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Locally advanced rectal cancer (LARC) remains a medical challenge. Reliable biomarkers to predict which patients will significantly respond to neoadjuvant chemoradiotherapy (nCRT) have not been identified. We evaluated baseline genomic and transcriptomic features to detect differences that may help predict response to nCRT. Eligible LARC patients received nCRT (3D-LCRT 50.4 Gy plus capecitabine 825 mg/m2/bid), preceded by three cycles of CAPOX in high systemic-relapse risk tumors, and subsequent surgery. Frozen tumor biopsies at diagnosis were sequenced using a colorectal cancer panel. Transcriptomic data was used for pathway and cell deconvolution inferential algorithms, coupled with immunohistochemical validation. Clinical and molecular data were analyzed according to nCRT outcome. Pathways related to DNA repair and proliferation (p < 0.005), and co-occurrence of RAS and TP53 mutations (p = 0.001) were associated with poor response. Enrichment of expression signatures related to enhanced immune response, particularly B cells and interferon signaling (p < 0.005), was detected in good responders. Immunohistochemical analysis of CD20+ cells validated the association of good response with B cell infiltration (p = 0.047). Findings indicate that the presence of B cells is associated with successful tumor regression following nCRT in LARC. The prevalence of simultaneous RAS and TP53 mutations along with a proficient DNA repair system that may counteract chemoradio-induced DNA damage was associated with poor response.

Highlights High-risk HPV infection is less frequently detected in HIV-positive non-metastatic ASCC compared with HIV-negative cases. Mutational profile identified in the non-metastatic ASCC cohort revealed expected similarities with metastatic ASCC. High PD-L1 expression levels are associated with high CD3 and CD8 TIL density, complete response to treatment, and good survival outcome of ASCC patients. PD-L1 is a reliable predictive and prognostic biomarker that allows the stratification in low- vs. high-risk ASCC patients at their initial therapeutic approach.

Background: Our previous study demonstrated that liver metastases (LM) were the negative predictive and prognostic factor in EGFR-mutant NSCLC patients (Pts) treated with EGFR-TKIs, suggesting that additional treatment is warranted. Recently, several studies reported that local therapy could significantly improve progression-free survival (PFS) in NSCLC Pts with oligometastatic or oligoprogressive disease. This study aimed to investigate whether addition of local therapy to EGFR-TKIs could provide survival benefit in EGFR-mutant NSCLC Pts with oligometastatic or oligoprogressive LM. Methods: Pts with EGFR-mutant NSCLC and LM were included. Oligometastatic LM was defined as <5 sites in liver without extrahepatic metastases at initial diagnosis. Oligoprogressive LM was defined as <5 sites in liver without extrahepatic metastases during TKIs therapy. For oligoprogressive cohort, PFS1 was calculated from time of initiation of TKI therapy to first RECIST 1.1 defined progress disease (PD) or death. PFS2 was calculated from time of initiation of TKI therapy to off-TKI PD. Results: 289 Pts with LM were enrolled (55 with oligometastatic LM and 63 with oligoprogressive LM). In oligometastatic cohort, 18 Pts received EGFR-TKIs (E) and 21 Pts received TKIs plus local therapy (E + LT) as firstline treatment. Median PFS was significantly longer in E + LT group than in E group (12.2 vs. 7.9 m, P = 0.030). Median OS was numerically longer in E + LT group than in E group (31.7 vs. 21.3 m, P = 0.102). In oligoprogressive cohort, 19 Pts received continuation of TKIs plus local therapy (cE + LT) and 22 Pts received switch therapy (ST). Median PFS1 was comparable. Median PFS2 was dramatically longer in cE + LT group than in ST group (13.9 vs. 8.8 m, P = 0.050). Median OS was marginally significantly longer in cE + LT group than in ST group (24.7 vs. 15.7 m, P = 0.085). Multivariate analysis revealed that addition of local therapy was independently associated with prolonged PFS and OS in Pts with oligometastatic LM. Conclusions: The current study indicated that EGFR-TKIs plus local therapy demonstrated the prolonged survival benefit than TKIs alone in EGFR-mutant NSCLC Pts with oligometastatic or oligoprogressive LM.