Reproduced From Oncology Frontier |
| Giulia Veronesi, MD Division of Thoracic Surgery Director, Lung Cancer Early Detection and Prevention Unit European Institute of Oncology Milan, Italy |
Oncology Frontier(肿瘤瞭望): Can biomarkers be of help in the diagnosis of small nodules?
Dr. Veronesi: I am a thoracic surgeon, and I have dedicated many years to the screening of lung cancer.
As you know, screening has been validated as a tool with low-dose CT scan for lung cancer, but one of the drawbacks is the high rate of indeterminate nodules in screening.
So it's important to have tools to better characterize these nodules, and the research of molecular markers is very important. A number of literatures have been analyzed.
Immunity Component biomarkers
There are two categories of circulating markers, which are very good phases of validation. One is an immunity component of the complement in this molecule, the C4D, which has been detected by a group of Spanish researchers. It is a good tool， but it is already validated in the screening court with the main limitation of low sensitivity. So, it is not one of the most promising.
Another tool is the research of autoantibodies, against abnormal partings in the surface of cancer cells. There is a literature of seven autoantibodies that is already put on the market, yet the detection rate is very low, around 40% sensitivity, while the specificity is very high.
Micro-RNAs biomarkers
The other most promising markers are a group of molecular circulating micro-RNAs， which we have worked on molecules in the serum.
We have identified a signature of 13 micro-RNAs, detected in a screening court, validated in retrospect in a second screening court, and now there is an ongoing study, a perspective screening trial, multicenter, with the main objective of validating the prospect of this type of signature. The accuracy is around 80%, and we perform a CT scan and a blood sample with a micro-RNA analysis.
Micro-RNAs biomarker in the pipeline
The objective of this new study, that involves 7,000 individuals in Italy, is to obtain a molecular marker able to reduce the need of a CT scan, thus improving the effectiveness of screening, because CT scans have drawbacks such as exposure to radiation. So, this can be a first line screening tool that can be of help in implementing screening on a large scale population.
I think the final validation will be in a prospective randomized trial, so probably we will need an additional five or six years to obtain something that can be used in the clinic.
Other markers include transcutaneous bioconductance, sputum cell 3 d, breath test etc.
How to improve diagnostic accuracy of small pulmonary nodules?
Dr. Veronesi: In our screening court，we had a nice sensitivity to detect lung cancer，and a specificity which was very good compared to other studies. However, not optimal in the sense that we had around 14% of nodules that had received surgical action that were benign.
When compared to, for example, what has been obtained in other screening courts like NLST (the national lung screening trial), it is a good result because NLST had more than 20-25% of false positives at surgery.
But our objective is to reduce the false positive rate to the minimum. What we have found in our ten year annual screening， in which it is obviously important to have the diagnostic algorithm that takes into consideration different parameters like VDT (volume doubling time) of nodules, the CT, PET result, the size, the shape of the nodules, and so on.
In our court, we take into consideration all these parameters among precise diagnostic algorithms. We can see that this false positive detection rate was reduced over the years with increased experience, so it's also important that any positive case is discussed in an inter- and multi-disciplinary team meeting to obtain the maximum accuracy for these nodules.
What is the optimal management strategy for the malignant solitary pulmonary nodule (SPN)？
Dr. Veronesi: So far the surgical resection with patients fit to receive the surgery is the standard.
We know that minimally invasive approaches are nowadays more diffused, compared to the past in which thoracotomy was performed.
Now we always perform video-thoracoscopic approach or robotic approach, and the objective is to reduce the invasiveness of surgery and increase the quality of life of patients.
There is another trend, which is the reduction of the extension of resection.
In the past, the standard approach was a lobectomy with radical lymph node dissection, and we could see in our research that as the cancers have very small nodule sizes in very early stages, in most of them it's possible to perform a lung sparing sublobar resection, and in most cases an anatomic segmentectomy is the good adequate oncological procedure.
So, most of our work cases are treated with minimally-invasive, so mainly robotic, segmentectomy.
For those cases that are larger than 2 centimeters, or very aggressive tumors, the standard anatomical lobectomy is performed, mainly with minimally invasive access.
The new point for the future is to evaluate the potential of stereotactic radiotherapy for various small nodules， both in the case of primary lesions, but in particular for lesions that are multifocal, second primary, or that have already received a lobectomy.
So far, radiotherapy has been proposed as a good alternative to surgery for patients that are unfit for surgery. Now we are going to evaluate it for patients who can be treated with surgery, but in which surgery is correlated with higher mortality compared to radiotherapy.
So, in the future our objective will be to screen cancer, to have a noninvasive diagnosis and a noninvasive treatment.
Reference：
[ELCC 2015]生物标志物是否有助于肺小结节诊断--Giulia Veronesi 医生访谈
2015/4/28 肿瘤瞭望 © Video微信公众号
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