Prediction Of Distant Metastasis-free Survival Research Articles

LC3AB protein-based gene (PbG) signatures as an indicator of relapse even after achieving pathological complete response.

e12552 Background: The application of tissue-based quantitative protein and morphological profiling of breast cancer tissues combined with RNA sequencing provides a flexible and generally applicable and scalable method to develop Protein-based Gene (PbG) signatures with significant prognostic value. Methods: A racially and subtype diverse breast cancer cohort (N=555) with available subset of RNA-seq data was used to develop gene expression-based signatures by stratifying patients according to protein expression (IHC) based on survival information and tumor lymphocyte infiltration (TILs) using survival-derived cutoff values. The predictive value of these signatures was then compared with other popular biomarkers scoring systems such as ROR.score, and OncotypeDx (Gene 21). Here we describe the predictive value of these signatures is evaluated by logistic regression modeling of publicly available gene expression data (N=996) from patients receiving neoadjuvant chemotherapy (anthracycline +/- taxane) with a final validation in an independent cohort (N=443) receiving similar therapy. Results: A model of PbG-derived signature from Kaiso, LC3A/B IHC and quantitative TIL-measurements together with ROR score, MAPK, PTEN, Immune and Gene21 signatures show significant prediction of distant metastasis-free survival in all patients: (DMFS, AUC= 0.737, 95% CI: 0.665- 0.819); and in non-pCR patients DMSF (AUC= 0.71, 95% CI: 0.633-0.773). When examining the role of all those markers among the patients who achieved the pCR and had relapse, the LC3A/B PbG-derived score was found to be highly predictive of those patients who would not achieve pCR and ultimately have recurrent disease. Conclusions: PbG-based signatures utilizing on LC3A/B protein values offer a novel and clinically relevant predictive biomarker of response to therapy and relapse in breast cancer patients.

MRI-based Multiregional Radiomics for Pretreatment Prediction of Distant Metastasis After Neoadjuvant Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer

To develop and validate a nomogram based on intratumoral and peritumoral radiomics signatures for pretreatment prediction of distant metastasis-free survival (DMFS) in patients after neoadjuvant chemoradiotherapy (NCRT) with locally advanced rectal cancer (LARC). This retrospective study included 230 patients (161 training cohort; 69 validation cohort) with LARC who underwent NCRT and surgery. Radiomics features were extracted on T2-weighted images from gross tumor volume (GTV) and volumes of 4-mm, 6-mm, and 8-mm peritumoral regions (PTV4, PTV6, and PTV8). The least absolute shrinkage and selection operator (LASSO)-Cox analysis were used for features selection and models construction. The performance of each model in predicting DMFS was evaluated by the Concordance index (C-index) and time-independent receiver operating characteristic curve (ROC). The PTV4 radiomics model demonstrated superior performance compared to the PTV6 and PTV8 radiomics models, with C-indexes of 0.750 and 0.703 in the training and validation cohorts, respectively. The nomogram was constructed by integrating the GTV radiomics signature, PTV4 radiomics signature, and relevant clinical characteristics, including CA19-9 level, clinical T stage, and clinical N stage. The nomogram achieved C-indexes of 0.831 and 0.748, with corresponding AUCs of 0.872 and 0.808 for 5-year DMFS in the training and validation cohorts, respectively. Kaplan-Meier analysis revealed that a cut-off value of 1.653 effectively stratified patients into high- and low-risk groups for DM (P<0.001). The intra-peritumoral radiomics nomogram is a favorable tool for clinicians to develop personalized systemic treatment and intensive follow-up strategies to improve patient prognosis.

Neutrophil to lymphocyte ratio (NLR) for prediction of distant metastasis-free survival (DMFS) in early breast cancer: a propensity score-matched analysis

ObjectiveTo assess the correlation between presurgery neutrophil to lymphocyte ratio (NLR) and distant metastasis-free survival (DMFS) in patients with early breast cancer.DesignRetrospective analysis.Participants300 Caucasian patients with early (T1–2, N0–1, non-metastatic) breast cancer who were followed from July 1999 to June 2015 at our Institution.Main outcome measuresDistant metastasis-free survival (DMFS).ResultsOf whole populations (300 patients), 134 and 166 patients were grouped as low and high NLR, respectively, on the basis of NLR value of 1.97, as established by receiver operating characteristic (ROC) curve analysis (area under curve (AUC)=0.625, p=0.0160). The DMFS rates for 1, 3, 6, 9, 12 and 15 years were better in low NLR patients (100%, 98.9%, 91.7%, 82.7%, 82.7%, 82.7%, respectively), than in high NLR patients (99.4%, 94.3%, 84.5%, 69.2%, 66.0%, 51.4%, respectively), with a statistically significant association. On multivariate analysis, premenopausal status (HR=2.78, 95% CI 1.36 to 5.67, p=0.0049), N1 stage (HR=2.31, 95% CI 1.16 to 4.60, p=0.0167) and a high NLR value (HR=2.64, 95% CI 1.22 to 5.638, p=0.0133) were shown to be independent prognostic factors related to poor recurrence rate. To avoid risk of confounding bias, a propensity score-matched analysis was performed and multivariate analysis according to the Cox model confirmed premenopausal status (HR=2.94, 95% CI 1.25 to 6.93, p=0.0136), N1 stage (HR=2.77, 95% CI 1.25 to 6.12, p=0.0117) and high NLR values (HR=2.52, 95% CI 1.11 to 5.73, p=0.0271), as independent prognostic variables of worse outcome.ConclusionsThis is the first study, to our knowledge, to show a significant correlation between high NLR and worse prognosis in Caucasian patients with early breast cancer by means of propensity score-matched analysis. Further well designed prospective trials with a large sample size are needed to verify our findings and to justify introducing NLR assessment in clinical practice for prediction of cancer recurrence.

Natural history of disease progression in patients who fail to achieve an undetectable prostate-specific antigen level after undergoing radical prostatectomy.

To the authors' knowledge, the natural history of disease progression to distant metastasis is unknown in men who fail to achieve an undetectable prostate-specific antigen (PSA) level after radical retropubic prostatectomy (RRP),. The authors assessed the clinical outcome of men with a persistently detectable PSA level after RRP for clinically localized prostate carcinoma. Between 1989 and 2002, 160 men failed to achieve an undetectable PSA level (>/= 0.1 ng/mL) after undergoing RRP for clinically localized prostate carcinoma. No patient received adjuvant therapy before documented metastasis. The Kaplan-Meier method was used to estimate distant metastasis-free survival. Univariate and multivariate Cox proportional hazards regression was used to assess the ability of clinical and pathologic variables to predict distant metastasis-free survival. The probability of distant metastasis-free survival at 3 years, 5 years, and 10 years was reported to be 68%, 49%, and 22%, respectively. Seventy-five men (47%) developed distant metastases after RRP (median time to metastases of 5.0 years; range, 0.5-13 years). The combination of RRP Gleason score, seminal vesicle status, and lymph node status resulted in 3 risk groups for the prediction of distant metastasis-free survival (hazards ratio [HR] = 1.6; P < 0.01). The slope of PSA changes approximately 3-12 months after RRP at a cutoff value >/= 0.05 was found to be even more predictive of distant metastasis-free survival (HR = 2.9; P < 0.01). Many patients remained free of metastatic disease for an extended period despite failing to achieve an undetectable PSA level after undergoing RRP for clinically localized prostate carcinoma. However, other patients experienced rapid disease progression to distant metastasis. The authors defined clinical (PSA slope) and pathologic (Gleason score) prognostic variables to help identify those patients with a higher risk of developing distant metastasis after undergoing RRP.