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Objective The efficacy of lymph node ratio (LNR) as a prognostic indicator in locally advanced gastric cancer (LAGC) patients underwent radical resection after neoadjuvant immunochemotherapy (NICT) remains to be demonstrated. The objective of the current retrospective study is to investigate the relationship between LNR and survival in patients with LAGC who underwent radical resection after NICT. Methods A retrospective analysis was performed on 121 cases of LAGC in patients underwent radical resection after NICT between July 2020 and October 2023. The LNR values of the patients were divided into two groups using X-tile software. The first group, designated the low LNR group, comprised patients with LNR values of ≤ 33%. The second group, designated the high LNR group, comprised patients with LNR values of > 33%. The correlation between patient survival rates and a range of clinical and pathological variables was examined. Results Overall, 121 patients were enrolled: 108 with low-LNR (LNR ≤ 33%) and 13 with high-LNR (LNR > 33%). A better 2-year overall survival (OS) (88.5% vs. 32.6%; p  < 0.001) and progression-free survival (PFS) (80.2% vs. 23.5%; p  < 0.001) were observed in patients with low LNR. A similar result was also found in those with non-pathological complete response group (non-pCR), where the 2-year OS was 87.2% vs. 32.6% ( p  < 0.001), and the 2-year PFS was 77.7% vs. 23.5% ( p  < 0.001). Compared to the pathologic lymph nodes staging (ypN), LNR exhibited similar prognostic capabilities for OS and PFS. Multivariate analysis indicated that LNR was an independent prognostic factor for both OS ( H R 6.258, 95% CI 1.798–21.778; p  = 0.004) and PFS ( HR 3.431, 95% CI 1.341–8.780; p  = 0.010), but not ypN. Conclusions LNR may serve as a viable indicator for prognostication in LAGC patients treated with NICT.

This study aimed to predict the risks of distant metastasis (DM) of locally advanced rectal cancer (LARC) patients with pathological complete response (pCR) after neoadjuvant chemoradiotherapy (NACRT) and total mesorectal excision (TME), and to find the association between adjuvant chemotherapy (ACT) and their survival outcomes. A total of 242 patients with LARC achieving pCR after NACRT were enrolled in this retrospective study. We developed a nomogram model using logistic regression analyses for predicting risk of DM. The model performance was evaluated by the concordance index and calibration curve. Survival was determined using Kaplan-Meier survival curve. Age, pre-operative CEA, pre-treatment CEA and distance of tumor to anal verge were identified as significantly associated variables that could be enrolled in the model to predict the risk of DM for pCR patients. The nomogram we created had a bootstrapped-concordance index of 0.731 (95% CI = 0.627 to 0.834) and was well calibrated. The high risk group was more likely to develop DM than low risk group (total score) (95% CI = 1.439 to 6.493, = 0.0036). The 1-year, 3-year, and 5-year distant metastasis-free survival (DMFS) for the low and high risk groups (total score ≤ 90 vs > 90) was 97.8%, 94.2%, 94.2% and 91.3%, 83.4%, 81.8%, respectively ( = 0.0036). DM occurred within 1 and 2 years after TME surgery was 33.3% and 55.6% for the low risk group, and 47.3% and 84.2% for the high risk group. The value of ACT was assessed among the whole cohort, patients with cT , with cN or with either DM risk group, but no significant difference was observed concerning DMFS whether ACT was given or not (all > 0.05). Active treatment after DM was more beneficial than palliative treatment ( < 0.001). The nomogram model, including age, pre-operative CEA, pre-treatment CEA and distance to anal verge, predicted the probability of DM among LARC patients achieving pCR after NACRT. The effects of ACT were not seen in different subgroups, while closer clinical follow-up may have greater contribution to pCR patients in the first 2 years, especially for patients with relatively higher risk to develop DM. It is suggested that timely active treatment can bring survival benefit for pCR patients developing DM after NACRT.

BackgroundIn this single-arm study, the efficacy and safety of neoadjuvant pembrolizumab plus chemotherapy were evaluated in patients with resectable esophageal squamous cell carcinoma (ESCC).MethodsThis study included patients with ESCC of clinical stages II–IVA who underwent surgery within 4 to 6 weeks after completing treatment with pembrolizumab (200 mg) combined with a conventional chemotherapy regimen (3 cycles). The safety and efficacy of this combination treatment were evaluated as primary endpoints of the study.ResultsFrom April 2019 to August 2020, a total of 18 patients (including 14 men) were enrolled, of whom 13 patients progressed to surgery. Postoperative pathology revealed a major pathological response (MPR) in 9 cases (9/13, 69.2%) and a pathological complete response (pCR) in 6 cases (6/13, 46.2%). Five patients (5/18, 27.8%) experienced serious treatment-related adverse events (AEs) of grades 3–4. At the time of data cutoff (Mar 25, 2022), the shortest duration of follow-up was 17.8 months. Programmed death-ligand 1 (PD-L1) expression in pretreatment specimens was not significantly associated with the percentage of residual viable tumor (RVT) (r=−0.55, P=0.08). Changes in counts of CD68+ macrophage between pre- and post-treatment specimens were weakly correlated with RVT (r=0.71; P=0.07), while a positive correlation was observed between postoperative forkhead box P3-positive (Foxp3)+T cells/CD4+Tcells ratios and RVT (r=0.84, P = 0.03).ConclusionsThe combination of neoadjuvant immunotherapy and chemotherapy for ESCC is associated with a high pathological response and immunologic effects in the tumor microenvironment (TME). It has acceptable toxicity and great efficacy, suggesting a strong rationale for its further evaluation in randomized clinical trials (RCTs).Trial RegistrationChiCTR2100048917.

Inflammatory blood markers (IBM), such as the neutrophil to lymphocyte ratio (NLR), have emerged as potential prognostic factors in various cancers, including breast cancer (BC), potentially allowing an easy, minimally invasive evaluation of a given cancer‘s prognosis and treatment outcome. We report here a systematic overview of the published data evaluating NLR as a prognostic factor or predictive factor for pathological complete response (PCR) and toxicity in early and advanced BC. A total of 45 articles were identified. NLR was found to be an independent prognostic factor for survival in most of the adjuvant treatment studies. However, no significant correlation was found between survival and NLR for early BC patients receiving neo-adjuvant chemotherapy (NACT) and advanced BC patients. Most studies failed to find a significant correlation between NLR and PCR after NACT. Finally, some data showed that IBM could be predictive of chemotherapy-related toxicity.

Background The purpose of this study was to investigate the value of wavelet-transformed radiomic MRI in predicting the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) for patients with locally advanced breast cancer (LABC). Methods Fifty-five female patients with LABC who underwent contrast-enhanced MRI (CE-MRI) examination prior to NAC were collected for the retrospective study. According to the pathological assessment after NAC, patient responses to NAC were categorized into pCR and non-pCR. Three groups of radiomic textures were calculated in the segmented lesions, including (1) volumetric textures, (2) peripheral textures, and (3) wavelet-transformed textures. Six models for the prediction of pCR were Model I: group (1), Model II: group (1) + (2), Model III: group (3), Model IV: group (1) + (3), Model V: group (2) + (3), and Model VI: group (1) + (2) + (3). The performance of predicting models was compared using the area under the receiver operating characteristic (ROC) curves (AUC). Results The AUCs of the six models for the prediction of pCR were 0.816 ± 0.033 (Model I), 0.823 ± 0.020 (Model II), 0.888 ± 0.025 (Model III), 0.876 ± 0.015 (Model IV), 0.885 ± 0.030 (Model V), and 0.874 ± 0.019 (Model VI). The performance of four models with wavelet-transformed textures (Models III, IV, V, and VI) was significantly better than those without wavelet-transformed textures (Model I and II). In addition, the inclusion of volumetric textures or peripheral textures or both did not result in any improvements in performance. Conclusions Wavelet-transformed textures outperformed volumetric and/or peripheral textures in the radiomic MRI prediction of pCR to NAC for patients with LABC, which can potentially serve as a surrogate biomarker for the prediction of the response of LABC to NAC.

Introduction For patients with locally advanced triple negative breast cancer (TNBC), the standard of care is to administer the KEYNOTE-522 (K522) regimen, including chemotherapy and immunotherapy (pembrolizumab) given in the neoadjuvant setting. Pathological complete response (pCR) is more likely in patients who receive the K522 regimen than in patients who receive standard chemotherapy. Studies have shown that pCR is a strong predictor of long-term disease-free survival. However, factors predicting pCR to K522 are not well understood and require further study in real-world populations. Methods We evaluated 76 patients who were treated with the K522 regimen at our institution. Twenty-nine pre-treatment biopsy slides were available for pathology review. Nuclear grade, Nottingham histologic grade, Ki-67, lymphovascular invasion, and tumor infiltrating lymphocytes (TIL) were evaluated in these 29 cases. For the cases that did not have available slides for review from pre-treatment biopsies, these variables were retrieved from available pathology reports. In addition, clinical staging, race, and BMI at the time of biopsy were retrieved from all 76 patients’ charts. Binary logistic regression models were used to correlate these variables with pCR. Results At the current time, 64 of 76 patients have undergone surgery at our institution following completion of K522 and 31 (48.4%) of these achieved pCR. In univariate analysis, only TIL was significantly associated with pCR ( p  = 0.014) and this finding was also confirmed in multivariate analysis, whereas other variables including age, race, nuclear grade, Nottingham grade, Ki-67, lymphovascular invasion, BMI, pre-treatment tumor size, and lymph node status were not associated with pCR ( p  > 0.1). Conclusion Our real-world data demonstrates high TIL is significantly associated with pCR rate in the K522 regimen and may potentially serve as a biomarker to select optimal treatment. The pCR rate of 48.4% in our study is lower than that reported in K522, potentially due to the smaller size of our study; however, this may also indicate differences between real-world data and clinical trial results. Larger studies are warranted to further investigate the role of immune cells in TNBC response to K522 and other treatment regimens.

Background The focus of this study is to identify particular microRNA (miRNA) signatures in exosomes derived from plasma of 435 human epidermal growth factor receptor 2 (HER2)-positive and triple-negative (TN) subtypes of breast cancer (BC). Methods First, miRNA expression profiles were determined in exosomes derived from the plasma of 15 TNBC patients before neoadjuvant therapy using a quantitative TaqMan real-time PCR-based microRNA array card containing 384 different miRNAs. Forty-five miRNAs associated with different clinical parameters were then selected and mounted on microRNA array cards that served for the quantification of exosomal miRNAs in 435 BC patients before therapy and 20 healthy women. Confocal microscopy, Western blot, and ELISA were used for exosome characterization. Results Quantification of 45 exosomal miRNAs showed that compared with healthy women, 10 miRNAs in the entire cohort of BC patients, 13 in the subgroup of 211 HER2-positive BC, and 17 in the subgroup of 224 TNBC were significantly deregulated. Plasma levels of 18 exosomal miRNAs differed between HER2-positive and TNBC subtypes, and 9 miRNAs of them also differed from healthy women. Exosomal miRNAs were significantly associated with the clinicopathological and risk factors. In uni- and multivariate models, miR-155 ( p  = 0.002, p  = 0.003, respectively) and miR-301 ( p  = 0.002, p  = 0.001, respectively) best predicted pathological complete response (pCR). Conclusion Our findings show a network of deregulated exosomal miRNAs with specific expression patterns in exosomes of HER2-positive and TNBC patients that are also associated with clinicopathological parameters and pCR within each BC subtype.

Purpose The pan-immune-inflammation value (PIV), which reflects the balance between the host immune and inflammatory status, is a readily available index for evaluating cancer outcomes. Until now, however, no study has demonstrated the clinical response of PIV to neoadjuvant immunochemotherapy (NICT) in esophageal squamous cell carcinoma (ESCC). Methods This retrospective study included 218 patients with ESCC who underwent NICT. The relationship between PIV and therapeutic response (pathological complete response [PCR]) and clinical outcomes (overall survival [OS] and disease-free survival [DFS]) was examined. Cox proportional, hazard-regression analyses and the Kaplan–Meier method were used for survival analyses. Recursive partitioning analysis (RPA) was used to establish a novel risk stratification model. Results Sixty-six patients (30.3%) achieved PCR after NICT. Using PCR as the endpoint of interest, patients were compared in groups based on the optimal threshold. PIV was closely related to PCR (odds ratio [OR] 0.311, 95% confidence interval [CI] 0.140–0.690, P  = 0.004). Compared with patients in the low PIV cohort, patients with high PIV had worse 3-year OS (58.7% vs. 83.6%, P  < 0.001) and DFS (51.9% vs. 79.1%, P  < 0.001). PIV was an independent predictor of OS (hazard ratio [HR] 2.364, 95% CI 1.183–4.724, P  = 0.015) and DFS (HR 1.729, 95% CI 1.026–2.913, P  = 0.040). Three risk groups with varied DFS and OS were staged by using an RPA method, and the prognostication accuracy was considerably improved. Conclusions Pretreatment PIV can predict the therapeutic efficacy of NICT for ESCC. Because of better prognostic stratification, pretreatment PIV is a novel, sensitive, and effective indicator in ESCC receiving NICT. The prognostic results of PIV need to be verified in additional prospective studies.

Background The higher pathologic complete response (pCR) after neoadjuvant chemoradiotherapy compared with neoadjuvant chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC) has not translated into significant gains in overall survival. Data on the long-term survival of patients who obtained a pCR after neoadjuvant chemotherapy are scarce. Therefore, this study aimed to evaluate the long-term prognosis and recurrence patterns in these patients. Methods The study enrolled patients with locally advanced ESCC after neoadjuvant chemotherapy followed by surgery in the authors’ hospital between January 2007 and December 2020. The factors predictive of pCR were analyzed. Furthermore, propensity score-matching was performed for those who did and those who did not have a pCR using 1:5 ratio for a long-term survival analysis. Finally, the survival and recurrence patterns of patients obtaining pCR after neoadjuvant chemotherapy were analyzed. Results A pCR was achieved for 61 (8.70%) of the 701 patients in the study. Univariate analysis showed that the patients without alcohol drinking had a higher possibility of obtaining a pCR, although multivariate analysis failed to confirm the difference as significant. After propensity score-matching, the 5-year overall survival was 84.50% for the patients who had a pCR and 52.90% for those who did not ( p < 0.001). Among the 61 patients with a pCR, 9 patients (14.80%) experienced recurrence, including 6 patients with locoregional recurrence and 3 patients with distant metastasis. Conclusion Advanced ESCC patients with pCR after neoadjuvant chemotherapy had a favorable prognosis, yet some still experienced recurrence, particularly locoregional recurrence. Therefore, for this group of patients, regular follow-up evaluation also is needed.

Breast cancer is a heterogeneous disease, and the different biological subtypes have different prognostic impacts. Neoadjuvant trials have recently become popular as they offer several advantages compared to traditional adjuvant trials. Studies have shown that patients who achieve pathological complete response (pCR) after neoadjuvant treatment have a better long-term outcome. Consequently, increasing the rate of pCR became the end point of neoadjuvant trials with the expectation of translation into improved survival. However, the definition of pCR has lacked uniformity, and the prognostic impact of achievement of pCR on survival in different breast cancer subtypes is uncertain. In this review, we present the controversies associated with the use of pCR as an end point in neoadjuvant trials.