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A narrative review of combined stereotactic ablative radiotherapy and immunotherapy in metastatic non-small cell lung cancer.

ABSTRACT: Immune checkpoint inhibitors (ICIs) have significantly improved overall survival (OS) in metastatic non-small cell lung cancer (m-NSCLC). However, not all patients with m-NSCLC benefit from ICIs, and resistance to ICIs is an emerging challenge. The tumour microenvironment (TME) is immunosuppressive, and provides a myriad of mechanisms to facilitate escape of cancer cells from immune surveillance. The TME may also dampen the response to ICIs by inhibiting T cell effector responses. The poor prognosis of m-NSCLC has led to investigation of ICIs combined with other treatments with the intention of modulating the TME and sensitizing tumours to the effects of ICIs. Stereotactic ablative radiotherapy (SABR) in combination with ICIs is an area of intense interest. SABR is thought to evoke a pro-immunogenic response in the TME, with the capacity to turn a "cold", unresponsive tumour to "hot" and receptive to ICI. In addition to improved local response, SABR is postulated to produce a heightened systemic immune response when compared to conventional radiotherapy (RT). Preclinical studies have demonstrated a synergistic effect of SABR + ICIs, and clinical studies in m-NSCLC showed safety and promising efficacy compared to systemic therapies alone. To optimize ICI + SABR, ICI choice, combinations, dosing and length of treatment, as well as sequencing of ICI + SABR all require further investigation. Appropriate sequencing may depend on the ICI(s) being utilized, with differing sites of metastases possibly eliciting differing immune responses. Single versus multisite radiation is controversial, whilst effects of irradiated tumour volume and nodal irradiation are increasingly recognized. Taken together, there is strong preclinical and biological rationale, with emerging clinical evidence, supporting the strategy of combining SABR + ICIs in m-NSCLC.

SUBMITTER: Akanda ZZ

PROVIDER: S-EPMC8264312 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The incidence of early-stage non-small cell lung cancer (NSCLC) among the elderly is expected to rise dramatically owing to demographic trends and increased computed tomographic screening. However, to our knowledge, no modern trials have compared the most common treatments for NSCLC.To determine clinical characteristics and survival outcomes associated with the 3 most commonly used definitive therapies for early-stage NSCLC in the elderly.The Surveillance, Epidemiology, and End Results database linked to Medicare was used to determine the baseline characteristics and outcomes of 9093 patients with early-stage, node-negative NSCLC who underwent definitive treatment consisting of lobectomy, sublobar resection, or stereotactic ablative radiotherapy (SABR) from January 1, 2003, through December 31, 2009.Overall and lung cancer-specific survival were compared using Medicare claims through December 31, 2012. We used proportional hazards regression and propensity score matching to adjust outcomes for key patient, tumor, and practice environment factors.The median age was 75 years, and treatment distribution was 79.3% for lobectomy, 16.5% for sublobar resection, and 4.2% for SABR. Unadjusted 90-day mortality was highest for lobectomy (4.0%) followed by sublobar resection (3.7%; P = .79) and SABR (1.3%; P = .008). At 3 years, unadjusted mortality was lowest for lobectomy (25.0%), followed by sublobar resection (35.3%; P < .001) and SABR (45.1%; P < .001). Proportional hazards regression demonstrated that sublobar resection was associated with worse overall survival (adjusted hazard ratio [AHR], 1.32 [95% CI, 1.20-1.44]; P < .001) and lung cancer-specific survival (AHR, 1.50 [95% CI, 1.29-1.75]; P < .001) compared with lobectomy. Propensity score-matching analysis reiterated these findings for overall survival (AHR, 1.36 [95% CI, 1.17-1.58]; P < .001) and lung cancer-specific survival (AHR, 1.46 [95% CI, 1.13-1.90]; P = .004). In proportional hazards regression, SABR was associated with better overall survival than lobectomy in the first 6 months after diagnosis (AHR, 0.45 [95% CI, 0.27-0.75]; P < .001) but worse survival thereafter (AHR, 1.66 [95% CI, 1.39-1.99]; P < .001). Propensity score-matching analysis of well-matched SABR and lobectomy cohorts demonstrated similar overall survival in both groups (AHR, 1.01 [95% CI, 0.74-1.38]; P = .94).Lobectomy was associated with better outcomes than sublobar resection in elderly patients with early-stage NSCLC. Propensity score matching suggests that SABR may be a good option among patients with very advanced age and multiple comorbidities.

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A narrative review of combined stereotactic ablative radiotherapy and immunotherapy in metastatic non-small cell lung cancer.

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