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terrible! Non-small cell lung cancer can transform to small cell lung cancer! Such patients need special attention.

Non-small cell lung cancer can transform to small cell lung cancer! Lung cancer is divided into non-small cell lung cancer and small cell lung cancer. Small cell lung cancer has the characteristics of difficult treatment and rapid development.

After the diagnosis of lung cancer, the first thing to do is to confirm the specific pathological type. The treatment and prognosis of different pathological types of lung cancer vary greatly.

Lung cancer is divided into non-small cell lung cancer and small cell lung cancer. Among them, non-small cell lung cancer accounts for more than 80%, including adenocarcinoma, squamous cell carcinoma and large cell carcinoma.

The number of small cell lung cancer patients is relatively small, but compared with non-small cell lung cancer, its rapid progress, limited treatment options, and short survival period, even today with the rise of targeted and immunotherapy, it can be regarded as a “nightmare”.

Patients diagnosed with non-small cell lung cancer may secretly fluke, especially patients taking targeted drugs, although unfortunately they have cancer, but luckily it is a relatively good type of pathology.

However, do you know that the boundary between non-small cell lung cancer and small cell lung cancer is not so absolute, and even among patients taking targeted drugs, non-small cell lung cancer may also transform into small cell lung cancer! Also known as “transforming small cell lung cancer” Cell lung cancer”.

Transformational SCLC (small cell lung cancer) is similar to classic SCLC in terms of pathological morphology, molecular characteristics, clinical manifestations, and drug sensitivity, but it cannot be completely classified as classic SCLC, and may be classified as a new type. The SCLC subtype.

▌How does the conversion happen?

In recent years, the treatment of non-small cell lung cancer has been dominated by EGFR inhibitor targeted therapy, but the problem of drug resistance has not been circumvented! 

Almost all patients receiving EGFR targeted drug therapy will eventually inevitably develop drug resistance, among which drug resistance There are many different mechanisms, most of which are other gene mutations.

However, there are about 5%-14% of patients who cannot detect drug resistance mutations after drug resistance. After struggling to find the cause, they found that the pathological form was transformed from non-small cell lung cancer to small cell lung cancer!

Although most of the transformed tumor tissues still carry EGFR gene mutations, the EGFR gene no longer leads the production of protein, so the targeted drugs that act on the protein lose their effect.

Why does a subtype change occur after targeted therapy drug resistance? There is no accurate statement yet.

• Some people believe that a small amount of small cell lung cancer is mixed with primary adenocarcinoma. After multiple treatments and disease development, small cell lung cancer has transformed into a dominant clone;
• It is also believed that small cell lung cancer and adenocarcinoma are derived from pluripotent stem cells that share EGFR mutations, or at least part of small cell lung cancers are derived from adenocarcinomas that carry EGFR mutations and thyroid transcription factor-1 positive.

The author believes that small cell lung cancer progresses rapidly and has a short survival time, with a median survival time of about half a year; and follow-up studies have shown that the median time for small cell lung cancer transformation to occur is 17.8 months. Considering time, individuals are more inclined to the transformation of pathological types! Of course, this requires more in-depth research to clarify.

▌Transformation occurred one and a half years after diagnosis, and the prognosis was poor

A retrospective study published by Nicolas Marcoux on JCO showed that about 3% to 10% of EGFR-mutant NSCLC will transform into small cell lung cancer.

The study retrospectively analyzed 67 small cell lung cancer patients with EGFR mutations, of which 58 patients had non-small cell lung cancer at the initial diagnosis of lung cancer and received one or more EGFR-targeted therapies before the transformation The remaining 9 cases were new small cell lung cancer or mixed histological types.

research shows:

·The median time for transformation of small cell lung cancer is 17.8 months (95% CI: 14.3-26.2);

·The median overall survival after diagnosis of lung cancer is 31.5 months, while the median overall survival after transformation of small cell lung cancer is only 10.9 months.

After conversion, patients had a high response rate to chemotherapy (platinum-etoposide and taxanes), but 17 patients who received immunotherapy did not respond to treatment.

In addition, most of the currently reported patients with small cell lung cancer transformation are non-smokers, and this type of patients develops small cell lung cancer transformation later.

▌This type of patient needs special attention!

Although it is rare for non-small cell lung cancer to transform into small cell lung cancer after targeted therapy, it is necessary to perform a second pathological biopsy to see if it transforms into large and newly emerging lesions after targeted drug resistance. Small Cell Lung Cancer.

Lee et al. found that patients with lung adenocarcinoma with simultaneous mutations of RB1 and TP53 are 42.8 times more likely to undergo pathological transformation into small cell lung cancer during treatment.

Lee studied 21 patients with advanced lung adenocarcinoma who had EGFR mutations and transformed into small cell carcinoma after treatment, and performed genetic testing on 4 patients with different lesions at different stages. The study found that the gene differentiation of small cells and adenocarcinoma cells occurred long before the first targeted drug therapy; these patients had both RB1 and TP53 gene inactivation at the same time when they were still adenocarcinoma.

The probability of simultaneous inactivation of RB1 and TP53 in lung adenocarcinoma is 5%, which is similar to the probability of transforming to small cell lung cancer after targeted therapy.

The researchers then compared the failures of RB and TP53 in 210 lung cancer tissues. Among the 17 patients with transformation and 58 patients without transformation, the number of patients with inactivation of these two genes in the initial adenocarcinoma state were 14 and respectively. 2. Except for the inactivation of these two genes, there was no significant difference between the small cell and non-transfected small cell comparison groups.

Therefore, patients with EGFR, TP53, and RB1 mutations are more likely to develop small cell lung cancer transformation during treatment than other EGFR mutation patients, and it is necessary to highly suspect small cell lung cancer transformation when drug resistance occurs during treatment.

▌How to treat small cell lung cancer after transformation?

For patients whose non-small cell lung cancer is transformed into small cell lung cancer through EGFR-targeted drug resistance, most of them are currently treated individually based on the patient’s own conditions.

Although most of the transformed tumor tissues still carry EGFR gene mutations, the EGFR gene no longer leads the production of protein, so the targeted drugs acting on the protein lose their effectiveness.

·For the standard treatment of extensive-stage SCLC, the first-line treatment is mainly platinum-containing dual-agent chemotherapy, mainly etoposide + cisplatin/carboplatin, irinotecan + cisplatin/carboplatin;

The second-line treatment is topotecan;

In addition, targeted therapy and immunotherapy are also available. On March 18, 2019, the US FDA approved atelizumab in combination with carboplatin and etoposide for the first-line treatment of patients with extensive-stage small cell lung cancer.

For the treatment of transforming small cell lung cancer, there are also relevant content updates at the recent 2021 CSCO guidelines conference.

Although the incidence of non-small cell lung cancer transforming into small cell lung cancer is very low, who can guarantee that it will not happen?

Therefore, for high-risk groups of small cell lung cancer, more frequent monitoring is needed, and the tissues should be retaken for pathology in the early stage of progression. When there are difficulties in the treatment process and the effect of multiple dressing changes is not good, a needle biopsy is needed in time to see if there is any conversion of non-small cell lung cancer to small cell lung cancer, so that the treatment plan can be adjusted in time.

(source:internet, reference only)

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