[Effect of chemotherapy in primary tumor of MSI-H colon cancer aged 50 years or younger].
Noriyasu ChikaKeiichiro IshibashiKensuke KumamotoNorimichi OkadaOkihide SuzukiSatoshi HatanoKunihiko AmanoTakeaki MatsuzawaKouki KuwabaraJun SobajimaYoichi KumagaiHiroyuki BabaNorihiro HagaTakeo Iwama∥Hideyuki IshidaShigehisa InokumaIkuya Takeuchi
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Microsatellite instability( MSI) in colorectal carcinoma is reportedly associated with resistance to 5-fluorouracil-based chemotherapy. Moreover, colorectal cancer patients aged ≤ 50 years could potentially have Lynch syndrome. In the present study, we examined 11 colorectal cancer patients with unresectable Stage IV disease who underwent resection of the primary tumor between January 2006 and December 2012. The relationship between the MSI status and the efficacy of first- line oxaliplatin-based chemotherapy was retrospectively examined. The MSI status included MSI-H in 1 patient, MSS-L in 2 patients, and MSS in 8 patients. The MSI-H in 1 patient was associated with familial adenomatous polyposis. Following chemotherapy, among 8 MSS patients, 3 showed stable disease (SD) and 1 showed partial response (PR). Moreover 2 MSH-L patients and 1 MSI-H patient showed progressive disease (PD) after chemotherapy. However, additional data collection is required to determine the effect of oxaliplatin-based chemotherapy for MSS-H or MSS-L colorectal patients aged ≤ 59 years.Keywords:
Microsatellite Instability
Primary tumor
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The present study investigated the expression of excision repair cross-complementing gene 1 (ERCC1) and thymidylate synthase (TYMS) in patients with colorectal cancer and the predictive value of chemotherapy. Eighty patients with colorectal cancer chemotherapy admitted to Binzhou Medical University Hospital from June 2013 to June 2015 were randomly selected, and 80 cancer tissues and 68 adjacent tissues were taken for analysis. RT-qPCR was used to detect ERCC1 as well as the expression level of TYMS. The relationship of the expression level with the chemotherapy efficacy, clinical pathology and survival time in colorectal cancer patients receiving standard chemotherapy, was compared. The expression of ERCC1 and TYMS mRNA in cancer tissues was significantly higher than that in the adjacent tissues (P<0.05). There was no correlation between ERCC1 mRNA expression, TYMS mRNA and clinicopathological features of colorectal cancer (P>0.05). The predictive effect of ERCC1 on colorectal cancer chemotherapy was 0.919 (95% CI, 0.862-0.976), P<0.001. The AUC of TYMS for predicting the efficacy of chemotherapy on colon cancer was 0.831 (95% CI, 0.735-0.926), and both had higher predictive values. The expression levels of ERCC1 and TYMS mRNA in 80 patients with colorectal cancer were divided into the low and high expression groups. The 3-year survival rate of patients in the low expression group was significantly higher than that in the high expression group, and the difference between the two groups was statistically significant (P<0.05). ERCC1 and TYMS had a high predictive value for the efficacy of chemotherapy in patients with colorectal cancer, and patients with lower expression of ERCC1 and TYMS had improved 3-year survival rates than patients with higher expression. Therefore, for patients with colorectal cancer, ERCC1 and TYMS can be used as predictors of the efficacy of chemotherapy.
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Microsatellite instability( MSI) in colorectal carcinoma is reportedly associated with resistance to 5-fluorouracil-based chemotherapy. Moreover, colorectal cancer patients aged ≤ 50 years could potentially have Lynch syndrome. In the present study, we examined 11 colorectal cancer patients with unresectable Stage IV disease who underwent resection of the primary tumor between January 2006 and December 2012. The relationship between the MSI status and the efficacy of first- line oxaliplatin-based chemotherapy was retrospectively examined. The MSI status included MSI-H in 1 patient, MSS-L in 2 patients, and MSS in 8 patients. The MSI-H in 1 patient was associated with familial adenomatous polyposis. Following chemotherapy, among 8 MSS patients, 3 showed stable disease (SD) and 1 showed partial response (PR). Moreover 2 MSH-L patients and 1 MSI-H patient showed progressive disease (PD) after chemotherapy. However, additional data collection is required to determine the effect of oxaliplatin-based chemotherapy for MSS-H or MSS-L colorectal patients aged ≤ 59 years.
Microsatellite Instability
Primary tumor
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Colorectal cancer is the third most commonly diagnosed cancer in males and the second in females, with over 1.2 million new cancer cases and 608,700 cancer related deaths in 2008 [1]. Despite the advances being made in early detection of colorectal cancer, approximately half of all patients develop metastatic disease [2]. The prognosis for these patients is poor, although palliative chemotherapy has been shown to be able to prolong survival and to improve the quality of life compared with the best supportive care [3]. Chemoresistance of cancer cells to chemotherapeutics is a main obstacle in chemotherapy to a successful outcome in first line therapy. It has been hypothesized that selection pressure resulting from tumor internal evolution can lead to subpopulations of cell clones, carrying certain cellular mechanism that can be summarized under the term “intrinsic chemoresistance.” Cellular mechanisms of intrinsic chemo resistance are mainly characterized by the fact that they lead to increased tolerance of cancer cells to chemotherapeutics. These cells are most likely to survive first line chemotherapy and arise as recurrence disease.
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Surgical oncology
Circulating tumor DNA
Adjuvant Chemotherapy
Primary tumor
Minimal Residual Disease
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The methylated septin 9 (mSEPT9) assay was the first blood-based test approved by the United States Food and Drug Administration as a colorectal screening test. However, the diagnostic and prognostic role of preoperative mSEPT9 for colorectal cancer (CRC) in Chinese patients is still unknown.To improve the understanding of diagnostic and prognostic factors, serum mSEPT9 was detected in Chinese CRC patients.A retrospective analysis of 354 cases, of which 300 had CRC and 54 were normal, was performed in China. Patients' characteristics, treatments, and laboratory data, including age, the date of surgery, Union for International Cancer Control (UICC) stages, distant metastasis (M), and so on, were collected. Methylation levels of SEPT9 were quantified by quantitative, methylation-specific polymerase chain reaction before surgery. In addition, the effects of mSEPT9 on the occurrence and prognosis of 330 CRC cases from The Cancer Genome Atlas (TCGA) database were evaluated using bioinformatics analyses. Potential prognostic factors for overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier univariate analysis.In Chinese CRC patients, positive mSEPT9 was strongly associated with advanced UICC stages, deeper invasion by the primary tumor, and more distant metastasis. Methylation levels of SEPT9 were stage-dependent and showed a stepwise increase in UICC stages (I-IV), primary tumor categories (T1-T4), regional node categories (N0-N2), and distant metastasis categories (M0-M1). The patients with positive mSEPT9 showed a tendency toward lower PFS. After analyzing TCGA clinical data, the high mSEPT9 group was found to be obviously correlated only with more distant metastasis. The patients with high mSEPT9 levels showed a tendency toward lower OS. Besides, nine meaningful mSEPT9 sites were found to provide guidance for the follow-up studies.MSEPT9 analysis may add valuable information to current tumor staging. Serum mSEPT9 in Chinese CRC patients appears to offer promising novel prognostic markers and might be considered for monitoring CRC recurrence.
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Microsatellite Instability
Distant metastasis
Primary tumor
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Colorectal cancer (CRC) is a high-incidence tumor worldwide. Targeted therapy and immune therapy significantly improve survival than before. It was reported in 2018 ASCO GI that circulating tumor cells is capable of detecting CRC patients in early stage. CIMP-H associates higher risk of advanced metachronous lesion and genetic profile of polyps could go beyond size and number in the prediction of advanced metachronous lesions. Regarding to targeted therapy, for metastatic colorectal cancer patients previously treated with fluoropyrimidine, oxaliplatin and irinotecan, sequential treatment with regorafenib (R) followed by cetuximab (C) ± irinotecan (R-C arm) is preferred than reverse sequence (C-R arm), especially in OS. In filed of immune therapy, nivolumab+ ipilimumab combination in patients with DNA mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) mCRC patients would demonstrate enhanced clinical benefit and manageable safety.
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ASCO GI; Colorectal neoplasms; Screening; Targeted therapy; Immune therapy
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Targeted Therapy
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Uncertainty exists about whether elderly patients benefit to the same extent as younger patients from the chemotherapy for colorectal cancer. Patients older than 75 years of age are usually excluded from metastatic colorectal cancer randomized studies. Some subset analyses with comparison of younger and elderly patients from these pooled data revealed the significance of the chemotherapy for elderly colorectal cancer patients. This article introduces the review of these subset analyses and JCOG1018 trial which is on-going study to clarify the efficacy of oxaliplatin combination first line chemotherapy for elderly metastatic colorectal cancer patients.
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