16 research outputs found

    Prognostic and predictive value of Immunoscore in stage III colorectal cancer: pooled analysis of 2,608 cases from the SCOT and IDEA-HORG studies

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    Purpose Immunoscore (IS) is prognostic in stage III colorectal cancer (CRC) and may predict benefit of duration (6 v 3 months) of adjuvant infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy. We sought to determine IS prognostic and predictive value in stage-III CRC treated with adjuvant FOLFOX or oral capecitabine and infusional oxaliplatin (CAPOX) in the SCOT and IDEA-HORG trials. Methods Three thousand sixty-one cases had tumor samples, of which 2,643 (1,792 CAPOX) were eligible for IS testing. Predefined cutoffs (IS-Low and IS-High) were used to classify cases into two groups for analysis of disease-free survival (3-year DFS) and multivariable-adjusted hazard ratios (mvHRs) by Cox regression. Results IS was determined in 2,608 (99.5%) eligible cases, with 877 (33.7%) samples classified as IS-Low. IS-Low tumors were more commonly high-risk (T4 and/or N2; 52.9% IS-Low v 42.2% IS-High; P < .001) and in younger patients (P = .024). Patients with IS-Low tumors had significantly shorter DFS in the CAPOX, FOLFOX, and combined cohorts (mvHR, 1.52 [95% CI, 1.28 to 1.82]; mvHR, 1.58 [95% CI, 1.22 to 2.04]; and mvHR, 1.55 [95% CI, 1.34 to 1.79], respectively; P < .001 all comparisons), regardless of sex, BMI, clinical risk group, tumor location, treatment duration, or chemotherapy regimen. IS prognostic value was greater in younger (≤65 years) than older (>65 years) patients in the CAPOX cohort (mvHR, 1.92 [95% CI, 1.50 to 2.46] v 1.28 [95% CI, 1.01 to 1.63], PINTERACTION = .026), and in DNA mismatch repair proficient than deficient mismatch repair disease (mvHR, 1.68 [95% CI, 1.41 to 2.00] v 0.67 [95% CI, 0.30 to 1.49], PINTERACTION = .03), although these exploratory analyses were uncorrected for multiple testing. Adding IS to a model containing all clinical variables significantly improved prediction of DFS (likelihood ratio test, P < .001) regardless of MMR status. Conclusion IS is prognostic in stage III CRC treated with FOLFOX or CAPOX, including within clinically relevant tumor subgroups. Possible variation in IS prognostic value by age and MMR status, and prediction of benefit from extended adjuvant therapy merit validation

    Evolution des recommandations alimentaires chez les enfants de 3 à 11 ans

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    REIMS-BU Santé (514542104) / SudocSudocFranceF

    La paralysie faciale périphérique (une étude rétrospective des services de neurologie et d'ORL du CHU de Dijon)

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    DIJON-BU Médecine Pharmacie (212312103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

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    The Immunoscore in Localized Urothelial Carcinoma Treated with Neoadjuvant Chemotherapy: Clinical Significance for Pathologic Responses and Overall Survival

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    International audience(1) Background-The five-year overall survival (OS) of muscle-invasive bladder cancer (MIBC) with neoadjuvant chemotherapy and cystectomy is around 50%. There is no validated biomarker to guide the treatment decision. We investigated whether the Immunoscore (IS) could predict the pathologic response to neoadjuvant chemotherapy and survival outcomes. (2) Methods-This retrospective study evaluated the IS in 117 patients treated using neoadjuvant chemotherapy for localized MIBC from six centers (France and Greece). Pre-treatment tumor samples were immunostained for CD3+ and CD8+ T cells and quantified to determine the IS. The results were associated with the response to neoadjuvant chemotherapy, time to recurrence (TTR), and OS. (3) Results-Low (IS-0), intermediate (IS-1-2), and high (IS-3-4) ISs were observed in 36.5, 43.7, and 19.8% of the cohort, respectively. IS was positively associated with a pathologic complete response (pCR; p-value = 0.0096). A high IS was found in 35.7% of patients with a pCR, whereas it was found in 11.3% of patients without a pCR. A low IS was observed in 48.4% of patients with no pCR and in 21.4% of patients with a pCR. Low-, intermediate-, and high-IS patients had five-year recurrence-free rates of 37.2%, 36.5%, and 72.6%, respectively. In the multivariable analysis, a high IS was associated with a prolonged TTR (high vs. low: p = 0.0134) and OS (high vs. low: p = 0.011). (4) Conclusions-This study showed the significant prognostic and predictive roles of IS regarding localized MIBC

    Prognostic and predictive value of Immunoscore and its correlation with ctDNA in stage II colorectal cancer

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    ABSTRACTThis study aimed to validate the prognostic value of Immunoscore (IS) in stage II colorectal cancer (CRC), and explore the roles of IS and circulating tumor DNA (ctDNA) in the adjuvant treatment for early-stage CRC. Resected tumor samples from stage II CRC patients were collected from the Sun Yat-sen University Cancer Center. The densities of CD3+ and CD8+ lymphocytes were quantified and converted to IS and classified into Low, Intermediate (Int), and High groups according to predefined cutoffs. A total of 113 patients were included in the study. Patients with IS-High, Int, and Low were 43 (38%), 62 (55%), and 8 (7%), respectively. Patients with IS-High had an excellent clinical outcome, with none recurring during a median follow-up of 3 years, including 15 (35%) clinical high-risk patients. The 3-year disease-free survival (DFS) was 100% for IS-High, 76% for IS-Int, and 47% for IS-Low (P < .001). In the multivariate Cox analysis, IS was the only significant parameter associated with DFS. IS-Int and IS-Low patients with adjuvant chemotherapy had improved DFS compared to those who did not receive adjuvant chemotherapy (HR = 0.3; 95% CI 0.1–0.92; P = .026). Among the 49 patients with postoperative ctDNA data, IS-High patients had the lowest ctDNA positivity rate, suggesting that they were most eligible for chemotherapy-free treatment. IS had a strong prognostic value in Chinese patients with stage II CRC and demonstrates its clinical utility. IS and ctDNA will jointly optimize the adjuvant treatment strategies for early-stage CRC

    Immunoscore immune checkpoint using spatial quantitative analysis of CD8 and PD-L1 markers is predictive of the efficacy of anti- PD1/PD-L1 immunotherapy in non-small cell lung cancer

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    International audienceBackground Anti-PD-1 and PD-L1 antibodies (mAbs) are approved immunotherapy agents to treat metastatic non-small cell lung cancer (NSCLC) patients. Only a minority of patients responds to these treatments and biomarkers predicting response are currently lacking. Methods Immunoscore-Immune-Checkpoint (Immunoscore-IC), an in vitro diagnostic test, was used on 471 routinesingle FFPE-slides, and the duplex-immunohistochemistry CD8 and PD-L1 staining was quantified using digital-pathology. Analytical validation was performed on two independent cohorts of 206 NSCLC patients. Quantitative parameters related to cell location, number, proximity and clustering were analysed. The Immunoscore-IC was applied on a first cohort of metastatic NSCLC patients (n = 133), treated with anti-PD1 or anti-PD-L1 mAbs. Another independent cohort (n = 132) served as validation. Findings Anti-PDL1 clone (HDX3) has similar characteristics as anti-PD-L1 clones (22C3, SP263). Densities of PD-L1+ cells, CD8+ cells and distances between CD8+ and PD-L1+ cells were quantified and the Immunoscore-IC classification was computed. Using univariate Cox model, 5 histological dichotomised variables (CD8 free of PD-L1+ cells, CD8 clusters, CD8 cells in proximity of PD-L1 cells, CD8 density and PD-L1 cells in proximity of CD8 cells) were significantly associated with Progression-Free Survival (PFS) (all P < 0.0001). Immunoscore-IC classification improved the discriminating power of prognostic model, which included clinical variables andpathologist PD-L1 assessment. In two categories, the Immunoscore-IC risk-score was significantly associated with patients’ PFS (HR = 0.39, 95% CI (0.26–0.59), P < 0.0001) and Overall Survival (OS) (HR = 0.42, 95% CI (0.27–0.65), P < 0.0001) in the training-set. Further increased hazard ratios (HR) were found when stratifying patients into three-category Immunoscore-IC (IS-IC). All patients with Low-IS-IC progressed in less than 18 months, whereas PFS at 36 months were 34% and 33% of High-IS-IC patients in the training and validation sets, respectively.Interpretation Immunoscore-IC is a powerful tool to predict the efficacy of immune-checkpoint inhibitors (ICIs) inpatients with NSCLC
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