Response rate and diagnostic accuracy of early PET-CT during neo-adjuvant therapies in oesophageal adenocarcinoma: a systematic review and meta-analysis.


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Clare Hannon, Elizabeth Smyth, Jaqueline Jeffries, Bernadette Coles, Kevin Bradley, Kieran Foley

Abstract

Background

Neo-adjuvant therapy prior to oesophagectomy is standard of care in potentially resectable, locally advanced oesophageal adenocarcinoma despite less than 25% of patients have a clinical meaningful response. Early response assessment using positron emission tomography (PET) imaging has been explored to guide management of these patients. We performed a systematic review and meta-analysis to synthesise the evidence detailing early response rate and diagnostic accuracy of early PET-CT assessment.

Method

We systematically searched several databases (e.g. MEDLINE, Embase, Cochrane Library, CINAHL). Studies recruiting mixed cohorts of histological cell type, tumour location, and repeat PET-CT assessment after more than one cycle of neo-adjuvant therapy were excluded. The reference standard was pathological response, defined using either Becker or Mandard classifications. The primary outcome was metabolic response rate after one cycle of neo-adjuvant therapy defined by a reduction in maximum standardised uptake value (SUVmax) of 35%. Secondary outcome was diagnostic accuracy of treatment response prediction, defined as the sensitivity and specificity of early PET-CT using this threshold. The quality of evidence was also assessed. Random-effects meta-analysis was used to pool response rate and diagnostic accuracy data. This study is registered with PROSPERO, registration number CRD42019147034.

Results

In total, 1341 articles were screened, and 6 studies were eligible for analysis. These studies reported data for 518 patients (aged 27-78 years; of which 452 [87.3%] were male) between 2005 and 2020. The pooled sensitivity of early metabolic response to predict pathological response was 77.2% (95% CI 53.2%-100%). There was significant heterogeneity between studies (I2 = 80.6% (95% CI 38.9%-93.8%), p=0.006). The pooled specificity was 75.0% (95% CI 68.2%-82.5%), however no significant heterogeneity between studies existed (I2 = 0.0% (95% CI 0.0%-67.4%), p=0.73).

Conclusion

High-quality evidence is lacking, and few studies met the inclusion criteria of this systematic review. The sensitivity of PET using a SUVmax reduction threshold of 35% was suboptimal and varied widely. However, specificity was consistent across studies with a pooled value of 75.0%, suggesting early PET assessment is a more consistent predictor of treatment resistance than of pathological response. Further research is required to define optimal PET-guided treatment decisions in oesophageal adenocarcinoma.

Impact statement