Tumor immune microenvironment remodeling and prognosis of patients with esophageal squamous cell carcinoma after neoadjuvant chemotherapy with and without immunotherapy: a retrospective cohort study.

Background: Immunochemotherapy was an emerging neoadjuvant treatment mode that can potentially benefit patients with esophageal carcinoma, but its synergistic mechanism and impact on the tumor immune microenvironment were still unclear. The purpose of this study was to investigate the outcomes of neoadjuvant chemotherapy (nCT) and neoadjuvant immunochemotherapy (nICT) in tumor microenvironment (TME) remodeling among patients with esophageal squamous cell carcinoma (ESCC) and to evaluate the prognostic value of immune-related biomarkers and clinicopathological characteristics. Methods: Patients with locally advanced ESCC who underwent neoadjuvant therapy followed by esophagectomy at the Fourth Hospital of Hebei Medical University between December 2019 and March 2022 were enrolled in this retrospective study. We examined TME features and immune antigen-related biomarkers before and after neoadjuvant therapy. Logistic and Cox regression model were used to evaluate the correlation between these factors and other clinical features and outcomes. Results: A total of 50 eligible participants were analyzed, including 31 males (62%), 25 patients of ≥65 years old, 4/28/18 of upper/middle/lower thoracic cancer, 25/17/8 of poor/moderate/high tumor differentiation, 8/42 of cT1+2/T3+4 stages and 30/20 of cN0/N+ stages. In the entire cohort, the rates of pathological complete response (pCR) and major pathological response (MPR) were 18% and 30%, respectively. pCR rates were 7.1% and 22.2% (χ2=0.699; P=0.40) MPR rates were 7.1% and 38.9% (χ2=4.837; P=0.03) in the nCT and nICT groups, respectively. Compared with the non-pCR patients, the pCR patients had a higher baseline programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) positive expression rate (16.7% vs. 77.8%, χ2=13.089; P<0.001). Following neoadjuvant therapy, the expression rates of PD-L1, CD3+ T cells, and CD8+ T cells in the tumor tissue was higher in the nICT group compared to the nCT group (P<0.05). Deficient expression of mismatch repair (MMR) genes was only observed in one patient (2%). Among patient-related biomarkers, lymphocyte and neutrophil counts decreased after treatment, with no significant changes in the neutrophil-to-lymphocyte ratio or platelet-to-lymphocyte ratio (PLR). Cox regression analysis showed that pretreatment, well-differentiated tumors and positive PD-L1 status were positive predictors of MPR (P<0.05). MPR was an independent predictor of disease-free survival (DFS) (P=0.03). Conclusions: Compared to nCT, nICT could more significantly upregulates PD-L1 TPS, PD-L1 combined positive score (CPS), CD3+ T cells, and CD8+ T cells. Pretreatment tumor differentiation and PD-L1 TPS level could be predictive of MPR. Our findings suggested that the combination of chemotherapy and immunotherapy may be more beneficial for activating anti-tumor immunity in the TME.

Evaluation of oxaliplatin and tigio combination therapy in locally advanced gastric cancer.

BACKGROUND: Locally advanced gastric cancer (LAGC) is a common malignant tumor. In recent years, neoadjuvant chemotherapy has gradually become popular for the treatment of LAGC. AIM: To investigate the efficacy of oxaliplatin combined with a tigio neoadjuvant chemotherapy regimen vs a conventional chemotherapy regimen for LAGC. METHODS: Ninety patients with LAGC were selected and randomly divided into control and study groups with 45 patients in each group, according to the numerical table method. The control group was treated with conventional chemotherapy, and the study group was treated with oxaliplatin combined with tigio-neoadjuvant chemotherapy. The primary outcome measures were the clinical objective response rate (ORR) and surgical resection rate (SRR), whereas the secondary outcome measures were safety and Karnofsky Performance Status score. RESULTS: The ORR in the study group was 80.00%, which was significantly higher than that of the control group (57.78%). In the study group, SRR was 75.56%, which was significantly higher than that of the control group (57.78%). There were 15.56% adverse reactions in the study group and 35.56% in the control group. These differences were statistically significant between the two groups. CONCLUSION: The combination of oxaliplatin and tigio before surgery as neoadjuvant chemotherapy for patients with LAGC can effectively improve the ORR and SRR and is safe.

Compare clinical efficacy and safety of neoadjuvant therapy and neoadjuvant chemoradiotherapy for locally advanced rectal cancer: Meta-analysis.

BACKGROUND: To compare the efficacy and safety of total neoadjuvant therapy (TNT) and neoadjuvant chemoradiotherapy (nCRT) in the treatment of middle and low locally advanced rectal cancer. Our study will systematically collect and integrate studies to evaluate the ability of these two treatments to improve tumor shrinkage rates, surgical resection rates, tumor-free survival, and severe adverse events. AIM: To provide clinicians and patients with more reliable treatment options to optimize treatment outcomes and quality of life for patients with locally advanced rectal cancer by comparing the advantages and disadvantages of the two treatment options. METHODS: A full search of all clinical studies on the effectiveness and safety of TNT and nCRT for treating locally advanced rectal cancer identified in Chinese (CNKI, Wanfang, China Biomedical Literature Database) and English (PubMed, Embase) databases was performed. Two system assessors independently screened the studies according to the inclusion and exclusion criteria. Quality evaluation and data extraction were performed for the included literature. We used RevMan 5.3 software to perform a meta-analysis of the pathologic complete response (pCR) rate, T stage degradation rate, resection 0 (R0) rate, anal grade 3/4 acute toxicity rate, perioperative complications, overall survival (OS), and disease-free survival (DFS) in the TNT and nCRT groups. RESULTS: Finally, 14 studies were included, six of which were randomized controlled studies. A total of 3797 patients were included, including 1865 in the TNT group and 1932 in the nCRT group. The two sets of baseline data were comparable. The results of the meta-analysis showed that the pCR rate [odds ratio (OR) = 1.57, 95% confidence interval (CI): 1.30-1.90, P < 0.00001], T stage degradation rate (OR = 2.16, 95%CI: 1.63-2.57, P < 0.00001), and R0 resection rate (OR = 1.42, 95%CI: 1.09-1.85, P = 0.009) were significantly greater in the nCRT group than in the nCRT group. There was no significant difference in the incidence of grade 3/4 acute toxicity or perioperative complications between the two groups. The 5-year OS [hazard ratio (HR) = 0.84, 95%CI: 0.69-1.02, P = 0.08] and DFS (HR = 0.94, 95%CI: 0.03-1.39, P = 0.74) of the TNT group were similar to those of the nCRT group. CONCLUSION: TNT has greater clinical efficacy and safety than nCRT in the treatment of locally advanced rectal cancer.

Pulmonary function test-related prognostic models in non-small cell lung cancer patients receiving neoadjuvant chemoimmunotherapy.

Background: This study aimed to establish a comprehensive clinical prognostic risk model based on pulmonary function tests. This model was intended to guide the evaluation and predictive management of patients with resectable stage I-III non-small cell lung cancer (NSCLC) receiving neoadjuvant chemoimmunotherapy. Methods: Clinical pathological characteristics and prognostic survival data for 175 patients were collected. Univariate and multivariate Cox regression analyses, and least absolute shrinkage and selection operator (LASSO) regression analysis were employed to identify variables and construct corresponding models. These variables were integrated to develop a ridge regression model. The models' discrimination and calibration were evaluated, and the optimal model was chosen following internal validation. Comparative analyses between the risk scores or groups of the optimal model and clinical factors were conducted to explore the potential clinical application value. Results: Univariate regression analysis identified smoking, complete pathologic response (CPR), and major pathologic response (MPR) as protective factors. Conversely, T staging, D-dimer/white blood cell ratio (DWBCR), D-dimer/fibrinogen ratio (DFR), and D-dimer/minute ventilation volume actual ratio (DMVAR) emerged as risk factors. Evaluation of the models confirmed their capability to accurately predict patient prognosis, exhibiting ideal discrimination and calibration, with the ridge regression model being optimal. Survival analysis demonstrated that the disease-free survival (DFS) in the high-risk group (HRG) was significantly shorter than in the low-risk group (LRG) (P=2.57×10-13). The time-dependent receiver operating characteristic (ROC) curve indicated that the area under the curve (AUC) values at 1 year, 2 years, and 3 years were 0.74, 0.81, and 0.79, respectively. Clinical correlation analysis revealed that men with lung squamous cell carcinoma or comorbid chronic obstructive pulmonary disease (COPD) were predominantly in the LRG, suggesting a better prognosis and potentially identifying a beneficiary population for this treatment combination. Conclusion: The prognostic model developed in this study effectively predicts the prognosis of patients with NSCLC receiving neoadjuvant chemoimmunotherapy. It offers valuable predictive insights for clinicians, aiding in developing treatment plans and monitoring disease progression.

Effectiveness and safety of neoadjuvant therapy in triple-negative breast cancer in a real-world population. / [Artículo traducido] Efectividad y seguridad del tratamiento neoadyuvante del cáncer de mama triple negativo en la vida real.

OBJECTIVE: Triple-negative breast cancer is a subtype of aggressive breast cancer. Our aim is to evaluate the effectiveness and safety of neoadjuvant treatment in early-stage triple-negative breast cancer and to identify predictors of pathological complete response. METHODS: This is a single-center, retrospective study involving 79 patients with triple-negative breast cancer who initiated neoadjuvant treatment between January 2017 and October 2022. Descriptive analyses were performed as appropriate. Statistical analysis utilized bivariate logistic regression to explore the presence of factors related to pathological complete response, and the Kaplan-Meier method was employed for survival analysis. RESULTS: In the overall population, 27 patients (n = 78; 34.6%) achieved pathological complete response in the breast and axillary lymph nodes, and 31 (n = 73; 42.5%) achieved a grade 5 pathological complete response in the breast, according to the Miller and Payne classification. The addition of platinum to standard therapy improved both breast and axillary lymph node pathological complete response rates. Age less than 40 years was identified as a predictor of pathological complete response in our study population through bivariate analysis, while Ki67 levels lower than 70% were associated with a lower pathological complete response rate. Adverse events were reported in 72 patients (91.1%), with grade 3-5 adverse events observed in 33 (41.8%). There was a particularly notable increase in gastrointestinal and hematological adverse events when platinum was added. CONCLUSIONS: In this population, we observed moderate rates of pathological complete response with acceptable chemotherapy tolerance. Platinum-based chemotherapy appears to enhance the likelihood of achieving pathological complete response, albeit with a less favorable safety profile. Therefore, evaluating the benefit-risk balance is crucial when selecting the optimal chemotherapy regimen for individual patients.

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.

Pancreatoduodenectomy with colon-last approach for advanced pancreatic head cancer.

PURPOSE: Margin-negative surgery is very important in surgical oncology. Considering margin-negative pancreatectomy is known to be essential for cure of the pancreatic cancer, pancreatoduodenectomy with combined venous vascular or arterial resection can be a potential option for margin-negative resection, especially, in era of neoadjuvant treatment with potent systemic chemotherapy. To the contrary, special attention was not paid on combined colonic resection during PD. In this article, safe surgical technique for PD with combined colonic resection is introduced, under the name of PD with "colon-last" approach. METHODS: At Severance Hospital (Yonsei University College of Medicine, Seoul, Republic of Korea), between 2014 and 2021, a total of six patients underwent PD with "colon-last" approach. The surgical technique and surgical outcome are reviewed. RESULTS: All patients recovered without major complications (Clavien-Dindo classification grade ≥ III) after surgery, and most of them recovered after conservative treatment with postoperative pancreatic fistula biochemical leak. None of the patients were readmitted. Only the first and second cases represent cancer-related mortality, and the other patients are still alive and are being followed up. CONCLUSION: It is hoped that the present technique, PD with colon-last approach, could be helpful enhance the procedural safety in treating advanced cancer requiring PD with combined colon resection. However, its technical safety and oncologic role should be validated by many pancreatic surgeons' collaborative studies in the near future.

Risk of hepatic steatosis with the preoperative treatment of pancreatic cancer and the short-term postoperative outcomes.

PURPOSE: We investigated whether the preoperative treatment of patients with pancreatic cancer is a risk factor for hepatic steatosis (HS), and whether preoperative HS affects the short-term postoperative outcomes. METHODS: Patients who underwent radical surgery for pancreatic cancer between 2010 and 2023 were enrolled. The patients' medical records were reviewed. Albumin and carbohydrate antigen 19-9 were measured before and after chemotherapy in the patients who received preoperative chemotherapy. A logistic regression univariate analysis was performed to analyze the factors associated with new-onset HS. RESULTS: A total of 230 patients who underwent surgery were included. HS was observed on the date of surgery in 11 (10%) and two (2%) patients with and without preoperative chemotherapy, respectively. Female sex, initially borderline resectable or unresectable disease, history of cholangitis, presence of PEI, long-term (≥ 3 months) biliary drainage, preoperative chemotherapy, and serum albumin ≥ 3.9 mg/dl before chemotherapy were identified as risk factors for HS. The incidence of postoperative morbidity did not differ between the patients with and without preoperative steatosis. CONCLUSIONS: Preoperative chemotherapy, a history of cholangitis, the presence of PEI, and ≥ 3 months' duration of biliary drainage were risk factors for the development of HS before surgery for pancreatic cancer. However, preoperative HS did not affect the short-term postoperative outcomes.

Utilization of neoadjuvant chemotherapy for muscle-invasive bladder cancer in elderly patients: a retrospective cohort study.

Neoadjuvant chemotherapy (NAC) improves overall survival in muscle-invasive bladder cancer (MIBC). Older patients often do not receive NAC due to its potential toxicities. We examined treatment patterns of elderly MIBC patients as well as impact of NAC on survival in this population. The National Cancer Database was queried from 2006 to 2019 for stage T2-T4a MIBC patients ≥ 80 years old. Treatment exposures (extirpative surgery; chemotherapy; radiation) were ascertained. Kaplan-Meier survival curves were generated based on treatment modalities (no treatment; radiation only; chemotherapy only; chemoradiation; surgery only; NAC with surgery). Multivariable Cox proportional hazards regression assessed associations with overall survival (OS). The cohort included 16,391 patients (mean age 86 years); 51% received treatment. MIBC treatment was less common with advancing age; patients receiving NAC then surgery were younger and had lower comorbidity scores. From 2006 to 2019, more patients received chemoradiation, while rates of NAC rose modestly. Median OS for the NAC with surgery group was 48 months versus 9 months for the no treatment group. Log-rank tests showed significantly improved survival in the NAC with surgery group compared to the surgery only group, while Cox proportional hazards regression analysis showed highest survival benefit in the NAC with surgery group. Only half of elderly MIBC patients received treatment, with fewer undergoing curative intent. NAC with surgery was associated with the greatest survival benefit. While our findings should be taken in the context of potential selection bias and patient preferences, they support NAC as part of shared-decision making regardless of age.

Impact of Margin Status on Local Recurrence in Patients with Breast Cancer Undergoing Breast-Conserving Surgery After Neoadjuvant Chemotherapy: A Retrospective Multi-Institutional Cohort Study.

BACKGROUND: Questions have been raised as to an increased risk of local recurrence with breast-conserving surgery (BCS) post NAC highlighting the uncertainty around optimal margin width in this patient population. We examined the association between margin status and local recurrence-free survival (LRFS) in patients who underwent BCS following NAC. METHODS: We performed a retrospective cohort study of adult female patients with stage I-III breast cancer who underwent NAC followed by BCS between 2012 and 2021 at two cancer centers. Margins were categorized as "close" if they were < 1 mm. RESULTS: The full cohort included 544 patients with a median age of 53 years (interquartile range [IQR] 44-64). Pathologic complete response (pCR) was achieved in 41.2% of the overall cohort (n = 224). Of the 320 with residual disease, 29.4% (n = 94) had at least one close margin, and 10.9% (n = 35) had ≥2 close margins. Median follow-up was 55 months (IQR 32-83); 4.8% had an ipsilateral breast recurrence (n = 26). Patients with pCR had a higher 5-year LRFS than those with residual disease (98.0% vs. 91.6%, p = 0.02). There was no difference in 5-year LRFS between the margin categories (clear vs. 1 close margin vs. ≥2 close margins) in those with residual disease (92.2% vs. 88.9% vs. 92.9%) (p = 0.78). CONCLUSIONS: In patients undergoing BCS post-NAC, those who achieved pCR had a significantly higher LRFS compared with those with residual disease at the time of surgery, but LRFS was not associated with margin width nor the number of close margins.

Promoter profiles in plasma CfDNA exhibits a potential utility of predicting the efficacy of neoadjuvant chemotherapy in breast cancer patients.

BACKGROUND: Gene expression profiles in breast tissue biopsies contain information related to chemotherapy efficacy. The promoter profiles in cell-free DNA (cfDNA) carrying gene expression information of the original tissues may be used to predict the response to neoadjuvant chemotherapy in breast cancer as a non-invasive biomarker. In this study, the feasibility of the promoter profiles in plasma cfDNA was evaluated as a novel clinical model for noninvasively predicting the efficacy of neoadjuvant chemotherapy in breast cancer. METHOD: First of all, global chromatin (5 Mb windows), sub-compartments and promoter profiles in plasma cfDNA samples from 94 patients with breast cancer before neoadjuvant chemotherapy (pCR = 31 vs. non-pCR = 63) were analyzed, and then classifiers were developed for predicting the efficacy of neoadjuvant chemotherapy in breast cancer. Further, the promoter profile changes in sequential cfDNA samples from 30 patients (pCR = 8 vs. non-pCR = 22) during neoadjuvant chemotherapy were analyzed to explore the potential benefits of cfDNA promoter profile changes as a novel potential biomarker for predicting the treatment efficacy. RESULTS: The results showed significantly distinct promoter profile in plasma cfDNA of pCR patients compared with non-pCR patients before neoadjuvant chemotherapy. The classifier based on promoter profiles in a Random Forest model produced the largest area under the curve of 0.980 (95% CI: 0.978-0.983). After neoadjuvant chemotherapy, 332 genes with significantly differential promoter profile changes in sequential cfDNA samples of pCR patients was observed, compared with non-pCR patients, and their functions were closely related to treatment response. CONCLUSION: These results suggest that promoter profiles in plasma cfDNA may be a powerful, non-invasive tool for predicting the efficacy of neoadjuvant chemotherapy breast cancer patients before treatment, and the on-treatment cfDNA promoter profiles have potential benefits for predicting the treatment efficacy.

Clinical implications of serum miR-34a in breast cancer and its predictive value for the efficacy of neoadjuvant chemotherapy.

OBJECTIVES: This study aims to explore the implications of serum miR-34a in breast cancer (BC) and its predictive value for the efficacy of neoadjuvant chemotherapy (NACT). METHODS: A retrospective analysis was performed on 102 female BC patients (research group) admitted to The Second Affiliated Hospital of Anhui Medical University between January 2016 to March 2018 and 102 concurrent female health controls who underwent physical examinations (control group). Serum samples from both groups were subjected to quantitative reverse transcription polymerase chain reaction to measure miR-34a expression. The correlation of miR-34a with BC patients' clinical parameters was analyzed, and the implications of miR-34a for diagnosing BC and predicting NACT efficacy were assessed by receiver operating characteristic curves. Logistic regression analysis was employed to determine whether miR-34a independently influenced treatment effectiveness and patient outcomes. RESULTS: The data showed significantly lower miR-34a levels in the research group than in the control group (P<0.05). The area under the curve (AUC) of miR-34a for differentiating BC was 0.888. In BC patients, miR-34a was strongly correlated with tumor staging and differentiation degree. Following NACT, BC patients showed an evident rise in miR-34a expression, with higher levels in patients with effective treatment compared to those with treatment failure (P<0.05). The AUC values of serum miR-34a in predicting the efficacy of neoadjuvant chemotherapy from FD to SD and from SD to TD were 0.880 and 0.861, respectively (P<0.001). Furthermore, patients with favorable prognosis exhibited markedly higher serum miR-34a expression than those with poor prognosis (P<0.05). The AUC of miR-34a expression for predicting adverse prognosis was 0.825. Decreased miR-34a was identified as an independent risk factor for treatment failure and poor prognosis. CONCLUSIONS: Taken together, serum miR-34a is downregulated in BC and can predict the clinical progression of BC patients and the therapeutic efficacy of NACT.

Comparison of radiotherapy versus surgical resection following neoadjuvant chemoimmunotherapy in potentially resectable stage III non-small-cell lung cancer: A propensity score matching analysis.

BACKGROUND: Neoadjuvant chemoimmunotherapy followed by surgery is recommended for resectable non-small-cell lung cancer (NSCLC). However, a considerable proportion of patients do not undergo surgery and opt for alternative treatments such as radiotherapy. The efficacy of radiotherapy in this context remains unclear. METHODS: This retrospective study analyzed data from patients with stage III NSCLC who received neoadjuvant chemoimmunotherapy followed by either surgery or radiotherapy. Propensity score matching (PSM) was used to balance the heterogeneity between the groups. Efficacy outcomes, safety profiles, and disease recurrence patterns were assessed. RESULTS: In total, 175 patients were included; 50 underwent radiotherapy, and 125 underwent surgery. Prior to matching, radiotherapy was inferior to surgery in terms of progression-free survival (PFS; Hazard ratio [HR], 2.23; P = 0.008). Following a 1:1 PSM adjustment, each group consisted of 40 patients. The median PFS was 30.8 months in the radiotherapy group and not reached in the surgery group (HR, 1.46; P = 0.390). The 12- and 24-month PFS rates were 90.4 % and 69.0 % for the radiotherapy group compared to 94.1 % and 73.9 % for the surgery group, respectively. Subgroup analyses after PSM showed that patients with stage IIIA disease tend to benefit more from surgery than those with stage IIIB disease (HR, 3.00; P = 0.074). Grade 3-4 treatment-related adverse events (TRAEs) occurred in 62.5 % of patients in the radiotherapy group and 55.0 % in the surgery group, with no grade 5 TRAEs reported. The incidence of grade 3-4 treatment-related pneumonitis or pneumonia was 7.5 % and 2.5 % in the radiotherapy and surgery groups, respectively. CONCLUSION: Radiotherapy may be a viable alternative to surgery in patients with resectable NSCLC who do not undergo surgical resection after initial neoadjuvant chemoimmunotherapy, offering comparable efficacy and a manageable safety profile. Larger prospective studies are needed to validate these findings and optimize the treatment strategies for this patient population.

Multiparametric MRI-based radiomic models for early prediction of response to neoadjuvant systemic therapy in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is often treated with neoadjuvant systemic therapy (NAST). We investigated if radiomic models based on multiparametric Magnetic Resonance Imaging (MRI) obtained early during NAST predict pathologic complete response (pCR). We included 163 patients with stage I-III TNBC with multiparametric MRI at baseline and after 2 (C2) and 4 cycles of NAST. Seventy-eight patients (48%) had pCR, and 85 (52%) had non-pCR. Thirty-six multivariate models combining radiomic features from dynamic contrast-enhanced MRI and diffusion-weighted imaging had an area under the receiver operating characteristics curve (AUC) > 0.7. The top-performing model combined 35 radiomic features of relative difference between C2 and baseline; had an AUC = 0.905 in the training and AUC = 0.802 in the testing set. There was high inter-reader agreement and very similar AUC values of the pCR prediction models for the 2 readers. Our data supports multiparametric MRI-based radiomic models for early prediction of NAST response in TNBC.

A Single-Arm Phase II Clinical Trial of Fulvestrant Combined with Neoadjuvant Chemotherapy of ER+/HER2- Locally Advanced Breast Cancer: Integrated Analysis of 18F-FES PET-CT and Metabolites with Treatment Response.

Purpose: This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to NCT in patients with ER+/HER2- locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 18F-FES PET-CT and metabolites with efficacy. Materials and Methods: Fulvestrant and EC-T regimen were given to ER+/HER2- LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for LC-MS analysis. The primary endpoint was ORR. Secondary endpoints included tpCR and safety. Results: Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥3 TEAEs was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p<0.05). The SUVmax, SUVmean, TL-ER of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p<0.05). Moreover, these parameters were significantly correlated with MP grade and the change in ER expression before and after treatment (p<0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. Conclusion: This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

Risk Stratification Tools to Aid Decisions on Adjuvant Chemotherapy Usage in Resected Soft Tissue Sarcomas: A Ten-Year Review of an Irish Sarcoma Center Experience.

Background: Soft tissue sarcoma (STS) is comprised of approximately 80 subtypes, with an incidence of 4 - 5 per 100,000 annually in Europe. The National Comprehensive Cancer Network (NCCN) guidelines recommend consideration of neoadjuvant/adjuvant chemotherapy in tumors at high risk of recurrence based on the American Joint Committee on Cancer (AJCC) staging. Alternatively, the Sarculator is a risk prediction tool that has identified a threshold of risk, above which chemotherapy may provide an overall survival (OS) benefit. Using this nomogram, patients with a 10-year predicted OS < 60% are classified as high risk and should be considered for chemotherapy. The aim of this study was to assess the prognostic accuracy of these two risk prediction methods in an Irish population. Methods: All newly diagnosed patients with resected STS discussed in the STS tumor board in Cork University Hospital between January 2012 and December 2021 were identified. Clinicopathological data were collected. Risk assessment using AJCC and Sarculator nomogram was performed on all patients with an extremity/trunk sarcoma. The OS was calculated including Kaplan-Meier method for time to event analysis. Results: In total, 200 STS patients were reviewed, of whom 134 had truncal or extremity tumors. Sarculator score was calculated for 60 of these (well differentiated liposarcomas, desmoid tumors and dermatofibrosarcoma protuberans were excluded). Using the Sarculator nomogram to calculate 10-year predicted OS, 19 patients were categorized as high risk and 41 were categorized as low risk. Using AJCC staging, 25 patients were categorized as high risk and 35 as low risk. The 5-year OS rate in the Sarculator high-risk group was 60.2%, compared with 87.1% in the low-risk group (P = 0.009). The 5-year OS rate in the AJCC high-risk group was 67.6%, compared with 86.3% in the low-risk group (P = 0.083). Conclusions: Our cohort is representative of the broad histological subtypes expected. In our population, Sarculator score results correlate with international outcomes and higher scores were associated with increased mortality. The Sarculator was more predictive of clinical outcome than AJCC staging, and its use would lower the proportion of patients being considered for adjuvant chemotherapy thereby sparing toxicity, which is important in the setting of uncertain clinical benefit.

Evaluating Postoperative Prognosis: A Single Surgeon's Experience With Total Mesorectal Excision in Middle and Lower Rectal Cancer Cases in Iraq.

INTRODUCTION: Surgical intervention for rectal cancer is widely recognized for its potential to significantly impact quality of life, chiefly due to the high probability of permanent colostomy and the associated postoperative complications. OBJECTIVE: This study aimed to evaluate the short-term outcomes and morbidity associated with total mesorectal excision for middle and lower rectal cancer within an Iraqi cohort, in a prospective setting. METHODS: This study prospectively collected and analyzed data from 89 patients who underwent a standardized radical rectal resection, with a follow-up period extending to one month post-surgery. RESULTS: The mean age of patients was 54.4 ± 12.9 years, with a gender distribution of 46 males and 43 females. A total of 33 patients presented with preoperative comorbidities, which heightened the risk of adverse short-term outcomes by a factor of 7.51. The most prevalent comorbidities were hypertension and diabetes mellitus, affecting 22 and 20 patients, respectively. Patients aged 60 years and above were at a 3.97 times greater risk of developing complications. The overall complication rate was 21.35%, with wound infections (9.0%) and cardiovascular events (3.4%) being the most common. Mortality during the follow-up was 1.1%. CONCLUSION: The findings indicate that increased age and the presence of comorbidities are significant risk factors for morbidity and mortality post-surgery. Neoadjuvant chemoradiotherapy or radiotherapy was shown to reduce morbidity and mortality rates while improving survival. The morbidity and mortality rates observed in this study concur with existing literature.

Exploring potential predictive biomarkers through historical perspectives on the evolution of systemic therapies into the emergence of neoadjuvant therapy for the treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), a type of liver cancer, ranks as the sixth most prevalent cancer globally and represents the third leading cause of cancer-related deaths. Approximately half of HCC patients miss the opportunity for curative treatment and are then limited to undergoing systemic therapies. Currently, systemic therapy has entered the era of immunotherapy, particularly with the advent of immune-checkpoint inhibitors (ICIs), which have significantly enhanced outcomes for patients with advanced HCC. Neoadjuvant treatment for HCC has become a possibility-findings from the IMbrave 050 trial indicated that ICIs offer the benefit of recurrence-free survival for high-risk HCC patients post-resection or local ablation. However, only a small fraction of individuals benefit from systemic therapy. Consequently, there is an urgent need to identify predictive biomarkers for treatment response and outcome assessment. This study reviewed the historical progression of systemic therapy for HCC, highlighting notable therapeutic advancements. This study examined the development of systemic therapies involving conventional drugs and clinical trials utilized in HCC treatment, as well as potential predictive biomarkers for advanced and/or locally advanced HCC. Various studies have revealed potential biomarkers in the context of HCC treatment. These include the association of dendritic cells (DCs) with a favorable response to neoadjuvant therapy, the presence of enriched T effector cells and tertiary lymphoid structures, the identification of CD138+ plasma cells, and distinct spatial arrangements of B cells in close proximity to T cells among responders with locally advanced HCC receiving neoadjuvant cabozantinib and nivolumab treatment. Furthermore, pathological response has been associated with intratumoral cellular triads consisting of progenitor CD8+ T cells and CXCL13+ CD4+ T helper cells surrounding mature DCs in patients receiving neoadjuvant cemiplimab for resectable HCC. Despite no widely recognized predictive biomarkers for HCC individualized treatment, we believe neoadjuvant trials hold the most promise in identifying and validating them. This is because they can collect multiple samples from resectable HCC patients across stages, especially with multi-omics, bridging preclinical and clinical gaps.

Successful management of locally advanced cervical cancer via total pelvic exenteration following neoadjuvant chemotherapy.

Stage IVA cervical cancer is a tumor that invades the mucosa of the bladder or rectum without distant metastasis and is difficult to treat, and concurrent chemoradiotherapy is recommended. Although radical surgery following neoadjuvant chemotherapy is a treatment option for stage IVA cervical cancer, the evidence is limited. A 51-year-old woman with bulky cervical cancer and rectal invasion was referred to our hospital. Paclitaxel and cisplatin were administered as neoadjuvant chemotherapies. After two cycles of chemotherapy, the tumor size decreased markedly. Total pelvic exenteration was performed, and a complete resection was achieved. Four cycles of paclitaxel and cisplatin were administered postoperatively. Thirty-three months after the completion of adjuvant chemotherapy, the patient was alive and free of disease. Radical surgery after neoadjuvant chemotherapy may be a treatment option for stage IVA cervical cancer with bulky tumors.