Association between homologous recombination deficiency status and carboplatin treatment response in early triple-negative breast cancer.

BACKGROUND: The aim of this study was to assess homologous recombination deficiency (HRD) status and its correlation with carboplatin treatment response in early triple-negative breast cancer (TNBC) patients. METHODS: Tumor tissues from 225 consecutive TNBC patients were evaluated with an HRD panel and homologous recombination-related (HRR) gene expression data. HRD positivity was defined as a high HRD score and/or BRCA1/2 pathogenic or likely pathogenic mutation. Clinicopathological factors, neoadjuvant treatment response, and prognosis were analyzed with respect to HRD status in these TNBC patients. RESULTS: HRD positivity was found in 53.3% of patients and was significantly related to high Ki67 levels (P = 0.001). In patients who received neoadjuvant chemotherapy, HRD positivity (P = 0.005) or a high HRD score (P = 0.003) was significantly associated with a greater pathological complete response (pCR) rate, especially in those treated with carboplatin-containing neoadjuvant regimens (HRD positivity vs. negativity: 50.00% vs. 17.65%, P = 0.040). HRD positivity was associated with favorable distant metastasis-free survival (hazard ratio HR 0.49, 95% confidence interval CI 0.26-0.90, P = 0.022) and overall survival (HR 0.45, 95% CI 0.20-0.99, P = 0.049), irrespective of carboplatin treatment. CONCLUSION: TNBC patients with high HRDs had high Ki67 levels and BRCA mutations. HRD-positive TNBC patients treated with carboplatin had a higher pCR rate. Patients with HRD positivity had a better prognosis, irrespective of carboplatin treatment, warranting further evaluation.

Evaluation of pathological response to neoadjuvant chemotherapy in locally advanced cervical cancer.

Neoadjuvant chemotherapy (NACT) is a viable therapeutic option for women diagnosed locally advanced cervical cancer (LACC). However, the factors influencing pathological response are still controversial. We collected pair specimens of 185 LACC patients before and after receiving NACT and conducted histological evaluation. 8 fresh tissues pre-treatment were selected from the entire cohort to conducted immune gene expression profiling. A novel pathological grading system was established by comprehensively assessing the percentages of viable tumor, inflammatory stroma, fibrotic stroma, and necrosis in the tumor bed. Then, 185 patients were categorized into either the good pathological response (GPR) group or the poor pathological response (PPR) group post-NACT, with 134 patients (72.4%, 134/185) achieving GPR. Increasing tumor-infiltrating lymphocytes (TILs) and tumor-infiltrating lymphocytes volume (TILV) pre-treatment were correlated with GPR, with TILV emerging as an independent predictive factor for GPR. Additionally, CIBERSORT analysis revealed noteworthy differences in the expression of immune makers between cPR and non-cPR group. Furthermore, a significantly heightened density of CD8 + T cells and a reduced density of FOXP3 + T cells were observed in GPR than PPR. Importantly, patients exhibiting GPR or inflammatory type demonstrated improved overall survival and disease-free survival. Notably, stromal type was an independent prognostic factor in multivariate analysis. Our study indicates the elevated TILV in pre-treatment specimens may predict a favorable response to NACT, while identifying stromal type in post-treatment specimens as an independent prognostic factor. Moreover, we proposed this pathological grading system in NACT patients, which may offer a more comprehensive understanding of treatment response and prognosis.

Identification of Optimal Parameters for Assessing Lymph Node Status of Patients with Esophageal Squamous Cell Carcinoma After Neoadjuvant Chemoradiotherapy.

BACKGROUND: This study aimed to compare the prognostic discrimination power of pretreatment pathologic N stage (prepN), lymph node tumor regression grade (LNTRG), and posttreatment pathologic N (ypN) category for esophageal squamous cell carcinoma (ESCC) patients who received neoadjuvant chemoradiotherapy (nCRT) plus surgery. METHODS: The study reviewed 187 ESCC patients from two medical centers who underwent nCRT plus surgery. Pathologic LNTRG was defined by the proportion of viable tumor area within the tumor bed in lymph nodes (LNs). An average LNTRG then was calculated by averaging the tumor regression grade (TRG) score of all resected LNs. Lymph nodes containing regression changes or vital tumor cells were used for interpretation of the prepN stage, which reflects the estimated number of originally involved LNs. RESULTS: The ypN, prepN, and LNTRG categories had significant prognostic stratification power (p < 0.001, log-rank test). Multivariable cox regression showed that all three categories were independent prognostic factors of disease-free survival (DFS) (p < 0.05). The LNTRG category showed a better prognostic value for DFS prediction than the ypN and prepN categories (Akaike information criterion [AIC]: LNTRG [933.69], ypN [937.56], prepN [937.45]). Additionally, the superior predictive capacity of the LNTRG category was demonstrated by decision curve analysis. Similar results were discovered for patients with remaining diseased LNs. CONCLUSIONS: The three staging categories had prognostic relevance for DFS, with the LNTRG category seeming to have better prognostic indication power. Comprehensive consideration of the ypN status, prepN status, and LN regression may allow for better prognostic stratification of patients.

A Comparison of Clinicopathologic Outcomes and Patterns of Lymphatic Spread Across Neoadjuvant Chemotherapy, Neoadjuvant Chemoradiotherapy, and Neoadjuvant Immunochemotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma.

BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) is recommended as the treatment standard for locally advanced esophageal squamous cell carcinoma (ESCC). The use of immunotherapy in the neoadjuvant setting has gained attention. Multiple, clinical trials have explored the efficacy and safety of neoadjuvant immunochemotherapy (NICT). We evaluated the differences in clinicopathologic outcomes and the patterns of lymphatic spread among patients receiving neoadjuvant chemotherapy (NCT), NCRT, and NICT before esophagectomy for locally advanced ESCC. METHODS: A total of 702 patients with ESCC who completed transthoracic esophagectomy followed neoadjuvant therapy were included. Pathological characteristics, including pathologic complete response (pCR), tumor regression grade (TRG) score and patterns of lymphatic spread, were evaluated. RESULTS: Compared with the NCT group, the NCRT group and NICT group had an advantage in pathological response (P < 0.05). The pCR rate was 8.1% in the NCT group, 29.9% in the NCRT group, and 23.6% in the NICT group. The TRG score (P < 0.05) and pathologic T stage (P < 0.05) in the NCT group were significantly higher. Compared with NICT, NCRT can significantly reduce the rate of lymph node metastasis rate in station 1R (0 vs. 3.4%, P < 0.05) and 2R (1.1% vs. 6.8%, P < 0.05). Subgroup analysis according to the tumor location distribution showed that NICT group had higher lymph node metastasis rate in station 2R (9.1%) in middle thoracic cases (P < 0.05) and in station 18 (7.5%) (P < 0.05) in lower thoracic cases. CONCLUSIONS: NCRT or NICT followed by surgery may result in a promising pCR rate and show a better performance in therapeutic response of primary lesion. For patients with lymph node metastasis in station 1R and 2R, NCRT should be the optimal preoperative treatment strategy.

Prognosis of a Heterogeneous TRG Pathological Response to Neoadjuvant Chemotherapy in Patients who Undergo Resection for Colorectal Liver Metastases.

BACKGROUND: Optimal management of colorectal liver metastasis (CRLM) is based on a combination of chemotherapy and surgical resection. The tumor regression grade (TRG) score is a histological scoring system to evaluate response to chemotherapy. The prognosis of a heterogeneous response in cases of multiple metastases has not been evaluated according to the TRG score. PATIENTS AND METHODS: All patients who underwent liver resection for multiple CRLM after neoadjuvant chemotherapy in two tertiary centers from January 2015 to April 2019 were retrospectively included. Oncological characteristics and outcome between TRG 1-2-3 (good response group), TRG 4-5 (poor response group) and heterogeneous TRG (good and poor TRG among different lesions within the same patient) groups were compared. RESULTS: Among the 327 patients included, 134 (41.0%) had good response (TRG 1-2-3), 120 (36.7%) had poor response (TRG 4-5), and 73 (22.3%) had heterogeneous response. The type and number of cycles of chemotherapy, k-Ras mutational status, and tumor number or size did not differ between the three groups. Use of irinotecan-based and anti-VEGF neoadjuvant therapy was associated with better TRG response [irinotecan-based: hazard ratio (OR) = 1.744; p = 0.045; anti-VEGF neoadjuvant therapy: 2.054; p = 0.005). Overall survival (OS) was higher in the 1-2-3 TRG group than in the heterogeneous TRG group (2-year OS = 81.3% vs. 60.3%, respectively; p = 0.003) and the 4-5 TRG group (2-year OS = 81.3% vs. 55.0%, respectively; p = 0.012) and similar between the heterogeneous and 4-5 TRG groups. CONCLUSIONS: The proportion of heterogeneous pathological response according to TRG is 22.3%, and the prognosis is comparable to that of poor pathological response.

Morphological and molecular changes of oestrogen receptor-positive breast cancer following bridging endocrine therapy: a United Kingdom multicentre study.

AIMS: Standard neoadjuvant endocrine therapy (NAET) is used for 6-9 months to downstage hormone-receptor-positive breast cancer. Bridging ET was introduced during the COVID-19 pandemic to delay surgical intervention. There are no data in the literature on the effect of short course therapy on tumour response. We aimed to analyse the effect of bridging ET and validate the previously proposed neoadjuvant ET pathological reporting criteria. METHODS AND RESULTS: This was a multicentre cohort of 256 patients who received bridging ET between March and October 2020. Assessment of paired pre- and post-NAET hormone receptors and HER2 and posttherapy Ki67 expression was done. The median duration of NAET was 45 days. In all, 86% of cases achieved partial pathological response and 9% showed minimal residual disease. Histological response to ET was observed from as early as day 6 posttherapy. Central scarring was noted in 32.8% of cases and lymphocytic infiltrate was seen in 43.4% of cases. Significant changes associated with the duration of ET were observed in tumour grade (21%), with downgrading identified in 12% of tumours (P < 0.001), progesterone receptor (PR) expression with switch to PR-negative status in 26% of cases (P < 0.001), and HER2 status with a switch from HER2-low to HER2-negative status in 32% of cases (P < 0.001). The median patient survival was 475 days, with an overall survival rate of 99.6%. CONCLUSIONS: Changes characteristic of tumour regression and significant changes in PR and HER2 occurred following a short course of NAET. The findings support biomarker testing on pretreatment core biopsies and retesting following therapy.

Gustative Roussy Immune Score is a Predictor for Major Pathological Response in Rectal Cancer: A Result from the Preoperative Intraarterial Chemoembolization Combined with Radiotherapy (PCAR) Study.

Despite the emergence of various treatment strategies for rectal cancer based on neoadjuvant chemoradiotherapy, there is currently a lack of reliable biomarkers to determine which patients will respond well to neoadjuvant chemoradiotherapy. Through collecting hematological and biochemical parameters data of patients prior to receiving neoadjuvant chemoradiotherapy, we evaluated the predictive value of systemic inflammatory indices for pathological response and prognosis in rectal cancer patients. We found that baseline GRIm-Score was an independent predictor for MPR in rectal cancer patients. However, no association was observed between several commonly systemic inflammation indices and long-term outcome.

Exploring treatment outcomes in Stage II-III rectal cancer patients undergoing neoadjuvant therapy at a tertiary care center in Pakistan: a comprehensive analysis of pathological outcomes.

BACKGROUND: Rectal cancer treatment has transformed in recent years, with neoadjuvant treatment (NT) and total neoadjuvant treatment (TNT) aiming to enhance pathological responses. This pioneering study in our country delves into rectal cancer management, offering crucial insights by examining pathological outcomes in patients treated with the NT and TNT approach, shaping the evolving landscape. METHODS: In this retrospective-cohort study spanning January 2017 to December 2022 at a tertiary care hospital in Pakistan, ethical approval was obtained to examine outcomes of two treatments. Patients were divided into TNT (chemoradiation and pre-surgery 5 FU-based chemotherapy) and NT (chemoradiation, surgery, and subsequent 5 FU-based chemotherapy). The primary end-point was response rates-no response, pathological complete response (pCR), near complete response (near CR), and partial response (PR). The Chi-Square Test for Independence assessed the association between treatment response and type (TNT or NT). Data analysis used STATA MP 64; significance was set at p < 0.05 for all two-tailed tests. RESULTS: We analyzed 77 patients, 60 underwent standard neoadjuvant chemoradiation, and 17 followed the total neoadjuvant approach. Predominantly male, most were > 65 with ECOG 0-1. The TNT group showed higher response rates (76% vs 62%, p = 0.039), with 40.38% achieving pCR. In the overall population, pCR and near-CR were similar (27.2% vs 26%), while PR were 14%. Treatment characteristics correlated significantly with chemotherapy type, concurrent chemoradiation, LVI, PNI, and T, N, M staging (p < 0.05). Median overall survival was not reached, and mean survival was 89.1 months (CI: 95.0 to 83.3). Side effects varied, with notable differences in neuropathy, diarrhea, oral mucositis, and thrombocytopenia between NT and TNT groups. CONCLUSION: Our study adds to evidence favoring neoadjuvant approaches in managing rectal cancer in pakistan. Demonstrating a favorable pcr rate, ongoing research with extended follow-up is essential, given the dynamic landscape of rectal cancer treatment for improved patient outcomes.

[18F]FDG PET-CT radiomics signature to predict pathological complete response to neoadjuvant chemoimmunotherapy in non-small cell lung cancer: a multicenter study.

OBJECTIVES: This study aims to develop and validate a radiomics model based on 18F-fluorodeoxyglucose positron emission tomography-computed tomography ([18F]FDG PET-CT) images to predict pathological complete response (pCR) to neoadjuvant chemoimmunotherapy in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: One hundred eighty-five patients receiving neoadjuvant chemoimmunotherapy for NSCLC at 5 centers from January 2019 to December 2022 were included and divided into a training cohort and a validation cohort. Radiomics models were constructed via the least absolute shrinkage and selection operator (LASSO) method. The performances of models were evaluated by the area under the receiver operating characteristic curve (AUC). In addition, genetic analyses were conducted to reveal the underlying biological basis of the radiomics score. RESULTS: After the LASSO process, 9 PET-CT radiomics features were selected for pCR prediction. In the validation cohort, the ability of PET-CT radiomics model to predict pCR was shown to have an AUC of 0.818 (95% confidence interval [CI], 0.711, 0.925), which was better than the PET radiomics model (0.728 [95% CI, 0.610, 0.846]), CT radiomics model (0.732 [95% CI, 0.607, 0.857]), and maximum standard uptake value (0.603 [95% CI, 0.473, 0.733]) (p < 0.05). Moreover, a high radiomics score was related to the upregulation of pathways suppressing tumor proliferation and the infiltration of antitumor immune cell. CONCLUSION: The proposed PET-CT radiomics model was capable of predicting pCR to neoadjuvant chemoimmunotherapy in NSCLC patients. CLINICAL RELEVANCE STATEMENT: This study indicated that the generated 18F-fluorodeoxyglucose positron emission tomography-computed tomography radiomics model could predict pathological complete response to neoadjuvant chemoimmunotherapy, implying the potential of our radiomics model to personalize the neoadjuvant chemoimmunotherapy in lung cancer patients. KEY POINTS: • Recognizing patients potentially benefiting neoadjuvant chemoimmunotherapy is critical for individualized therapy of lung cancer. • [18F]FDG PET-CT radiomics could predict pathological complete response to neoadjuvant immunotherapy in non-small cell lung cancer. • [18F]FDG PET-CT radiomics model could personalize neoadjuvant chemoimmunotherapy in lung cancer patients.

Cytomorphological Disparities in Invasive Breast Cancer Cells following Neoadjuvant Endocrine Therapy and Chemotherapy.

INTRODUCTION: Neoadjuvant endocrine therapy (NAE) offers a breast-conserving surgery rate and clinical response rate similar to those of neoadjuvant chemotherapy (NAC), while presenting fewer adverse events and lower pathological complete response rates. The assessment of pathological response determines degenerative changes and predicts the prognosis of breast cancer treated with NAC. This study clarified the degenerative changes occurring in breast cancer following NAE. METHODS: Our study encompassed two groups: NAE, consisting of 15 patients, and NAC, comprising 18 patients. Tissue samples were obtained from core needle biopsies and surgeries. Nuclear and cell areas were calculated using Autocell analysis. Furthermore, we assessed markers associated with microtubule depolymerization (KIF2A) and initiators of apoptosis (caspase-9). RESULTS: In the NAC group, we observed significant increases in both cytoplasmic and cell areas. These changes in cytoplasm and cells were notably more pronounced in the NAC group compared to the NAE group. After treatment, KIF2A exhibited a decrease, with the magnitude of change being greater in the NET group than in the NAC group. However, no discernible differences were found in caspase-9 expression between the two groups. CONCLUSION: Our findings indicate that NAE induces condensation in cancer cells via cell cycle arrest or apoptosis. Conversely, NAC leads to cell enlargement due to the absence of microtubule depolymerization. These discrepancies underscore the importance of accounting for these distinctions when establishing criteria for evaluating pathological responses.

Does complete pathological response increase perioperative morbidity risk in rectal cancer?

AIM: The optimal management of patients with clinical complete response after neoadjuvant treatment for rectal cancer is controversial. The aim of this study is to compare the morbidity between patients with locally advanced rectal cancer who have had a pathological complete response (pCR) or not after neoadjuvant chemoradiotherapy (NCRT) and total mesorectal excision (TME). The study hypothesis was that pCR may impact the surgical complication rate. METHOD: A retrospective cohort study was conducted of a prospectively maintained database in Australia and New Zealand, the Binational Colorectal Cancer Audit, that identified patients with locally advanced rectal cancer (<15 cm from anal verge) from 1 January 2007 to 31 December 2019. Patients were included if they had locally advanced rectal cancer and had undergone NCRT and proceeded to surgical resection. RESULTS: There were 4584 patients who satisfied the inclusion criteria, 65% being male. The mean age was 63 years and 11% had a pCR (ypT0N0). TME with anastomosis was performed in 67.8% of patients, and the majority of the cohort received long-course radiotherapy (81.7%). Both major and minor complications were higher in the TME without anastomosis group (17.3% vs. 14.7% and 30.6% vs. 20.8%, respectively), and the 30-day mortality was 1.31%. In the TME with anastomosis group, pCR did not contribute to higher rates of surgical complications, but male gender (p < 0.0012), age (p < 0.0001), preoperative N stage (p = 0.0092) and American Society of Anesthesologists (ASA) score ≥3 (p < 0.0002) did. In addition, pCR had no significant effect (p = 0.44) but male gender (p = 0.0047) and interval to surgery (p = 0.015) contributed to higher rates of anastomotic leak. In the TME without anastomosis cohort, the only variable that contributed to higher rates of complications was ASA score ≥3 (p = 0.033). CONCLUSION: Patients undergoing TME dissection for rectal cancer following NCRT showed no difference in complications whether they had achieved pCR or not.

Prognostic significance of a pathological response in metastatic lymph nodes of patients with gastric cancer who underwent neoadjuvant chemotherapy followed by surgery.

PURPOSE: To grade the pathological response of lymph nodes (LNs) to neoadjuvant chemotherapy (NAC) in patients with locally advanced gastric cancer (LAGC) and investigate its prognostic significance. METHODS: This retrospective study included 196 patients who underwent NAC, followed by radical gastrectomy for LAGC between January 2010 and October 2019. Pathological responses were evaluated based on the proportion of residual tumor cells within the tumor area in the primary tumor (PT) and LNs and included the following categories: 1a (0%), 1b (< 10%), 2 (10-50%), and 3 (> 50%). RESULTS: Among 166 patients with clinically node-positive disease, 38/27/39/62 were classified as having LN regression grade (LRG) 1a/1b/2/3, respectively. Compared to LN non-responders (LRG 2 or 3), LN responders (LRG 1a or 1b) had significantly higher 5-year overall survival (72.5% vs. 19.0%, P < 0.001) and recurrence-free survival rates (67.8% vs. 22.2%, P < 0.001), irrespective of PT response. Furthermore, a multivariate analysis revealed that the LN response was an independent risk factor for the overall survival (hazard ratio [HR] 0.417, 95% confidence interval [CI] 0.181-0.962, P = 0.040) and recurrence-free survival (HR 0.490, 95% CI 0.242-0.991, P = 0.047), but not the PT response (P > 0.05). CONCLUSIONS: The pathological LN response may be a reliable prognostic prediction tool in patients with LAGC who received NAC.

Comparison of different criteria for estimating major pathological response in resectable non-small cell lung cancer treated with neoadjuvant chemoimmunotherapy.

BACKGROUND: Major pathological response (MPR) is proposed as a surrogate endpoint for survival in non-small cell lung cancer (NSCLC) after neoadjuvant chemoimmunotherapy. However, the criteria for estimating MPR differ between the recommendations of the International Association for the Study of Lung Cancer (IASLC) and the immune-related pathologic response criterion (irPRC). IASLC's criteria focus solely on evaluating the primary tumor, while irPRC's criteria encompass both the primary tumor and lymph node metastasis. Our objective is to compare the prognostic value of different criteria for estimating MPR. METHODS: We conducted a retrospective study on a cohort of 235 patients with NSCLC after neoadjuvant chemoimmunotherapy. The survival endpoint was event-free survival (EFS). The MPR status of each patient was evaluated using both IASLC's criteria and irPRC's criteria. The prognostic value was compared using the Area Under Curve (AUC). RESULTS: The MPR rates were 63.4 % (149/235) and 57.4 % (135/235) according to IASLC's and irPRC's criteria, respectively. Inconsistent cases, characterized by MPR status according to IASLC's criteria but non-MPR status according to irPRC's criteria, constituted 6.0 % (14/235) of the overall cohort and 15.2 % (14/92) of patients with pretreatment N positive disease. Interestingly, all inconsistent patients showed no recurrence during the study period. Although both MPR statuses according to IASLC (p = 0.00039) and irPRC (p = 0.0094) were associated with improved EFS, IASLC's criteria (AUC = 0.65) were superior to irPRC's criteria (AUC = 0.62) with a higher AUC value. CONCLUSION: IASLC's criteria for estimating MPR were superior to irPRC's criteria in predicting EFS for NSCLC after neoadjuvant chemoimmunotherapy.

Prolonged interval to surgery following neoadjuvant chemoradiotherapy in locally advanced rectal cancer: A meta-analysis of randomized controlled trials.

BACKGROUND: Long-course neoadjuvant chemoradiotherapy (NCRT), followed by surgery after an interval of 6-8 weeks, represents standard of care for patients with locally advanced rectal cancer (LARC). Increasing this interval may improve rates of complete pathological response (pCR) and tumour downstaging. We performed a meta-analysis comparing standard (SI, within 8 weeks) versus longer (LI, after 8 weeks) interval from NCRT to surgery. METHODS: PubMed, Embase, and Cochrane databases were searched up to 31 August 2022. Randomized controlled trials (RCTs) comparing SI with LI after NCRT for LARC were included. The primary endpoint was pCR rate. Secondary endpoints included rates of R0 resection, circumferential resection margin positivity (+CRM), TME completeness, lymph node yield (LNY), operative duration, tumour downstaging (TD), sphincter preservation, mortality, postoperative complications, surgical site infection (SSI) and anastomotic leak (AL). Random effects models were used to calculate pooled effect size estimates. RESULTS: Four RCTs encompassing 867 patients were included. There were 539 males (62.1%). LI was associated with a higher pCR rate (OR 0.61, 95%CI â€‹= â€‹0.39-0.95, p â€‹= â€‹0.03), and more TD (OR 0.60, 95%CI â€‹= â€‹0.37-0.97, p â€‹= â€‹0.04) compared to SI. However, there was no difference in rates of R0 resection (p â€‹= â€‹0.87), +CRM (p â€‹= â€‹0.66), sphincter preservation (p â€‹= â€‹0.26), incomplete TME (p â€‹= â€‹0.49), LNY (p â€‹= â€‹0.55), SSI (p â€‹= â€‹0.33), AL (p â€‹= â€‹0.20), operative duration (p â€‹= â€‹0.07), mortality (p â€‹= â€‹0.89) or any surgical complication (p â€‹= â€‹0.91). CONCLUSIONS: A LI to surgery after NCRT for LARC increases pCR and TD rates. Local recurrence or survival were not assessed due to unavailable data. We recommend deferring TME until after an interval of 8 weeks following completion of NCRT.

Pathological Changes Following Neoadjuvant Endocrine Therapy (NAET): A Multicentre Study of 391 Breast Cancers.

Oestrogen receptor (ER)-positive breast cancer (BC) is generally well responsive to endocrine therapy. Neoadjuvant endocrine therapy (NAET) is increasingly being used for downstaging ER-positive tumours. This study aims to analyse the effect of NAET on a well-characterised cohort of ER-positive BC with particular emphasis on receptor expression. This is a retrospective United Kingdom (UK) multicentre study of 391 patients who received NAET between October 2012 and October 2020. Detailed analyses of the paired pre- and post-NAET morphological changes and hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) expression were performed. The median duration of NAET was 86 days, with median survival and overall survival rates of 380 days and 93.4%, respectively. A total of 90.3% of cases achieved a pathological partial response, with a significantly higher rate of response in the HER2-low cancers. Following NAET, BC displayed some pathological changes involving the tumour stroma including central scarring and an increase in tumour infiltrating lymphocytes (TILs) and tumour cell morphology. Significant changes associated with the duration of NAET were observed in tumour grade (30.6% of cases), with downgrading identified in 19.3% of tumours (p < 0.001). The conversion of ER status from positive to low or negative was insignificant. The conversion of progesterone receptor (PR) and HER2 status to negative status was observed in 31.3% and 38.1% of cases, respectively (p < 0.001). HER2-low breast cancer decreased from 63% to 37% following NAET in the paired samples. Significant morphological and biomarker changes involving PR and HER2 expression occurred following NAET. The findings support biomarker testing on pre-treatment core biopsies and post-treatment residual carcinoma.

Transforming breast cancer care: harnessing the power of artificial intelligence and imaging for predicting pathological complete response. a narrative review.

This narrative review explores the transformative potential of Artificial Intelligence (AI) and advanced imaging techniques in predicting Pathological Complete Response (pCR) in Breast Cancer (BC) patients undergoing Neo-Adjuvant Chemotherapy (NACT). Summarizing recent research findings underscores the significant strides made in the accurate assessment of pCR using AI, including deep learning and radiomics. Such AI-driven models offer promise in optimizing clinical decisions, personalizing treatment strategies, and potentially reducing the burden of unnecessary treatments, thereby improving patient outcomes. Furthermore, the review acknowledges the potential of AI to address healthcare disparities in Low- and Middle-Income Countries (LMICs), where accessible and scalable AI solutions may enhance BC management. Collaboration and international efforts are essential to fully unlock the potential of AI in BC care, offering hope for a more equitable and effective approach to treatment worldwide.

The role of FDG PET/CT radiomics in the prediction of pathological response to neoadjuvant treatment in patients with esophageal cancer.

Background: Attainment of a complete histopathological response following neoadjuvant therapy has been associated with favorable long-term survival outcomes in esophageal cancer patients. We investigated the ability of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) radiomic features to predict the pathological response to neoadjuvant treatment in patients with esophageal cancer. Materials and methods: A retrospective review of medical records of patients with locally advanced resectable esophageal or esophagogastric junctional cancers. Included patients had a baseline FDG PET/CT scan and underwent Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) protocol followed by surgery. Four demographic variables and 107 PET radiomic features were extracted and analyzed using univariate and multivariate analyses to predict response to neoadjuvant therapy. Results: Overall, 53 FDG-avid primary esophageal cancer lesions were segmented and radiomic features were extracted. Seventeen radiomic features and 2 non-radiomics variables were found to exhibit significant differences between neoadjuvant therapy responders and non-responders. An unsupervised hierarchical clustering analysis using these 19 variables classified patients in a manner significantly associated with response to neoadjuvant treatment (p < 0.01). Conclusion: Our findings highlight the potential of FDG PET/CT radiomic features as a predictor for the response to neoadjuvant therapy in esophageal cancer patients. The combination of these radiomic features with select non-radiomic variables provides a model for stratifying patients based on their likelihood to respond to neoadjuvant treatment.

Peripheral blood inflammatory biomarkers dynamics reflect treatment response and predict prognosis in non-small cell lung cancer patients with neoadjuvant immunotherapy.

Neoadjuvant immunotherapy has significantly changed the therapeutic approach for treating patients with surgically resectable non-small cell lung cancer (NSCLC). Here, peripheral blood inflammation-based biomarkers as well as previously less focused eosinophil fraction, modified Glasgow prognostic score (mGPS), and prognostic nutritional index (PNI) were systematically included to comprehensively analyze their potential in predicting neoadjuvant immunotherapy efficacy and prognosis. We enrolled 189 patients (94 in training and 95 in validation cohorts) with stage I-III B surgically resectable NSCLC treated with neoadjuvant immunotherapy from the National Cancer Center of China. Baseline and post-treatment eosinophils fraction, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), monocyte-to-lymphocyte ratio (MLR), PNI, mGPS, and their changes were calculated and analyzed for correlation with neoadjuvant immunotherapy efficacy and prognosis. In patients in the major pathological response (MPR) group, the post-treatment eosinophil fraction was significantly high, and NLR, PLR, SII, and MLR were significantly lower compared to the non-MPR group in both the training and validation cohorts. The receiver operating characteristic curve showed that post-treatment, eosinophil fraction and SII and their changing were two of the most important factors. Univariate and multivariate logistic regression analyses showed that post-treatment eosinophil fraction, SII, mGPS, and ΔSII could independently predict MPR in patients treated with neoadjuvant immunotherapy. Survival analysis showed a significant correlation between high post-treatment NLR, PLR, SII, mGPS, and their changes in ΔNLR and ΔSII elevation with poor overall survival and event-free survival of patients. Our results suggest that inflammatory biomarkers could predict the patient's response to neoadjuvant immunotherapy and prognosis.

Tumor immune microenvironment predicts the pathologic response of neoadjuvant chemoimmunotherapy in non-small-cell lung cancer.

The clinical outcome of resectable non-small-cell lung cancer (NSCLC) patients receiving neoadjuvant chemoimmunotherapy is good but varies greatly. In addition, the pathological response after neoadjuvant chemoimmunotherapy is significantly associated with survival outcomes. The aim of this retrospective study was to identify which population of patients with locally advanced and oligometastatic NSCLC has a favorable pathological response after neoadjuvant chemoimmunotherapy. NSCLC patients treated with neoadjuvant chemoimmunotherapy were enrolled between February 2018 and April 2022. Data on clinicopathological features were collected and evaluated. Multiplex immunofluorescence was performed on pre-treatment puncture specimens and surgically resected specimens. In total, 29 patients with stages III and IV locally advanced or oligometastatic NSCLC who received neoadjuvant chemoimmunotherapy and R0 resection were enrolled. The results showed that 55% (16/29) of patients had a major pathological response (MPR) and 41% (12/29) of patients had a complete pathological response (pCR). In the stroma area of the pre-treatment specimen, the higher infiltration of CD3+ PD-L1+ tumor-infiltrating lymphocytes (TILs) and the lower infiltration of CD4+ and CD4+ FOXP3+ TILs were more likely to appear in patients with pCR. However, in the tumor area, the higher infiltration of CD8+ TILs was more likely to appear in patients with non-MPR. In the post-treatment specimen, we found increased infiltration of CD3+ CD8+ , CD8+ GZMB+ , and CD8+ CD69+ TILs and decreased infiltration of PD-1+ TILs both in the stroma and tumor areas. Neoadjuvant chemoimmunotherapy achieved an MPR rate of 55% and induced greater immune infiltration. In addition, we observed that the baseline TILs and their spatial distribution correlate to the pathological response.

The predictive value of inflammatory biomarkers for major pathological response in non-small cell lung cancer patients receiving neoadjuvant chemoimmunotherapy and its association with the immune-related tumor microenvironment: a multi-center study.

BACKGROUND: Inflammatory biomarkers in the peripheral blood have been established as predictors for immunotherapeutic efficacy in advanced non-small cell lung cancer (NSCLC). Whether they can also predict major pathological response (MPR) in neoadjuvant setting remains unclear. METHODS: In this multi-center retrospective study, 122 and 92 stage I-IIIB NSCLC patients from six hospitals who received neoadjuvant chemoimmunotherapy followed by surgery were included in the discovery and external validation cohort, respectively. Baseline and on-treatment neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and systemic immune-inflammation index (SII) were calculated and associated with MPR. Furthermore, resected tumor samples from 37 patients were collected for RNA-sequencing to investigate the immune-related tumor microenvironment. RESULTS: In both the discovery and validation cohorts, the on-treatment NLR, dNLR, PLR, and SII levels were significantly lower in the patients with MPR versus non-MPR. On-treatment SII remained an independent predictor of MPR in multivariate logistic regression analysis. The area under the curve (AUC) of on-treatment SII for predicting MPR was 0.75 (95%CI, 0.67-0.84) in the discovery cohort. Moreover, the predictive value was further improved by combining the on-treatment SII and radiological tumor regression data, demonstrating an AUC of 0.82 (95%CI, 0.74-0.90). The predictive accuracy was validated in the external cohort. Compared with the SII-high group, patients with SII-Low were associated with the activated B cell receptor signaling pathway and a higher intratumoral immune cell infiltration level. CONCLUSIONS: On-treatment SII was independently associated with MPR in NSCLC patients receiving neoadjuvant chemoimmunotherapy. Further prospective studies are warranted.