Neoadjuvant immunotherapy (nIT) is a rapidly emerging paradigm for advanced resectable non-small cell lung cancer (NSCLC). The objectives of this PRISMA/MOOSE/PICOD-guided systematic review and meta-analysis were (1) to assess the safety and efficacy of nIT, (2) to compare the safety and efficacy of neoadjuvant chemoimmunotherapy (nCIT) versus chemotherapy alone (nCT), and (3) to explore predictors of pathologic response with nIT and their association with outcomes.
Eligibility was resectable stage I-III NSCLC and the receipt of programmed death-1/programmed cell death ligand-1 (PD-L1)/cytotoxic T-lymphocyte-associated antigen-4 inhibitors before resection; other forms and modalities of neoadjuvant and/or adjuvant therapies were allowed. For statistical analysis, the Mantel-Haenszel fixed-effect or random-effect model was used, depending on the heterogeneity (I2 ).
Sixty-six articles met the criteria (eight randomized studies, 39 prospective nonrandomized studies, and 19 retrospective studies). The pooled pathologic complete response (pCR) rate was 28.1%. The estimated grade ≥3 toxicity rate was 18.0%. Compared with nCT, nCIT achieved higher rates of pCR (odds ratio [OR], 7.63; 95% confidence interval [CI], 4.49-12.97; p < .001), progression-free survival (PFS) (hazard ratio [HR] 0.51; 95% CI, 0.38-0.67; p < .001), and overall survival (OS) (HR, 0.51; 95% CI, 0.36-0.74; p = .0003) but yielded similar toxicity rates (OR, 1.01; 95% CI, 0.67-1.52; p = .97). The results remained robust on sensitivity analysis when all retrospective publications were removed. pCR was associated with improved PFS (HR, 0.25; 0.15-0.43; p < .001) and OS (HR, 0.26; 95% CI, 0.10-0.67; p = .005). PD-L1 expressors (≥1%) were more likely to achieve a pCR (OR, 2.93; 95% CI, 1.22-7.03; p = .02).
In patients with advanced resectable NSCLC, neoadjuvant immunotherapy was safe and efficacious. nCIT improved pathologic response rates and PFS/OS over nCT, particularly in patients who had tumors that expressed PD-L1, without increasing toxicities.
This meta-analysis of 66 studies showed that neoadjuvant immunotherapy for advanced resectable non-small cell lung cancer is safe and efficacious. Compared with chemotherapy alone, chemoimmunotherapy improved pathologic response rates and survival, particularly for patients who had tumors that expressed programmed cell death ligand-1, without increasing toxicities.

To date, there is no approved biomarker for predicting pathological response in neoadjuvant programmed cell death (ligand) 1 (PD-(L)1) blockades treated early-stage non-small cell lung cancer (NSCLC). Databases including PubMed, Embase, ClinicalTrials.gov, and Conference abstracts were searched for clinical trials of neoadjuvant PD-1/PD-L1 blockades for resectable NSCLC. Data regarding major pathological response (MPR), pathological complete response (pCR) in patients with high/low pretreatment PD-L1 expression, and tumor mutation burden (TMB) were synthesized using fixed-model meta-analysis and evaluated by odds ratio with 95 % confidence interval. This analysis included 10 studies involving 461 NSCLC patients. Compared with PD-L1 expression <1%, PD-L1 expression ≥1% is associated with a higher rate of MPR and pCR. High-TMB associated with MPR and pCR. Similar findings were observed in subgroup analyses despite mono-PD-1/PD-L1 blockade or their combination with chemotherapy. Notably, 50 % as the cutoff value for PD-L1 expression demonstrated better prediction efficacy for MPR than that of 1%.

To determine the overall performance of contrast-enhanced ultrasound (CEUS) in differentiating between benign and malignant breast lesions and in predicting the pathologic response to neoadjuvant chemotherapy (NAC) in patients with breast cancer (BC).
Articles published up to April 2019 were systematically searched in Medline, Web of Science, and China National Knowledge Infrastructure. The sensitivities and specificities across studies, the calculations of positive and negative likelihood ratios (LR+ and LR-), diagnostic odds ratio (OR), and constructed summary receiver operating characteristic curves were determined. Methodologic quality was assessed using the QUADAS (Quality Assessment of Diagnostic Accuracy Studies) tool. Subgroup analyses and metaregression were performed on prespecified study-level characteristics.
Fifty-one studies involving 4875 patients with 5246 breast lesions and 10 studies involving 462 patients with BC receiving NAC were included. Methodologic quality was relatively high, and no publication bias was detected. The overall sensitivity, specificity, diagnostic OR, LR+, and LR- for CEUS were 0.88 (95% confidence interval [CI], 0.86-0.89), 0.82 (95% CI, 0.80-0.83), 30.55 (95% CI, 21.40-43.62), 4.29 (95% CI, 3.51-5.25), and 0.16 (95% CI, 0.13-0.21), respectively, showing statistical heterogeneity. Multivariable metaregression analysis showed contrast mode to be the most significant source of heterogeneity. The overall sensitivity, specificity, LR+, LR, and diagnostic OR of CEUS imaging in predicting the overall pathologic response to NAC in patients with BC were 0.89 (95% CI, 0.83-0.93), 0.83 (95% CI, 0.78-0.88), 4.49 (95% CI, 3.04-6.62), 0.16 (95% CI, 0.10-0.24,), and 32.21 (95% CI, 16.74-62.01), respectively, showing mild heterogeneity.
Our data confirmed the excellent performance of breast CEUS in differentiating between benign and malignant breast lesions as well as pathologic response prediction in patients with BC receiving NAC.

The purpose of this study was to assess the use of apparent diffusion coefficient (ADC) during DWI for predicting complete pathologic response of rectal cancer after neoadjuvant therapy.
A systematic review of available literature was conducted to retrieve studies focused on the identification of complete pathologic response of locally advanced rectal cancer after neoadjuvant chemoradiation, through the assessment of ADC evaluated before, after, or both before and after treatment, as well as in terms of the difference between pretreatment and posttreatment ADC. Pooled mean pretreatment ADC, posttreatment ADC, and Δ-ADC (calculated as posttreatment ADC minus pretreatment ADC divided by pretreatment ADC and multiplied by 100) in complete responders versus incomplete responders were calculated. For each parameter, we also pooled sensitivity and specificity and calculated the area under the summary ROC curve.
We found 10 prospective and eight retrospective studies. Overall, pathologic complete response was observed in 22.2% of patients. Pooled mean pretreatment ADC in complete responders was 0.84 × 10-3 mm2/s versus 0.89 × 10-3 mm2/s in incomplete responders (p = 0.33). Posttreatment ADC values were 1.51 × 10-3 mm2/s and 1.29 × 10-3 mm2/s, in complete and incomplete responders, respectively (p = 0.00001). The Δ-ADC percentages were also significantly higher in complete responders than in incomplete responders (59.7% vs 29.7%, respectively, p = 0.016). Pooled sensitivity, specificity, and AUC were 0.743, 0.755, and 0.841 for pretreatment ADC; 0.800, 0.737, and 0.782 for posttreatment ADC; and 0.832, 0.806, and 0.895 for Δ-ADC.
Use of ADC during DWI is a promising technique for assessment of results of neoadjuvant treatment of rectal cancer.