The HERACLES-A and MyPathway studies have shown benefit in a small number of patients with the use of combination trastuzumab-lapatinib and trastuzumab-pertuzumab, respectively(9, 10). Testing for HER2 expression is currently a practice in the management of colorectal cancer. However, the positive rate of HER2 in colorectal cancer is not consistent in domestic and foreign literature reports. Our study demonstrated a 20.6% rate of HER2 expression. PET/CT is a molecular imaging technique widely used in the diagnosis and staging of malignant tumors. Our results showed that the SUVmax in colorectal cancer was significantly higher when HER2 was expressed than when not expressed. Besides, SUVmax and the PFS of patients have significantly statistical differences. To our knowledge, this was the first study to analyze the association between HER2 expression and predictive value of 18F-FDG PET/CT parameters in colorectal cancer patients.
Our data also demonstrated that HER2 expression is more common in big primary tumor size than in small size. This finding is similar to the findings of previous studies(19). In addition, big primary tumor had significantly higher 18F-FDG uptake than did small primary tumor, partly explaining why patients with HER2 expression had a high SUVmax. But the reasons for this selective high rate of HER2 expression in big primary tumor sizes remain unclear. Multivariate analysis revealed that both the SUVmax of the primary tumor and the tumor size correlated significantly with HER2 expression. We further categorized patients into groups based on their potential for being HER2-positive: high-potential, moderate-potential, and low-potential. HER2 was expressed in 40.7% of the high-potential group while in 13.2% of the low-potential group, implying that anti-HER2 therapies are not effective for patients with a low potential of being HER2-positive. For these reasons, noninvasive methods, such as molecular imaging, for predicting HER2 status have great clinical relevance. In our study, SUVmax has the independently potential to evaluate the HER2 status in colorectal carcinoma with metastatic lesions. Meanwhile, SUVmax united to the sizes of the primary tumors can also precisely forecast the HER2 expression in colorectal cancer.
The “Trastuzumab for Gastric Cancer” trial on metastatic gastric cancer demonstrated a significant overall survival benefit when trastuzumab was combined with chemotherapy(20). HER2 status is routinely used to predict the efficacy of anti-HER2 therapies. Actually, the role of HER2 as a prognostic factor in colorectal cancer had been controversial(21). the HERACLES-A and MyPathway studies demonstrated that patients with HER2 amplification did not derive a survival benefit from chemoradiation therapy whereas patients without HER2 amplification derived a statistically significant survival benefit. Some studies failed to find an association with prognosis(22, 23), whereas others found a direct correlation between HER2 expression or amplification and poor survival(24, 25). In our study, there’s no significantly statistical difference between HER2 expression and the PFS of patients, we could attribute this result to the lack of anti-HER2 therapies on the selected patients. In a future study, we intend to collect specific anti-HER2 therapy cases to elucidate the correlations between HER2 expression, progression free survival, and the 18F-FDG uptake of anti-HER2 therapy patients. The present data shows that patients with higher SUVmax had longer median PFS than ones with lower SUVmax. This result is not similar to many studies(26, 27). The reasons of such a result are not very clear. Data bias cannot be excluded. Another reason we speculated is that the higher FDG uptake may indicate the more sensitive therapeutic effect. But it needs more correlational studies to prove this assumption.
This study was partly limited by its retrospective design and no HER2-targeted molecular therapies. Although PET/CT may have a moderate diagnostic performance, as we all know, it cannot replace conventional methods in the clinical setting. Nonetheless, our results may be relevant for the development of noninvasive strategies to predict prognosis and HER2 expression in colorectal cancer patients. Advances in PET radiotracers may increase the sensitivity and specificity of this technique and enable full molecular assessment of colorectal cancer.