing oxaliplatin to avoid the possible resistance of dMMR to 5-FU.
2. How to prevent colon cancer
1. Not enough for dinner.
If you overeat for a long time and repeatedly stimulate the secretion of insulin, it will often aggravate the burden of insulin β cells, lead to failure and induce diabetes. At the same time, if you eat too much dinner, some protein can't digest and absorb it. Under the action of intestinal bacteria, toxic substances will be produced, and intestinal peristalsis will slow down during sleep, which may promote the occurrence of colorectal cancer by relatively prolonging the residence time of these substances in the intestine.
2. Dinner is not very sweet
Sugar is digested and decomposed into sugar and glucose, which are absorbed by the human body and converted into energy and fat respectively. Because exercise can inhibit insulin secretion, it can also inhibit the conversion of sugar into fat. Therefore, exercise immediately after taking white sugar can inhibit the increase of neutral fat concentration in blood. And rest immediately after eating sugar, the result is the opposite, and it will make people fat over time.
3. Dinner is not meat.
Medical research has found that people who often eat meat for dinner have three or four times higher blood lipids than those who often eat vegetarian food. People with hyperlipidemia and high blood pressure will add fuel to the fire if they often eat meat for dinner. Eating too many calories at dinner often leads to an increase in cholesterol, and too much cholesterol accumulates on the blood vessel wall, which will induce arteriosclerosis and coronary heart disease in the long run.