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Purpose: To investigate the predictive value of 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) PET/CT for evaluating primary tumor (PT) and lymph node (LN) responses after neoadjuvant programmed death-ligand 1 (PD-L1) blockade monotherapy in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). Methods: In the single-arm phase 1b NATION-1907 trial (NCT04215471), 23 patients with LA-ESCC received two cycles of neoadjuvant PD-L1 blockade Adebrelimab followed by surgery. Among these, 18 patients underwent [18F]FDG PET/CT scans both before immunotherapy and prior to surgery. Standardized uptake value corrected for lean body mass (SUL)-derived parameters, including SULmax and SULpeak, were documented for PTs and LNs. Lesions > 1cm3 were segmented using thresholds of 41% and 50% of SULmax, respectively, following European Association of Nuclear Medicine (EANM) guidelines, with metabolic tumor volume (MTV) and total lesion glycolysis (TLG) calculated. Percentage changes of all metabolic parameters were also recorded. Residual viable tumor ≤ 33% were classified as well-responders, whereas residual viable tumor > 33% were classified as poor-responders based on histological evaluation. Results: In the PT analysis, 10 patients were classified as PT well-responders and 8 as PT poor-responders. All post-treatment metabolic parameters, except MTV, were significantly lower in well-responders compared to poor-responders. The %ΔMTV, %ΔTLG were significantly higher in the poor-responder group (all P < 0.05). ROC curves indicated %ΔMTV41 exhibited optimum performance in predicting well-responders, with an AUC of 0.875 (cut-off: -31.01). Furthermore, %ΔMTV41 significantly predicted patients' recurrence-free survival (RFS) (P < 0.1). In the LN analysis, 7 LNs were classified as well-responders and 10 as poor-responders. Pre-treatment SULmax, SULpeak were significantly lower in poor-responders compared to well-responders. Post-treatment MTV50 and all percentage changes in parameters were significantly higher in the poor-responder group (all P < 0.05). Receiver operating characteristic curve (ROC) analysis indicated %ΔTLG50 had excellent predictive performance for well-responders, with an AUC of 1.000 (cut-off: -7.5). However, there was no significant correlation between the metabolic response evaluations for PTs and LNs. Conclusion: The metabolic parameters of [18F]FDG PET/CT, particularly %ΔMTV and %ΔTLG, could effectively predict well-responders among both PTs and LNs to neoadjuvant PD-L1 blockade monotherapy in LA-ESCC, which may facilitate personalized immunotherapy and serve as a stratification tool in future larger-scale studies. [ABSTRACT FROM AUTHOR]

Simple Summary: We have already demonstrated that an SBRT-escalated protocol allows for very high doses per fraction (11Gy/fraction), up to total dose up to 55Gy, which is safe and feasible in a standard LINAC-platform for patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC). In this study, we demonstrated for the first time that after neoadjuvant Cht and escalated dose SBRT, resection was indicated in 84.6% of BRPC and 20% of LAPC. Furthermore, all evaluable patients after surgery had complete or minimal disease resection (R0/R1), with objective pathological responses of 81.8% (TRS0-2). The present follow-up (FUP) was closed on 1 November 2024. The actuarial 1- and 2-year rates for freedom from local relapse as a first cause of disease failure were 92.3% (87.7–93.3%) and 79.7% (79.7–87.7%), respectively. This study shows that neoadjuvant ChT-SBRT, particularly with BED > 100, is highly effective in converting BRPC/LAPC to resectable status, providing a pathway to potentially curative surgery in a subset of patients. Objective: We demonstrated for the first time the safety and feasibility of escalating up to 55 Gy/11 Gy/fr/5fr in borderline (BRPC)/unresectable locally advanced pancreatic cancer (LAPC), using the standard LINAC platform. The aim of the present study is to assess for the first time the impact of this high-dose neoadjuvant stereotactic ablative radiotherapy (SABRT) protocol on tumor resectability and pathological responses. Materials/Methods: From June 2017 to December 2022, patients with BRPC/LAPC were treated with neoadjuvant chemotherapy (ChT) and SABRT-escalated doses of SIB at 45 Gy, 50 Gy, and up to 55 Gy (BED ≥ 100). Radiological evaluation was conducted with a CT scan 6-8 weeks post-treatment to determine resectability status based on established criteria (SAR/APA2014). Surgical decisions were made by the multidisciplinary tumor board of the participating institutions. Pathological assessments post-surgery used criteria from the College of American Pathologists (CAP), categorizing resection status as R0 (negative margins), R1 (microscopic tumor margins), and R2 (macroscopic tumor margins). Tumor response was evaluated with the Tumor Response Scoring (TRS) system, as G0 (no viable cancer cells), G1 (single cells or rare small groups), G2 (residual cancer with evident regression), and G3 (extensive residual cancer). Results: Thirty-three patients (p) were included: 39.4% (13p) BRPC/60.6% (20p) LAPC. After ChT-SABRT, 45.5% (15p) were considered resectable, with 11/13 (84.6%) BRPC and 4/20 (20%) LAPC (p < 0.0001). One patient refused surgery and other patient died of COVID sepsis. Two more patients had disseminated disease at surgery. Among the 11 patients who underwent full surgery, all patients achieved either clean margins R0: 72.7% (8p) or microscopic affected margins R1: 27.3% (3p). TRS scores were G1: 27.3% (3p), G2: 54.5% (6p), and G3: 18.2% (2p). The present follow-up (FUP) was closed on 1 November 2024 (23.55 months, range: 6–71 months). The mean freedom from local progression as the first cause of disease failure was 43.30 ± 3.09 (37.23–49.38), and the median was not reached. The actuarial 1- and 2-year rates for freedom from local relapse as a first cause of disease failure were 92.3% (87.7–93.3%) and 79.7% (79.7–87.7%), respectively. Conclusions: Neoadjuvant ChT-SABRT in LAPC improves resectability rates and induces relevant tumor regression. These promising findings should be validated by larger sample sizes and extended follow-up. [ABSTRACT FROM AUTHOR]

Purpose: The role of adjuvant chemotherapy in rectal cancer patients downstaged to ypT0-2 N0 after neoadjuvant chemoradiotherapy (CRT), and surgery is still debated. This study investigates the impact of adjuvant chemotherapy on survival outcomes in this patient population. Methods: This retrospective study analyzed hospital records of rectal cancer cases from Shefa Al Orman Cancer Hospital between January 2016 and December 2020, focusing on patients downstaged to ypT0-2 N0 after neoadjuvant CRT and surgery. Patients were divided into two groups based on whether they received adjuvant chemotherapy. Baseline characteristics, DFS, and OS were compared, and survival factors were analyzed using univariate and multivariate Cox regression. Results: Eighty-five patients met the inclusion criteria; 55 received adjuvant chemotherapy, and 30 did not. The median age was 52, but those receiving adjuvant therapy were younger (47 vs. 60 years, P = 0.006). No significant differences were observed in sex, tumor location, or pathology between groups. Although adjuvant chemotherapy showed a trend toward better 3-year DFS (89.5% vs. 81.9%, P = 0.153) and OS (88.1% vs. 84.6%, P = 0.654), these differences were not statistically significant. Univariate and multivariate analyses confirmed no significant effect of adjuvant chemotherapy on DFS or OS, nor were any other variables significantly associated with survival. Conclusion: Adjuvant chemotherapy did not significantly improve DFS or OS in rectal cancer patients downstaged to ypT0-2 N0 following neoadjuvant CRT and surgery. Further studies are needed to define the role of adjuvant therapy in this group. [ABSTRACT FROM AUTHOR]

Objective Neoadjuvant chemotherapy (NACT) has been the primary treatment method for patients with local advanced breast cancer. A pathological complete response (pCR) to therapy correlates with better overall disease prognosis. Magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) have been widely used to monitor the response to NACT in breast cancer. The aim of this study was to assess tumor response to NACT by MRI and PET/CT, to determine which imaging modality is more accurate in detecting tumor response post NACT in breast cancer. Materials and Methods A retrospective review of our database revealed 34 women with breast cancer thathad MRI and PET/CT performed prior to and after NACT, followed by definitive surgery. For response assessment, we calculated the difference in maximum diameter of the tumor in MRI and difference in standard uptake values in PET/CT. The correspondence rate between the imaging modalities and pCR were calculated. For the prediction of pCR, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy where analyzed. Results The assessment of tumor response to NACT showed 11cases with pCR (32%), 15 pathological partial response (44%) and eight pathological no response (24%). The correspondence rate between MRI and pathological response was 50% (17/34), compared to 65% (22/34) for PET/CT. For prediction of pCR, MRI showed higher specificity compared to PET/CT (78.2% vs. 73.9%, p = 0.024), while the accuracy of PET/CT was significantly higher (79.4% vs. 70.5%, p = 0.004). PET/CT also had a higher NPV compared to MRI (94.4% vs. 78.2%, p = 0.002). There were no differences in terms of sensitivity and PPV between MRI and PET/CT. Conclusion Compared to MRI, PET/CT was more likely to correlate with the pathological response after NACT. For the prediction of pCR, PET/CT proved to be a more accurate imaging modality to monitor response after NACT than MRI. Keywords:Breast cancer, MRI, neoadjuvant chemotherapy, pathological response, PET/CT: [ABSTRACT FROM AUTHOR]

Abstract Background The study aimed to investigate the predictive value of delta-radiomics derived from computed tomography (CT) for pathological complete response (pCR) to neoadjuvant immunochemotherapy (NICT) among patients with esophageal squamous cell carcinoma (ESCC), helping clinicians determine whether to modify the neoadjuvant treatment strategy, proceed to surgery, or forgo surgery altogether. Methods A total of 140 ESCC patients from two institutions (Database 1 = 93; Database 2 = 47) who underwent NICT and surgery were retrospectively included in the study. The training set consisted of patients from Database 1, while the testing set included patients from Database 2. All patients underwent contrast-enhanced CT scans before the start of the treatment and prior to the operation. The delta-radiomics features were calculated as the relative net change of radiomics features between the two-time points. Feature selection was conducted using Pearson correlation analysis, intraclass correlation coefficients, and the fivefold cross-validation with least absolute shrinkage and selection analysis. Four models were established, comprising a clinical model, a pre-treatment radiomics model, a delta-radiomics model, and a mixed model. Area under the curve (AUC) and decision curve analysis were used to assess the performance and the clinical value of the models. Results Less than half of the tumors (40/140, 28.6%) showed pCR following NICT. The delta-radiomics model displayed AUC of 0.827 and 0.790 in the training and testing set for predicting pCR, which was superior to the clinical model based on age and clinical tumor node metastasis (cTNM) stage (0.758 and 0.615) and the pre-treatment radiomics model (0.787 and 0.621). Furthermore, the delta-radiomics model demonstrated a more excellent AUC value in the testing set than the mixed model (0.847 and 0.719), which integrated clinical and delta-radiomics features. Conclusions The delta-radiomics model exhibited better diagnostic performance in preoperative prediction of pCR for NICT in ESCC patients compared to the clinical, pre-treatment radiomics, and mixed models.

Introduction: Breast cancer is the most common malignancy in women, and it is the second leading cause of malignancy-related mortality in women after lung cancer. Locally advanced breast cancer is a clinically heterogeneous group with a broad spectrum. Neoadjuvant chemotherapy (NAC) is the standard treatment at this stage. The present study aimed to evaluate the efficacy of NAC in terms of histopathologic molecular subtypes. Methods: The study included 183 patients receiving NAC. Patients were studied in three groups: Luminal tumors, human epidermal growth factor receptor-2 (HER-2)-positive tumors, and triple-negative tumors based on the expressed receptor status. In our retrospective review, we only examined pathological complete response (pCR) based on breast tumor shrinkage before and after chemotherapy. In this study, we evaluated factors affecting pathologic complete response in patients receiving NAC. Results: According to breast cancer subtypes based on biopsy results, pCR developed in 8 of 20 patients with triple-negative tumors (40%), 24 of 61 patients with HER-2-positive tumors (39.3%), and 22 of 102 patients with luminal tumors (21.5%) (p=0.030). The pCR rate was available in 5 of 40 patients with lymphovascular invasion (LVI) (12.5%) and 49 of 143 patients without LVI (34.2%) (p=0.008). pCR was available in 1 of 16 patients with perineural invasion (PNI) (6.6%) and 53 of 168 patients without PNI (31.5%) (p=0.043). PCR was available in 2 of 25 patients with extracapsular lymph node invasion (8%) and in 52 of 158 patients without extracapsular lymph node invasion (32.9%) (p=0.011). Conclusion: The NAC pCR rate of hormone-positive tumors was lower than that of hormone-negative tumors in breast cancer. This finding was related to the biological response of the tumor in heterogeneous breast cancer.

Abstract Background Achieving a pathological complete response (pCR) after neoadjuvant therapy (NAT) is considered to be a critical factor for a favourable prognosis in breast cancer. However, discordant pathological complete response (DpCR), characterised by isolated responses in the breast or axillary, represents an intermediate pathological response category between no response and complete response. This study aims to investigate predictive factors and develop models based on peripheral blood inflammatory indexes to more accurately predict NAT outcomes. Method A total of 789 eligible patients were enrolled in this retrospective study. The patients were randomized into training and validation cohort according to a 7:3 ratio. Lasso and uni/multivariable logistic regression analysis were applied to identify the predictor variables. Two Nomograms combining clinico-pathologic features and peripheral blood inflammatory indexes were developed. Result Molecular Subtype, HALP, P53, and FAR were used to construct the predictive models for traditional non pCR (T-NpCR) and total-pCR (TpCR). The T-NpCR group was divided into DpCR and non pCR (NpCR) subgroups to construct a new model to more accurately predict NAT outcomes. cN, HALP, FAR, Molecular Subtype, and RMC were used to construct the predictive models for NpCR and DpCR. The receiver operating characteristic (ROC) curves indicate that the model exhibits robust predictive capacity. Clinical Impact Curves (CIC) and Decision Curve Analysis (DCA) indicate that the models present a superior clinical utility. Conclusion HALP and FAR were identified as peripheral blood inflammatory index predictors for accurately predicting NAT outcomes.

Background: Complete pathological response to neoadjuvant treatment (NAT) in breast cancer is associated with prolonged survival. Compared to other breast cancer immunophenotypes, luminal tumors are the least chemosensitive with low rates of pathological response within this molecular subtype. Thus, finding predictors of response in this subset remains challenging. The emerging concept of low human epidermal growth factor receptor 2 (HER2) expression has led to a repurpose of the current prognostic system. Little is known about its correlation with response to NAT. Objectives: This study aims to evaluate predictors of response in early-stage luminal breast cancer receiving neoadjuvant chemotherapy. Design: A total of 252 luminal patients who received NAT were retrospectively assessed in this cohort study. Methods: We analyzed the correlation of ki67 and HER2 low expression with the rate of pathologic response. Using ki67 as a continuous variable and applying the receiver operating characteristic curves method. Results: We identified that in patients with a ki67 expression level >37%, the probability of having a complete pathological response was 4.80 times higher (odds ratio = 4.80, 95% confidence interval: 1.92–12.04). In Her2-low breast cancer patients, Her2 expression did not correlate with a better response rate. Conclusion: In our study, a ki67 expression value greater than 37% constitutes a predictive biomarker of pathological complete response in the subgroup of patients with luminal B tumors and could be considered, therefore, an indicator for treatment decisions in this subgroup. [ABSTRACT FROM AUTHOR]

Background: The study aimed to investigate the predictive value of delta-radiomics derived from computed tomography (CT) for pathological complete response (pCR) to neoadjuvant immunochemotherapy (NICT) among patients with esophageal squamous cell carcinoma (ESCC), helping clinicians determine whether to modify the neoadjuvant treatment strategy, proceed to surgery, or forgo surgery altogether. Methods: A total of 140 ESCC patients from two institutions (Database 1 = 93; Database 2 = 47) who underwent NICT and surgery were retrospectively included in the study. The training set consisted of patients from Database 1, while the testing set included patients from Database 2. All patients underwent contrast-enhanced CT scans before the start of the treatment and prior to the operation. The delta-radiomics features were calculated as the relative net change of radiomics features between the two-time points. Feature selection was conducted using Pearson correlation analysis, intraclass correlation coefficients, and the fivefold cross-validation with least absolute shrinkage and selection analysis. Four models were established, comprising a clinical model, a pre-treatment radiomics model, a delta-radiomics model, and a mixed model. Area under the curve (AUC) and decision curve analysis were used to assess the performance and the clinical value of the models. Results: Less than half of the tumors (40/140, 28.6%) showed pCR following NICT. The delta-radiomics model displayed AUC of 0.827 and 0.790 in the training and testing set for predicting pCR, which was superior to the clinical model based on age and clinical tumor node metastasis (cTNM) stage (0.758 and 0.615) and the pre-treatment radiomics model (0.787 and 0.621). Furthermore, the delta-radiomics model demonstrated a more excellent AUC value in the testing set than the mixed model (0.847 and 0.719), which integrated clinical and delta-radiomics features. Conclusions: The delta-radiomics model exhibited better diagnostic performance in preoperative prediction of pCR for NICT in ESCC patients compared to the clinical, pre-treatment radiomics, and mixed models. [ABSTRACT FROM AUTHOR]

Background and Objectives: The HALP (Haemoglobin, Albumin, Lymphocyte and Platelet) score is used to predict the prognosis of different types of cancer. This study aimed to investigate the role of the HALP score in predicting pathological response in early-stage gastric cancer patients. Materials and Methods: This retrospective cohort study was conducted on 118 patients diagnosed with early-stage gastric cancer and subjected to perioperative (FLOT) treatment between 2018 and 2023. The role of the HALP score in predicting the pathological response to perioperative treatment in patients was investigated. Results: The mean age of the 118 patients included in the study was 61.3 ± 11.1 (min = 23; max = 86). In the ROC analysis, the optimum cut-off value for the HALP score in pathological response classification was found to be 28.9 (AUC = 0.710, sensitivity = 56.7%, specificity = 80%, PPV = 86.79%, NPV = 46.15%). The pathological response rate was 69% in all patients, 87% in patients with a HALP score ≥ 28.9, and 52% in patients with a HALP score < 28.9 (p < 0.001). The probability of pathological response is 6.5 times higher in patients with a HALP score ≥ 28.9. In the Fagan nomogram, when the HALP score was ≥28.9, our pathological response probability estimate (post-test response probability) was found to increase to 64.8% (Positive Likelihood Ratio = 3, Negative Likelihood Ratio = 0.53). In patients with HALP scores ≥ 28.9 and <28.9, progression rates were 16.7% and 47.8%, respectively (p < 0.001), and median survival times were 45.4 and 30.6 months (p < 0.001). Conclusions: The HALP score is a useful and easily accessible score for determining pathological responses in patients with locally advanced gastric cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Objective: Neoadjuvant chemotherapy (NACT) is currently a standard therapeutic approach to downstage the locally advanced breast cancer. This study aimed to 1) Evaluate the post NACT histopathological changes in the mastectomy specimens and lymph nodes, 2) Compare the immuno-histochemistry profiles of hormone receptor status ER, PR and HER2/NEU before and after NACT, 3) Categorize the patients according to the pathological response. Methods: Hospital based prospective study was conducted on 50 cases, diagnosed as carcinoma breast on trucut biopsies and assessed for ER, PR and HER2/NEU receptor status. Following NACT, modified radical mastectomy specimens were evaluated for histopathological changes, residual tumor and patients were categorized according to pathological response. The specimens with residual tumor were again subjected to ER, PR and HER2/NEU receptor status. Then comparison of ER, PR and HER2/NEU status was done between pre and post NACT specimens which showed residual tumor. Results: Histopathological changes observed were DCIS (14%), inflammation (88%), necrosis (74%), fibrosis (90%), calcification (12%) and LVI (20%). Among 50 cases, 14% showed pathological complete response, 48% showed pathological partial response and 38% showed pathological no response. Among 43 cases, comparison of ER, PR and HER2/NEU status between pre and post NACT cases documented a statistically significant loss of ER expression (p=0.020) and PR expression (p= 0.014) while no significant difference was observed in HER2/NEU expression. Conclusions: This study highlights the NACT induced histopathological, hormonal receptor-ER, PR and HER2/NEU changes along with assessment of pathological response to therapy which provides valuable prognostic information and helps in directing the effective hormonal/targeted treatment. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer is the most common malignancy in women, and it is the second leading cause of malignancy-related mortality in women after lung cancer. Locally advanced breast cancer is a clinically heterogeneous group with a broad spectrum. Neoadjuvant chemotherapy (NAC) is the standard treatment at this stage. The present study aimed to evaluate the efficacy of NAC in terms of histopathologic molecular subtypes. Methods: The study included 183 patients receiving NAC. Patients were studied in three groups: Luminal tumors, human epidermal growth factor receptor-2 (HER-2)-positive tumors, and triple-negative tumors based on the expressed receptor status. In our retrospective review, we only examined pathological complete response (pCR) based on breast tumor shrinkage before and after chemotherapy. In this study, we evaluated factors affecting pathologic complete response in patients receiving NAC. Results: According to breast cancer subtypes based on biopsy results, pCR developed in 8 of 20 patients with triple-negative tumors (40%), 24 of 61 patients with HER-2-positive tumors (39.3%), and 22 of 102 patients with luminal tumors (21.5%) (p=0.030). The pCR rate was available in 5 of 40 patients with lymphovascular invasion (LVI) (12.5%) and 49 of 143 patients without LVI (34.2%) (p=0.008). pCR was available in 1 of 16 patients with perineural invasion (PNI) (6.6%) and 53 of 168 patients without PNI (31.5%) (p=0.043). PCR was available in 2 of 25 patients with extracapsular lymph node invasion (8%) and in 52 of 158 patients without extracapsular lymph node invasion (32.9%) (p=0.011). Conclusion: The NAC pCR rate of hormone-positive tumors was lower than that of hormone-negative tumors in breast cancer. This finding was related to the biological response of the tumor in heterogeneous breast cancer. [ABSTRACT FROM AUTHOR]

Objective: This meta‐analysis aims to evaluate the efficacy and safety of antiprogressive disease (PD)‐(L)1‐based neoadjuvant therapy in head and neck squamous cell carcinoma (HNSCC) patients and identify potential prognostic biomarkers. Data Sources: Databases were systematically searched for prospective clinical trials evaluating the efficacy and safety of anti‐PD‐(L)1‐based neoadjuvant therapy for HNSCC before January 12, 2024. Review Methods: We estimated the efficacy and safety of neoadjuvant immune checkpoint inhibitors. Subgroup and sensitivity analyses were further performed. Results: A total of 570 patients from 20 studies were included. The pooled major pathological response (MPR), pathological complete response (pCR), and partial pathological response (PPR) rates were 30.7%, 15.3%, and 68.2%, respectively. Surgical complications, surgical delayed rate, all grade treatment‐related adverse effects (TRAEs) and ≥Grade 3 TRAEs were 0.6%, 0.3%, 82.6%, and 9.7%, respectively. Best MPR or pCR rate was detected in patients receiving neoadjuvant anti‐PD‐(L)1 therapy + radiotherapy (with MPR rate of 75.5% and pCR rate of 51.1%) and neoadjuvant anti‐PD‐(L)1 therapy + chemotherapy groups (with MPR rate of 57.5% and pCR rate of 26.7%). No differences were detected in subgroups stratified by neoadjuvant treatment cycles, human papillomavirus (HPV) status, and tumor location. Patients with baseline Combined Positive Score (CPS) ≥ 20 have higher MPR and pCR rates compared to patients with CPS < 20. High Tumor Cell Proportion Score was also associated with MPR and pCR. Objective response rate is a strong predictor of MPR (odds ratio [OR] = 7.78, 95% confidence interval [CI] = 3.20%‐18.91%) and pCR (OR = 3.24, 95% CI = 1.40%‐7.48%). Conclusion: Anti‐PD‐(L)1‐based neoadjuvant therapy was effective and safe for HNSCC patients. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is the most commonly diagnosed malignant tumor in women. The disease and its subsequent treatment pose a serious burden on the quality of life of patients. Neoadjuvant chemotherapy (NAC) has become one of the crucial strategies for the management of BC. Since the identification of the vitamin D receptor (VDR) in mammary tissues, extensive mechanistic research has been conducted on its function. The expression of VDR in BC cells and the tumor microenvironment could be a new prognostic factor for BC after NAC. Patients and Methods: This observational, single-center study compared data from clinical and histopathological records of 111 female subjects with the expression of VDR in different cellular and tissue components of breast specimens obtained from surgery after NAC. VDR expression was evaluated using an immunoreactive score assigned after immunohistochemistry. Intergroup comparisons and logistic regression were used to identify associations between VDR expression and clinicopathological features of BC. Results: We found that the expression of VDR is associated with various clinical features (i.e., age, menopausal status, and NAC cycle number) and characteristics of prognostic significance, such as residual cancer burden class. Logistic regression analysis revealed that the expression of VDR in the nuclei and cytoplasm of surrounding normal mammary cells predicted vascular invasion and lymph node involvement. Conclusions: The expression of VDR in tumor cells and their microenvironment is related to the clinicopathological characteristics of BC after NAC. [ABSTRACT FROM AUTHOR]

Background: Achieving a pathological complete response (pCR) after neoadjuvant therapy (NAT) is considered to be a critical factor for a favourable prognosis in breast cancer. However, discordant pathological complete response (DpCR), characterised by isolated responses in the breast or axillary, represents an intermediate pathological response category between no response and complete response. This study aims to investigate predictive factors and develop models based on peripheral blood inflammatory indexes to more accurately predict NAT outcomes. Method: A total of 789 eligible patients were enrolled in this retrospective study. The patients were randomized into training and validation cohort according to a 7:3 ratio. Lasso and uni/multivariable logistic regression analysis were applied to identify the predictor variables. Two Nomograms combining clinico-pathologic features and peripheral blood inflammatory indexes were developed. Result: Molecular Subtype, HALP, P53, and FAR were used to construct the predictive models for traditional non pCR (T-NpCR) and total-pCR (TpCR). The T-NpCR group was divided into DpCR and non pCR (NpCR) subgroups to construct a new model to more accurately predict NAT outcomes. cN, HALP, FAR, Molecular Subtype, and RMC were used to construct the predictive models for NpCR and DpCR. The receiver operating characteristic (ROC) curves indicate that the model exhibits robust predictive capacity. Clinical Impact Curves (CIC) and Decision Curve Analysis (DCA) indicate that the models present a superior clinical utility. Conclusion: HALP and FAR were identified as peripheral blood inflammatory index predictors for accurately predicting NAT outcomes. [ABSTRACT FROM AUTHOR]

Background and aim: Docetaxel, oxaliplatin, leucovorin and 5-fluorouracil (FLOT) may improve overall survival (OS) in patients with locally advanced gastric and gastroesophageal cancer. Our study aims to determine the pathological response in these patients with the FLOT chemotherapy in the Neoadjuvant setting. This is the first study conducted in our country. Methods: We conducted a retrospective cross-sectional study from March 2018 to December 2020. After ethical review committee approval, all patients who fulfilled the inclusion criteria and received treatment at our tertiary care center were included in the study. SPSS version 22 was used for data analysis. Frequencies and percentages were calculated for categorical. Values were presented as mean ± standard deviation (SD) for continuous variables. The chi-square test was used to determine the difference between categorical variables. A p-value of ≤0.05 was considered the level of significance. Kaplan- Meier curves were used to calculate survival analysis. Results: Out of 41, 35 patients with locally advanced resectable gastric or gastroesophageal adenocarcinoma were included in our study analysis. The entire cohort had a male predominance, with a mean age of 59. All patients received neoadjuvant FLOT. Pathological treatment response achieved was 77%, of which 66% had partial and 11% had complete response. There is a significant association of pathological response with age, gender, stage, grade, co-morbid and number of chemotherapy cycles received (p-value =<0.05). The OS was 80% with the mean OS was 2.6 years (31 months). Conclusion: Our study shows comparable response rates to other studies conducted internationally. Our findings confirm that FLOT is an effective and well-tolerated perioperative regimen with reasonable response rates in the Pakistani population. A more extensive longitudinal study would ensure these preliminary results in the local patient population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BACKGROUND: Neoadjuvant chemotherapy therapy ( NACT) has emerged as an integrated therapeutic approach to treat locally advanced breast cancer in order to down stage the tumour and to assess tumour response to chemotherapy. The aims of this study were to estimate the incidence of complete and partial pathological response in patients undergoing NACT for breast cancer and to evaluate the clinico pathological parameters associated with pathological response. MATERIALS AND METHODS: The study included breast cancer specimens from patients who had received NACT. The pathological response to NACT was assessed by the AJCC protocol and the morphological features associated with NACT were recorded. The clinicopathological parameters associated with complete pathological response were also studied. The association between the clinicopathological paramaters and pathological response was studies using Chi square and Fisher exact tests. RESULTS: There were a total of 50 women who underwent surgery for breast cancer following NACT. The mean age was 56.5 years. The majority (59.1%) belonged to stage IIIB followed by Stage III A ( 30.6%). 73.4% of cases showed clinical partial response, 14.2 % showed no response and 12.2 percent showed Pathological Complete Response (pCR). ER and PR negative and Her 2 positive status were the parameters significantly associated with pCR. CONCLUSIONS: Pathological evaluation is the most reliable method to assess response to NACT in breast cancer patients which may further influence management decisions. This study showed a much lower frequency of pCR when compared to other Indian studies. It is recommended that all patients who are treated with NACT undergo prior core needle biopsy with hormone receptor and Her 2 testing as they may have a bearing on pCR.

Abstract Background: The aim of this study is to investigate the added value of combining tumour blood flow (BF) and metabolism parameters, including texture features, with clinical parameters to predict, at baseline, the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in patients with newly diagnosed breast cancer (BC). Methods: One hundred and twenty-eight BC patients underwent a 18F-FDG PET/CT before any treatment. Tumour BF and metabolism parameters were extracted from first-pass dynamic and delayed PET images, respectively. Standard and texture features were extracted from BF and metabolic images. Prediction of pCR was performed using logistic regression, random forest and support vector classification algorithms. Models were built using clinical (C), clinical and metabolic (C+M) and clinical, metabolic and tumour BF (C+M+BF) information combined. Algorithms were trained on 80% of the dataset and tested on the remaining 20%. Univariate and multivariate features selections were carried out on the training dataset. A total of 50 shuffle splits were performed. The analysis was carried out on the whole dataset (HER2 and Triple Negative (TN)), and separately in HER2 (N=76) and TN (N=52) tumours. Results: In the whole dataset, the highest classification performances were observed for C+M models, significantly (p-value

Abstract 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.

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. [ABSTRACT FROM AUTHOR]

Introduction: Transarterial chemoembolization combined with lenvatinib and PD-1 inhibitor (triple therapy) has displayed encouraging clinical outcomes for unresectable hepatocellular carcinoma (uHCC). We aimed to explore the prognostic value of pathological response (PR) in patients with initially uHCC who underwent conversion surgery following triple therapy and identify predictors of major pathological response (MPR). Methods: A total of 76 patients with initially uHCC who underwent conversion surgery following triple therapy were retrospectively analyzed. PR was calculated as the proportion of nonviable tumor cell surface area of the whole tumor bed surface area. MPR was identified when PR was ≥90%. Pathological complete response (pCR) was defined as the absence of viable tumor cells. Results: MPR and pCR were identified in 53 (69.7%) and 25 (32.9%) patients, respectively. The 1- and 2-year overall survival in patients with MPR were significantly higher than in those without MPR (100.0% and 91.3% vs. 67.7% and 19.4%; p < 0.001). The corresponding recurrence-free survival was also improved in patients with MPR compared to those without (75.9% and 50.8% vs. 22.3% and 11.2%; p < 0.001). Similar results were observed among patients with pCR and those without. Patients who achieved MPR without pCR exhibited survival rates comparable to those of patients who achieved pCR. Baseline neutrophil-to-lymphocyte ratio ≥2.6 (p = 0.016) and preoperative alpha-fetoprotein level ≥400 ng/mL (p = 0.015) were independent predictors of MPR. Conclusion: The presence of MPR or pCR could improve prognosis in patients with initially uHCC who underwent conversion surgery following triple therapy. The PR may become a surrogate marker for predicting the prognosis of these patients. Plain Language Summary: The combination of transarterial chemoembolization, lenvatinib, and PD-1 inhibitor is an efficacious conversion therapy for uHCC. In this multicenter retrospective study, we discovered that PR was associated with the prognosis of patients who underwent conversion surgery. Predictors of MPR included neutrophil-to-lymphocyte ratio and alpha-fetoprotein levels. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer continues to be the leading cause of cancer-related deaths worldwide. Many patients present advanced disease at the time of the diagnosis. Neoadjuvant therapy aims to reduce the tumor stage and improve the operability of patients, and simultaneously leads to tumor regression. The tumor regression grade reflects the degree of pathological response to therapy. Thus, we conducted this study to identify the predictors for pathologic response after neoadjuvant treatment followed by surgery. The second goal of our research was to find the relationship between survival and tumor regression. Our study revealed that the histology of the primary tumor, lymph node size in the preoperative CT scan (>1.7 cm), and absolute tumor size reduction after neoadjuvant treatment (>2.6 cm) independently predict the effectiveness of tumor regression. Age > 70 years, extended resection > one lobe, and tumor recurrence or metastasis were identified as significant independent predictors of reduced overall survival. Our study aimed to identify predictors for the effectiveness of tumor regression in lung cancer patients undergoing neoadjuvant treatment and cancer resections. Patients admitted between 2016 and 2022 were included in the study. Based on the histology of the tumor, patients were categorized into a lung adenocarcinoma group (LUAD) and squamous cell carcinoma group (SQCA). Ninety-five patients with non-small-cell lung cancer were included in the study. A total of 58 (61.1%) and 37 (38.9%) patients were included in the LUAD and SQCA groups, respectively. Additionally, 9 (9.5%), 56 (58.9%), and 30 (31.6%) patients were categorized with a tumor regression score of I, II, and III, respectively. In multivariable analyses, histology of the primary tumor (SQCA), lymph node size in the preoperative CT scan (>1.7 cm), and absolute tumor size reduction after neoadjuvant treatment (>2.6 cm) independently predict effectiveness of tumor regression (OR [95% confidence interval, p-value] of 6.88 [2.40–19.77, p < 0.0001], 3.13 [1.11–8.83, p = 0.0310], and 3.76 [1.20–11.81, p = 0.0233], respectively). Age > 70 years, extended resection > one lobe, and tumor recurrence or metastasis were identified as significant independent predictors of reduced overall survival. Assessment of tumor size before and after neoadjuvant treatment might help to identify high-risk patients with decreased survival and to improve patient management and care. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to investigate the added value of combining tumour blood flow (BF) and metabolism parameters, including texture features, with clinical parameters to predict, at baseline, the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in patients with newly diagnosed breast cancer (BC). Methods: One hundred and twenty-eight BC patients underwent a 18F-FDG PET/CT before any treatment. Tumour BF and metabolism parameters were extracted from first-pass dynamic and delayed PET images, respectively. Standard and texture features were extracted from BF and metabolic images. Prediction of pCR was performed using logistic regression, random forest and support vector classification algorithms. Models were built using clinical (C), clinical and metabolic (C+M) and clinical, metabolic and tumour BF (C+M+BF) information combined. Algorithms were trained on 80% of the dataset and tested on the remaining 20%. Univariate and multivariate features selections were carried out on the training dataset. A total of 50 shuffle splits were performed. The analysis was carried out on the whole dataset (HER2 and Triple Negative (TN)), and separately in HER2 (N=76) and TN (N=52) tumours. Results: In the whole dataset, the highest classification performances were observed for C+M models, significantly (p-value<0.01) higher than C models and better than C+M+BF models (mean balanced accuracy of 0.66, 0.61, and 0.64 respectively). For HER2 tumours, equal performances were noted for C and C+M models, with performances higher than C+M+BF models (mean balanced accuracy of 0.64, and 0.61 respectively). Regarding TN tumours, the best classification results were reported for C+M models, with better performances than C and C+M+BF models but not significantly (mean balanced accuracy of 0.65, 0.63, and 0.62 respectively). Conclusion: Baseline clinical data combined with global and texture tumour metabolism parameters assessed by 18F-FDG PET/CT provide a better prediction of pCR after NAC in patients with BC compared to clinical parameters alone for TN, and HER2 and TN tumours together. In contrast, adding BF parameters to the models did not improve prediction, regardless of the tumour subgroup analysed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BackgroundA meta-analysis study was done to figure out how to predict the prognosis of people with resectable non-small-cell lung cancer (NSCLC) who had a significant pathological response following neoadjuvant immunotherapy.MethodsUp until August 2024, a comprehensive literature study was completed, and 2,386 connected studies were revised. The 35 selected studies included 3,118 resectable non-small-cell lung tumor participants at the beginning of the study. Using dichotomous techniques and a fixed or random model, the odds ratio (OR) and 95% confidence intervals (CIs) were used to assess the prediction using significant pathological response following neoadjuvant immunotherapy in resectable NSCLC.ResultsIndividuals with resectable NSCLC had significantly higher major pathological response when comparing neoadjuvant chemo-immunotherapy to neoadjuvant chemotherapy (OR, 5.07; 95% CI, 4.09–6.27, p

BackgroundBreast cancer (BC) is the most commonly diagnosed malignant tumor in women. The disease and its subsequent treatment pose a serious burden on the quality of life of patients. Neoadjuvant chemotherapy (NAC) has become one of the crucial strategies for the management of BC. Since the identification of the vitamin D receptor (VDR) in mammary tissues, extensive mechanistic research has been conducted on its function. The expression of VDR in BC cells and the tumor microenvironment could be a new prognostic factor for BC after NAC.Patients and MethodsThis observational, single-center study compared data from clinical and histopathological records of 111 female subjects with the expression of VDR in different cellular and tissue components of breast specimens obtained from surgery after NAC. VDR expression was evaluated using an immunoreactive score assigned after immunohistochemistry. Intergroup comparisons and logistic regression were used to identify associations between VDR expression and clinicopathological features of BC.ResultsWe found that the expression of VDR is associated with various clinical features (i.e., age, menopausal status, and NAC cycle number) and characteristics of prognostic significance, such as residual cancer burden class. Logistic regression analysis revealed that the expression of VDR in the nuclei and cytoplasm of surrounding normal mammary cells predicted vascular invasion and lymph node involvement.ConclusionsThe expression of VDR in tumor cells and their microenvironment is related to the clinicopathological characteristics of BC after NAC.

Abstract Background The efficacy of neoadjuvant chemo-immunotherapy (NAT) in esophageal squamous cell carcinoma (ESCC) is challenged by the intricate interplay within the tumor microenvironment (TME). Unveiling the immune landscape of ESCC in the context of NAT could shed light on heterogeneity and optimize therapeutic strategies for patients. Methods We analyzed single cells from 22 baseline and 24 post-NAT treatment samples of stage II/III ESCC patients to explore the association between the immune landscape and pathological response to neoadjuvant anti-PD-1 combination therapy, including pathological complete response (pCR), major pathological response (MPR), and incomplete pathological response (IPR). Results Single-cell profiling identified 14 major cell subsets of cancer, immune, and stromal cells. Trajectory analysis unveiled an interesting link between cancer cell differentiation and pathological response to NAT. ESCC tumors enriched with less differentiated cancer cells exhibited a potentially favorable pathological response to NAT, while tumors enriched with clusters of more differentiated cancer cells may resist treatment. Deconvolution of transcriptomes in pre-treatment tumors identified gene signatures in response to NAT contributed by specific immune cell populations. Upregulated genes associated with better pathological responses in CD8 + effector T cells primarily involved interferon-gamma (IFNγ) signaling, neutrophil degranulation, and negative regulation of the T cell apoptotic process, whereas downregulated genes were dominated by those in the immune response-activating cell surface receptor signaling pathway. Natural killer cells in pre-treatment tumors from pCR patients showed a similar upregulation of gene expression in response to IFNγ but a downregulation of genes in the neutrophil-mediated immunity pathways. A decreased cellular contexture of regulatory T cells in ESCC TME indicated a potentially favorable pathological response to NAT. Cell–cell communication analysis revealed extensive interactions between CCL5 and its receptor CCR5 in various immune cells of baseline pCR tumors. Immune checkpoint interaction pairs, including CTLA4-CD86, TIGIT-PVR, LGALS9-HAVCR2, and TNFSF4-TNFRSF4, might serve as additional therapeutic targets for ICI therapy in ESCC. Conclusions This pioneering study unveiled an intriguing association between cancer cell differentiation and pathological response in esophageal cancer patients, revealing distinct subgroups of tumors for which neoadjuvant chemo-immunotherapy might be effective. We also delineated the immune landscape of ESCC tumors in the context of clinical response to NAT, which provides clinical insights for better understanding how patients respond to the treatment and further identifying novel therapeutic targets for ESCC patients in the future.

Abstract 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 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

Purpose: Patients with locally advanced rectal cancer (LARC) who underwent total neoadjuvant therapy (TNT) showed an increase in the percentage of complete pathological response (pCR). The purpose of this study was to determine the correlation between Ki-67, tumor-infiltrating lymphocytes (TIL), and TNT in LARC patients. Method: In total, one hundred fifty-nine patients with LARC were included in this prospective study. The international working group was used to categorize the TIL into three groups based on the percentage and density of staining: group 0 (0–10%), group 1 (11–59%), and group 2 (≥ 60%). Ki-67 expression was classified as low (≤ 50%) or high (> 50%). Result: Most patients had tumor grade III (74.2%) and T2–T3 (78.6%). Lymph node involvement (48.7%) and tumor size ≥ 3 cm were detected in approximately half of the patients. Forty-four percent of patients had a high Ki-67 index; 15.7% of patients belonged to group 1, and 21.4% belonged to group 2. pCR was detected in 18.2% of the patients. TIL and Ki-67 levels were significantly correlated with pCR (p = 0.001 and 0.003 for multivariate analysis and 0.001 and 0.03 for univariate analysis, respectively). Conclusion: There was a statistically significant correlation between Ki-67, TIL, and pCR following TNT protocol, which may help maximize the therapeutic outcome. [ABSTRACT FROM AUTHOR]

Background: The purposes of neoadjuvant chemotherapy are to tumor size to improve the tumor removal rate, extend survival, and prevent metastasis. In this study, the importance of CRP/albumin ratio and CEA/albumin ratio in the prediction of neoadjuvant treatment response in gastric cancer patients was evaluated. Methods: This study retrospectively included 135 gastric cancer patients who received neoadjuvant chemotherapy at Çukurova University Balcalı Hospital between January 2018 and December 2023. Preoperative CRP/albumin and CEA/albumin ratios were compared according to treatment response and multivariate logistic regression analysis was performed to determine the potential importance of these ratios in predicting pathological response. Results: The mean age of the 135 patients was 58.79 ± 10.83 (min = 26–max = 78). The CRP/albumin and CEA/albumin ratios were found to be significantly lower in patients who did not respond to neoadjuvant therapy. Each 1-unit increase in the CRP/albumin ratio was associated with a 1.16-fold decrease in the odds of pathological complete response to neoadjuvant therapy. Both CRP/albumin and CEA/albumin ratios were found to be significant in distinguishing neoadjuvant therapy response. The optimal cut-off value was 2.74 for the CRP/albumin ratio (sensitivity = 60%, specificity = 78.4%) and 1.40 for the CEA/albumin ratio (sensitivity = 74.2%, specificity = 67.6%). Values below these cut-off points favored neoadjuvant therapy response. Pathological complete response to neoadjuvant therapy was 4.75 times higher in patients with a CRP/albumin ratio below 2.74 and 5.14 times higher in patients with a CEA/albumin ratio below 1.40. Conclusions: Findings demonstrate that in patients with locally advanced gastric cancer receiving neoadjuvant treatment, CRP/Albumin and CEA/Albumin ratios are significant markers of pathological response. [ABSTRACT FROM AUTHOR]

Background: There is an interest in performing de-escalating axillary surgery after neoadjuvant chemotherapy (NAC). However, the significance of residual axillary node disease after NAC has not been well studied. Objectives: To investigate the pathological residual axillary lymph node tumor burden (ypN) of patients with initial clinical nodal stage cN0-1 breast cancer after NAC and determine its prognostic value. Design: Initial cN0-1 breast cancer patients who received NAC followed by axillary surgery at the First Hospital of Jilin University and the First Affiliated Hospital of Xi'an Jiaotong University between January 2011 and December 2019 were included. Methods: Survival outcomes were compared according to different clinical and pathological stage and nodal response to NAC. The main outcomes were disease-free survival (DFS) and overall survival (OS). Factors associated with survival were defined by Cox regression analysis. Results: A total of 911 patients were included, among whom 260 had cN0 and 651 had cN1 tumors. After NAC, 410 patients were ypN0, and another 501 were ypN+. The median follow-up time was 63 months. There was no significant difference in DFS or OS between the cN0 and cN1 groups in hormone receptor positive (HR+)/human epidermal growth factor receptor 2 positive (HER2+) and HR−/HER2− subtypes; instead, ypN status was significantly related to DFS and OS. In HR+/HER2− subtype, both cN and ypN stages did not show significant survival differences, but the ypN number and the nodal response to NAC showed significant prognostic value (p < 0.05). Among HR−/HER2+ patients, all cN status, ypN status, ypN number, and nodal response were significantly associated with survival (p < 0.05). Furthermore, tumor biology, axillary surgery, ypN status, pathological tumor size, and radiotherapy were independent prognostic factors for DFS and OS. Conclusion: The ypN status after NAC provide more prognostic information than the initial cN stage in cN0-1 patients, and the surgical axillary staging after NAC may have high clinical value. [ABSTRACT FROM AUTHOR]

Background: The study aimed to investigate the efficacy and survival outcomes of neoadjuvant chemotherapy combined with programmed cell death protein 1 (PD-1) blockade (neoadjuvant chemoimmunotherapy) for patients with resectable head and neck squamous cell carcinoma (HNSCC). Methods: A retrospective analysis was conducted. Patients with initially diagnosed, resectable HNSCCs who received the neoadjuvant chemoimmunotherapy and radical surgery were included. Correlation analysis between patients' clinical characteristics and pathological responses, and survival analysis were performed. Results: A total of 79 patients were included. The majority of patients (55, 69.6%) were diagnosed at locally advanced stages and most of them (58, 73.4%) had tumor located at the oral cavity. Nearly half of patients (35, 44.3%) received two cycles of neoadjuvant chemoimmunotherapy and the rest had three or more cycles. The R0 resection rate was 98.7%. In the pathological evaluation, 53.1% of patients reached pathological complete responses or major pathological responses. After a median follow-up of 17.0 months, the 1-year disease-free survival (DFS) and overall survival (OS) rates were 87.2% and 97.4%, respectively. The pathological response showed a significantly positive association with survival benefits (p < 0.001). Patients with human papillomavirus (HPV)-positive oropharyngeal cancer had the best pathological response and survival outcomes. Besides, history of radiation at head and neck region and poor pathological response were found to be independent risk factors of DFS for patients receiving such treatments. Conclusion: Neoadjuvant chemoimmunotherapy of HNSCC showed high rate of pathological response and low recurrence rate, holding promise for becoming the new standard of care for resectable HNSCC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]