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OBJECTIVE: Triple-negative breast cancer (TNBC) presents a clinical challenge as an aggressive tumor, correlated with unfavorable prognosis. Tumor-infiltrating lymphocytes (TILs) have garnered interest as a potential prognostic biomarker. However, the disparity in outcomes between varying TILs rates remains inadequately explored. METHODS: PubMed, Scopus, Web of Science, and Cochrane databases were searched for studies about the prognostic value of TILs in patients with TNBC receiving neoadjuvant chemotherapy. The hazard ratios (HRs) or odds ratios (ORs) were computed for binary endpoints, with 95% confidence intervals (CIs). RESULTS: Twenty-nine studies were included, involving a population of six thousand one hundred sixty-one (80.41%) with TNBC. The cut-off TILs value ranged from 10 to 60%, with 50% being the most related value. Compared with the low-TIL expression group, the disease-free survival (DFS) (HR 0.71; 95% CI 0.61-0.82; p < 0.00001) and overall survival (OS) (HR 0.76; 95% CI 0.63-0.90; p = 0.002) rates showed significant improvement with higher TIL infiltrations. In the subgroup analyses of the lymphocyte subtypes CD4 + and CD8 + , there was statistical significance favoring higher TILs rates in both subtypes, each associated with improved DFS (HR 0.48; 95% CI 0.33-0.71; p = 0.0002) and OS (HR 0.53; 95% CI 0.36-0.78; p = 0.001), regardless of which cell subtype was predominantly infiltrated. The complete pathological response analysis showed better rates for the higher TIL group than the control for both the TIL (OR 1.29; 95% CI 1.13-1.48; p = 0.0003) and Ki-67 (OR 2.74; 95% CI 2.01-3.73; p < 0.00001) analyses. CONCLUSION: Higher expressions of TILs in patients with TNBC were associated with improved significantly DFS, OS, and pCR outcomes.

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BACKGROUND: Locally advanced rectal cancer (LARC) typically involves neoadjuvant chemoradiotherapy (nCRT) followed by surgery (total mesorectal excision, TME). While achieving a complete pathological response (pCR) is a strong indicator of a positive prognosis, the specific benefits of adjuvant chemotherapy after pCR remain unclear. To address this knowledge gap, we conducted a systematic review and meta-analysis to assess the potential advantages of adjuvant therapy in patients who achieve pCR. METHODS: In this study, we searched Medline, Embase, and Web of Science databases for relevant research. We focused on binary outcomes, analyzing them using odds ratios (ORs) with 95% confidence intervals (CIs). To account for potential variability between studies, all endpoints were analyzed with DerSimonian and Laird random-effects models. We assessed heterogeneity using the I2 statistic and employed the R statistical software (version 4.2.3) for all analyses. RESULTS: Thirty-four studies, comprising 31,558 patients, were included. The outcomes demonstrated a significant difference favoring the AC group in terms of overall survival (OS) (HR 0.75; 95% CI 0.60-0.94; p = 0.015; I2 = 0%), and OS in 5 years (OR 1.65; 95% CI 1.21-2.24; p = 0.001; I2 = 39%). There was no significant difference between the groups for disease-free survival (DFS) (HR 0.94; 95% CI 0.76-1.17; p = 0.61; I2 = 17%), DFS in 5 years (OR 1.19; 95% CI 0.82-1.74; p = 0.36; I2 = 43%), recurrence-free survival (RFS) (HR 1.10; 95% CI 0.87-1.40; p = 0.39; I2 = 0%), and relapse-free survival (OR 1.08; 95% CI 0.78-1.51; p = 0.62; I2 = 0%). CONCLUSION: This systematic review and meta-analysis found a significant difference in favor of the ACT group in terms of survival after pCR. Therefore, the administration of this treatment as adjuvant therapy should be encouraged in clinical practice.

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PURPOSE: Systemic immune-inflammatory markers have a certain predictive role in pathological complete response (pCR) after neoadjuvant treatment (NAT) in breast cancer. However, there is a lack of research exploring the predictive value of markers after treatment. METHODS: This retrospective study collected data from 1994 breast cancer patients who underwent NAT. Relevant clinical and pathological characteristics were included, and pre- and post-treatment complete blood cell counts were evaluated to calculate four systemic immune-inflammatory markers: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII). The optimal cutoff values for these markers were determined using ROC curves, and patients were classified into high-value and low-value groups based on these cutoff values. Univariate and multivariate logistic regression analyses were conducted to analyze factors influencing pCR. The factors with independent predictive value were used to construct a nomogram. RESULTS: After NAT, 383 (19.2%) patients achieved pCR. The area under the ROC curve is generally larger for post-treatment markers compared to pre-treatment markers. Pre-treatment NLR and PLR, as well as post-treatment LMR and SII, were identified as independent predictive factors for pCR, along with Ki-67, clinical tumor stage, clinical lymph node stage, molecular subtype, and clinical response. Higher pre-NLR (OR = 1.320; 95% CI 1.016-1.716; P = 0.038), pre-PLR (OR = 1.474; 95% CI 1.058-2.052; P = 0.022), post-LMR (OR = 1.532; 95% CI 1.175-1.996; P = 0.002), and lower post-SII (OR = 0.596; 95% CI 0.429-0.827; P = 0.002) are associated with a higher likelihood of achieving pCR. The established nomogram had a good predictive performance with an area under the ROC curve of 0.754 (95% CI 0.674-0.835). CONCLUSION: Both pre- and post-treatment systemic immune-inflammatory markers have a significant predictive role in achieving pCR after NAT in breast cancer patients. Indeed, it is possible that post-treatment markers have stronger predictive ability compared to pre-treatment markers.

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Watch-and-wait has emerged as a new strategy for the management of rectal cancer when a complete clinical response is achieved after neoadjuvant therapy. In an attempt to standardize this new clinical approach, initiated by the Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD), and with the participation of the Spanish Association of Coloproctology (AECP), the Spanish Society of Pathology (SEAP), the Spanish Society of Gastrointestinal Endoscopy (SEED), the Spanish Society of Radiation Oncology (SEOR), and the Spanish Society of Medical Radiology (SERAM), we present herein a consensus on a watch-and-wait approach for the management of rectal cancer. We have focused on patient selection, the treatment schemes evaluated, the optimal timing for evaluating the clinical complete response, the oncologic outcomes after the implementation of this strategy, and a protocol for surveillance of these patients.

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OBJECTIVE: To investigate the effects of HER2-low expression (HER2-low) and HER2-zero expression (HER2-0) on the pathological complete response (pCR) rate and survival of patients following neoadjuvant chemotherapy. METHODS: Eighty-six patients were followed up. Patients were divided into HER2-0 (immunohistochemistry (IHC) score of 0 (IHC0)) and HER2-low (IHC1+ or IHC2+/in situ hybridization non-amplified (ISH-)) groups according to the IHC detection of puncture tissues. After neoadjuvant chemotherapy, the clinical characteristics, pCR rate and DFS were compared between the two groups. RESULTS: There were 24 (27.9%) cases with HER2-0 and 62 (72.1%) cases with HER2-low. Hormone receptor-positive (HR+) patients accounted for 77.4% of the HER2-low group, which was higher than 70.8% in the HER2-0 group, and there was no significant difference between the two groups (p = 0.524). There were statistical differences in the pT and pN stages between HER2-low and HER2-0 subgroups in the triple-negative breast cancer (TNBC) group after neoadjuvant chemotherapy. The HER2-low subgroup had an earlier T stage (p = 0.009), and the ratio of N0 to N1 in the HER2-low and HER2-0 subgroups was 92.9% and 71.4%, respectively (p = 0.037). The Ki-67 index and median PR value were significantly lower in the HER2-low group after neoadjuvant chemotherapy (p = 0.002, p = 0.018). The HER2 IHC score was altered in the HER2-low group, and the HER-2 (2+) score changed significantly (p = 0.002). Seventy-eight patients with complete immunohistochemical data were analyzed. The discordance rate of the IHC score of HER2 after neoadjuvant chemotherapy was 38.5%, and eight patients with HER2-low showed HER2-0 status, with a discordance rate of 10.3%. After neoadjuvant chemotherapy, The pCR rate was significantly lower in the HER2-low group compared with that in the HER2-0 group (4.8% vs. 8.3%; p = 0.914), but the recurrence and metastasis rates were lower in the HER2-low group (9.7% vs. 20.8%; p = 0.165). There were no differences in DFS between the two groups at 6, 12, 24, and 36 months (p = 0.076; p = 0.518; p = 0.245; p = 0.406). The subgroup analysis demonstrated no significant difference in DFS between HER2-low and HER2-0 subgroups in the HR + and TNBC groups (p = 0.141, p = 0.637). CONCLUSION: This retrospective study indicates that HER2-low has no significant effect on neoadjuvant efficacy in operable breast cancer. There were no statistical differences in clinical characteristics, pCR rate, and DFS between the HER2-low and the HER2-0 groups. There was no evidence that a HER2-low status constitutes a unique biological subtype, suggesting that more clinical data might be needed to verify these observations.

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SUMMARY OBJECTIVE: Patients with residual disease after neoadjuvant chemotherapy have a relative risk of developing recurrence. This study investigates the risk factors for recurrence in locally advanced breast cancer patients with residual disease and evaluates survival analysis. METHODS: This is a retrospective, single-center study. Breast cancer patients who failed to achieve a pathological complete response after neoadjuvant chemotherapy were included. Demographic, clinicopathological, and treatment characteristics were evaluated to identify predictive factors of recurrence and survival analysis. RESULTS: We included 205 patients in this study. After a median of 31 months of follow-up, 10 patients died, and 20 developed distant metastasis. Disease-free survival and disease-specific survival were 73.8% and 83.1%, respectively. Lymphovascular invasion and non-luminal subtype were independent predictors of locoregional recurrence. In situ carcinoma, lymphovascular invasion, ypTIII stage, and non-luminal molecular subtypes were independent predictors of disease-free survival. The only independent factor affecting disease-specific survival was cNII-III. The number of involved lymph nodes was an independent predictor of disease-free survival in patients without complete axillary response. CONCLUSION: Factors affecting disease-specific survival and disease-free survival were cNII-III and the number of involved lymph nodes, respectively. Patients with non-luminal, large residual tumors with in situ carcinoma, lymphovascular invasion, clinically positive axilla, and residual nodal involvement have a high relative risk for recurrence and may benefit from additional treatments.

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Liquid biopsy is increasingly vital in monitoring neoadjuvant breast cancer treatment. This study collected plasma samples at three time points from participants in the Neoadjuvant Carboplatin in Triple Negative Breast Cancer (NACATRINE), analyzing miRNA expression with NanoString's nCounter® Human v3 miRNA assay. In the carboplatin arm, four ct-miRNAs exhibited dynamic changes linked to pathologic complete response, with a combined area under the curve of 0.811. Similarly, the non-carboplatin arm featured four ct-miRNAs with an area under the curve of 0.843. These findings underscore the potential of ct-miRNAs as personalized tools in breast cancer treatment, assisting in predicting treatment response and assessing the risk of relapse. Integrating ct-miRNA analysis into clinical practice can optimize decisions and enhance patient outcomes.

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OBJECTIVES: We aimed to evaluate the pCR rate in patients receiving NAC for the treatment of breast cancer (BC) in a multicenter cohort in Brazil. Additionally, we aimed to use RWD to assess the impact of pCR on OS and DFS. METHODS: This was a retrospective, multicenter cohort study that included female patients over 18 years of age who were diagnosed with nonmetastatic breast cancer and received NAC. OS and DFS at five years were estimated by the Kaplan‒Meier method. Additionally, we conducted a multivariate analysis to identify factors that were significantly associated with pCR and OS. RESULTS: From 2011 to 2020, 1891 patients were included in the study, and 421 (22,3%) achieved pCR (ypT0 ypN0). Considering the presence of residual DCIS, pCR was achieved in 467 patients (23,5%). The pCR rate varied between the subtypes: HER-2+ (p = 0,016) and clinical stage IIIA and IIIB (p < 0,001). Among HER-2+ patients, those who received trastuzumab had a significantly higher pCR rate than those who did not receive trastuzumab (p < 0.0001). Similarly, patients with TNBC who received treatment with platinum-based regimens also showed higher pCR rates (p < 0.0001). OS was grouped according to pCR status, and the OS rate was 88,3% in the pCR group and 58.1% in the non-pCR group (p < 0.0001). The five-year DFS was 92.2% in the pCR group and 64.3% in the non-pCR group (p < 0.0001). CONCLUSION: The pCR rate and its prognostic value varied across BC subtypes. In our study, pCR could be used as a surrogate of favorable clinical outcome, as it was associated with higher OS and DFS rates.

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Background: Short-course radiotherapy (SCRT) of 25 Gy in five daily fractions is a recommended strategy in the neoadjuvant setting for resectable locally advanced rectal cancer (LARC), as well as in cases of metastatic disease for local control. There is scarce information regarding the use of SCRT for patients who have received nonoperative management. Objectives: To describe the characteristics of patients who received treatment with SCRT for LARC and metastatic rectal cancer, toxicity, and the approach after radiation treatment. Methods: This is a retrospective analysis of all patients who underwent SCRT for rectal cancer at the Alexander Fleming Institute from March 2014 to June 2022. Results: In total, 44 patients were treated with SCRT. The majority were male (29, 66%), with a median age of 59 years (interquartile range 46-73). Most patients had stage IV disease (26, 59.1%), followed by LARC (18, 40.9%). Most lesions were located in the middle rectum (30, 68%). The majority of LARC patients underwent SCRT followed by consolidation chemotherapy (ChT) (16/18, 89%), while most patients with metastatic disease underwent SCRT followed by consolidation ChT (14/26, 53.8%). A clinical complete response (cCR) was documented in 8/44, 18.2% of patients. Most patients with LARC and cCR were managed by a watch and wait approach (5/18, 27.7%). Local recurrence was observed in LARC cases (2/18, 11.1%). Patients who underwent SCRT following consolidation ChT were more likely to have adverse events (AEs) than those undergoing induction ChT following SCRT (11/30, 36.7% versus 3/12, 25%, p = 0.02). Conclusion: In a subgroup of patients diagnosed with LARC and treated with SCRT followed by ChT, surgical treatment could be omitted after they achieved a cCR. Local recurrence was similar to that reported in a previous study. SCRT is a reasonable option for local disease control in stage IV disease, yielding low toxicity rates. Therefore, decisions must be made by a multidisciplinary team. Prospective studies are necessary to reach further conclusions.

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BACKGROUND: Watch-and-wait strategy has been increasingly accepted for patients with clinical complete response (cCR) after multimodal treatment for locally advanced rectal adenocarcinoma. Close follow-up is essential to the early detection of local regrowth. It was previously demonstrated that probe-based confocal laser endomicroscopy (pCLE) scoring using the combination of epithelial and vascular features might improve the diagnostic accuracy of cCR. AIM: To validate the pCLE scoring system in the assessment of patients with cCR after neoadjuvant chemoradiotherapy (nCRxt) for advanced rectal adenocarcinoma. METHODS: Digital rectal examination, pelvic magnetic resonance imaging (MRI), and pCLE were performed in 43 patients with cCR, who presented either a scar (N = 33; 76.7%) or a small ulcer with no signs of tumor, and/or biopsy negative for malignancy (N = 10; 23.3%). RESULTS: Twenty-five (58.1%) patients were men, and the mean age was 58.4 years. During the follow-up, 12/43 (27.9%) patients presented local regrowth and underwent salvage surgery. There was an association between pCLE diagnostic scoring and final histological report (for patients who underwent surgical resection) or final diagnosis at the latest follow-up (p = 0.0001), while this association was not observed with MRI (p = 0.49). pCLE sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 66.7%, 93.5%, 80%, 88.9%, and 86%, respectively. MRI sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 66.7%, 48.4%, 66.7%, 78.9%, and 53.5%, respectively. CONCLUSIONS: pCLE scoring system based on epithelial and vascular features improved the diagnosis of sustained cCR and might be recommended during follow-up. pCLE might add some valuable contribution for identifying local regrowth. Trial Registration This protocol was registered at the Clinical Trials (ClinicalTrials.gov identifier NCT02284802).

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