Patients with early-stage NSCLC treated with SBRT taking ARB antihypertensive drugs can extend survival to 96.7 months

Stereotactic radiation therapy (SBRT) has become an important curative treatment for early-stage non-small cell lung cancer (NSCLC), especially in patients who are inoperable or refuse surgery
.
Despite this, approximately 40% of patients develop relapse or distant metastases
.
Therefore, scientists are looking for factors that drive early NSCLC tumor metastasis in hopes of finding treatments
that reduce the risk of distant recurrence.

Transforming growth factor-β (TGF-β) is a multidirectional, pleiotropic cytokine that regulates cell multiplication, differentiation, and apoptosis
in an autocrine or paracrine manner through receptor signaling pathways on the cell surface.
It has an important regulatory effect
on the synthesis of extracellular matrix, wound repair, immune function, etc.
Blocking TGF-β is thought to improve local and distant cancer control
by acting on tumor cells, the microenvironment, and anti-tumor immune responses.
Anti-TGF-β therapy has yielded some encouraging results
in early clinical studies.

Angiotensin-II receptor blockers (ARBs) are commonly used antihypertensive drugs that indirectly inhibit TGF-β signaling
.
Studies have shown that patients with advanced NSCLC who receive platinum-based chemotherapy have improved
median survival when they take ARB at the same time.
In addition, the inclusion of ARB in neoadjuvant therapy has shown encouraging results
.
A recent study published in the journal Cancer Biol Ther investigated patients with early-stage lung cancer who received SBRT taking ARB at the same time compared to those who did not take it , whether it shows an improvement
in overall survival (OS) or relapse-free survival (RFS).

In the study, researchers conducted a retrospective analysis of 272 patients treated with early-stage lung cancer with SBRT between 2009 and 2018, with patient data extracted from electronic medical records
。 The OS and RFS
were evaluated using the Kaplan-Meier method.
Use the Logrank test to compare survival rates
between groups.
Risk ratios (HRs)
are estimated by univariate and multivariate Cox proportional hazards regression models.

The results showed that of the 247 patients, 24 (10%) took ARB
during radiotherapy.
There was no difference
in the mean age, median tumor diameter, or median bioeffective dose of patients taking ARB.
Patients taking ARB showed longer OS (ARB = 96.
7 months; No ARBs = 43.
3 months; HR = 0.
25 [95% CI: 0.
10 to 0.
62, P=.
003]) and RFS (median RFS, ARB=64.
3 months; No ARB = 35.
1 months; HR=0.
26 [95% CI: 0.
10 to 0.
63, P=.
003]).

However, these effects were not seen in patients taking angiotensin-converting enzyme inhibitors (ACEI) or statins.

The use of ARB when treated with SBRT for early-stage lung cancer may increase OS and RFS, but ACEI has not shown the same effect
。

ACE inhibitors and ARBs have obtained a lot of clinical evidence as first-line drugs for the treatment of hypertension, and are recommended as first-line antihypertensive drugs
in domestic and foreign guidelines.
ACEI and ARB are equally effective in reducing blood pressure, but ARB has fewer
side effects than ACEI.
There are many varieties of ARB drugs, often named after sartan, and the current sartan drugs include valsartan, losartan, irbesartan, telmisartan, candesartan, olmesartan and alisartan, these 7 sartan drugs can be safe and effective to lower blood pressure
.

In summary, the prognosis of patients with early-stage NSCLC treated with SBRT may be improved
by the addition of ARB therapy.
Importantly, the safety of ARB is well studied, well tolerated, cost-effective, and offers the potential to
improve survival.
In the future, this finding should be validated in larger retrospective and prospective studies to demonstrate its reproducibility and universality
.

Original provenance

Maloney LT, Latour E, Chen Y, Rice D, Grossblatt-Wait A, Nabavizadeh N, Thomas CR, Young KH, Walker JM, Holland J, Grossberg AJ.
Angiotensin receptor blockade and stereotactic body radiation therapy for early stage lung cancer ARB & SBRT for early stage lung cancer.
Cancer Biol Ther.
2022 Dec 31; 23(1):1-8.
doi: 10.
1080/15384047.
2022.
2126250.
PMID: 36201632; PMCID: PMC9542943.