Pathological Response Research Articles

Association between mammographic breast density and outcome in patients with unilateral invasive breast cancer receiving neoadjuvant chemotherapy.

To analyze the relationship between mammographic breast density and tumor response and outcome at follow-up, in terms of overall survival (OS) and disease-free survival (DFS), in patients with unilateral invasive breast cancer receiving neoadjuvant chemotherapy (NACT). A total of 228 women (mean age, 47.6years ± 10 [SD]; range: 24-74years) with invasive breast cancer who underwent NACT were included in this observational retrospective study. Clinical, radiological and histopatological data were retrieved. Categorization of breast density was performed by two radiologists in consensus on mammography acquired at the time of diagnosis according to BI-RADS categories. Association between density categories and tumor response was analyzed in the overall population and in subgroups defined by menopausal status, tumor phenotype and stage at diagnosis. Kaplan-Meier (KM) curves were used to estimate the OS and DFS probabilities. Subgroup analyses based on menopausal status and tumor phenotype were performed. A total of 30 patients (13.2%) achieved pathological complete response (pCR). No association between density categories and pCR was found (P = 0.973), even at subgroups analysis. The median follow-up time was 92months. Patients with dense breast showed the longest DFS (P = 0.0094), results confirmed in premenopausal patients (P = 0.0024) and in triple negative breast cancers (P = 0.0292). Density category did not show a statistically significant association with OS. Breast cancer patients receiving NACT with extremely dense breasts showed better DFS. No evidence of breast density as a predictive marker for complete pathological response or as a prognostic factor in terms of OS was found.

Abstract 4133460: VCAM1 contributes to pathogenesis during influenza-induced exacerbation of atherosclerosis.

Background and hypothesis: Influenza is a significant public health and economic threat around the world. Although pneumonia is the most common complication associated with influenza, there are several clinical reports demonstrating increased risk for cardiovascular disease. Influenza infection induces interferons, proinflammatory cytokines and chemokines, and recruits’ macrophages and neutrophils to control the virus. However, an excessive influx of innate immune cells and dysregulated production of inflammatory mediators results in pathological responses during influenza infection. Studies have shown that influenza infection correlates with increased incidence of myocardial infarction. Atherosclerosis is the most known cause of ischemic heart diseases and stroke. Vascular cell adhesion molecule-1 (VCAM1) has been shown to promote adhesion of monocytes and promotes atherosclerosis. In this study, we hypothesize that VCAM1 plays a role in exacerbation of atherosclerosis during influenza infection. Methods: High-Fat diet (HFD)-fed Apoe -/- mice were infected with influenza A/PR/8/34 (H1N1) and weight loss, survival rate, and gene expression of vascular endothelial adhesion molecules, inflammatory cytokines and chemokines were measured. HFD-fed Apoe -/- mice were infected with influenza, and treated with anti-VCAM1 antibody, and weight loss and cellular responses were measured. Results and conclusions: Increased weight loss and decreased survival of mice were observed in response to influenza infection in HFD-induced atherosclerosis in Apoe -/- mice. Further, the expression of VCAM1, and the levels of IL-6, CCL2, CCL3, CCL5 were significantly increased in aorta in Apoe -/- mice when compared to PBS-treated controls. Increased survival, decreased weight loss, decreased lesion area, decreased frequency of CD11b + F4/80 + Ly6C + , CD4 + RORgt + cells and increased frequency of CD4 + FoxP3 + Treg cells were observed in aorta in response to antibody mediated VCAM1 neutralization. These results suggest that VCAM1 plays a pathological role in influenza-induced exacerbation of atherosclerosis.

Evaluation of Volumetric Magnetic Resonance Imaging in Determining the Indication for Total Neoadjuvant Therapy in Rectal Cancer.

This study aims to evaluate the relationship between volumetric measurements of residual tumor via magnetic resonance imaging (MRI) and pathologic complete response (pCR) in rectal cancer patients undergoing neoadjuvant chemoradiotherapy (nCRT). Patients with locally advanced rectal cancer who had pelvic MRI for clinical staging and completed nCRT followed by radical resection were included. Two experienced radiologists measured tumor volume on MRI obtained before and after nCRT. We compared the pre- and post-CRT tumor volume and measured tumor volume reduction rates. The median value of tumor volume reduction rate in all patients was 64.7% (min-max - 81.1-98.1%). When the relationship between tumor volume and tumor regression grade (TRG) after nCRT was assessed, it was found that 18 of 21 (86%) patients with a good response (TRG 1) had a post-CRT tumor volume of ≤ 8 cm3 (p = 0.001). While 9 of 10 patients with pCR after nCRT had a tumor volume of ≤ 8 cm3, one patient had pCR despite having a tumor volume greater than 8 cm3 (p = 0.015). The correlation between post-nCRT residual tumor volume and pCR underscores the potential of volumetric MRI as a predictive tool in tailoring rectal cancer treatment. For patients with residual tumor volumes greater than 8 cm3, extending neoadjuvant chemotherapy as part of TNT may enhance the likelihood of achieving pCR. This approach advocates for a more personalized treatment strategy, potentially optimizing outcomes for rectal cancer patients.

Target-Engineered Liposomes Decorated with Nanozymes Alleviate Liver Fibrosis by Remodeling the Liver Microenvironment.

Liver fibrosis is a pathological repair response that occurs after sustained liver damage, and prompt intervention is necessary to prevent liver fibrosis from developing into a potentially life-threatening condition. In long-term liver injury, damaged hepatocytes produce excessive amounts of reactive oxygen species (ROS), which activate hepatic stellate cells (HSCs). This activation leads to excessive accumulation of extracellular matrix proteins in liver tissue. Additionally, liver macrophages contribute to the inflammatory microenvironment in the hepatic fibrotic process, exacerbating liver fibrosis through ROS production and the secretion of pro-inflammatory factors. To address the dysregulation of the hepatic microenvironment associated with liver fibrosis, we developed cerium oxide nanozymes using hyaluronic acid (HA) as a template and decorated them on the surface of liposomes loaded with oleanolic acid (OA). We named this prepared and obtained target-engineered liposome HCOL. The inherent superoxide dismutase (SOD) and catalase (CAT) activities of HCOL enabled it to effectively scavenge ROS in HSCs and alleviate the hypoxic conditions characteristic of fibrotic livers. Furthermore, HCOL reduced the concentrations of ROS in macrophages, promoting a shift in macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. This transition increased the production of the anti-inflammatory cytokine interleukin 10 (IL-10), which contributed to the mitigation of the inflammatory microenvironment. Consequently, this therapeutic approach proves effective in decelerating the advancement of liver fibrosis.

Experts' Cognition-Driven Ensemble Deep Learning for External Validation of Predicting Pathological Complete Response to Neoadjuvant Chemotherapy from Histological Images in Breast Cancer

In breast cancer, neoadjuvant chemotherapy (NAC) provides a standard treatment option for patients who have locally advanced cancer and some large operable tumors. A patient will have better prognosis when he has achieved a pathological complete response (pCR) with the treatment of NAC. There has been a trend to directly predict pCR to NAC from histological images based on deep learning (DL). However, the DL-based predictive models numerically have better performances in internal validation than in external validation. In this paper, we aim to alleviate this situation with an intrinsic approach. We propose an experts’ cognition-driven ensemble deep learning (ECDEDL) approach. Taking the cognition of both pathology and artificial intelligence experts into consideration to improve the generalization of the predictive model to the external validation, ECDEDL can intrinsically approximate the working paradigm of a human being which will refer to his various working experiences to make decisions. ECDEDL was validated with 695 WSIs collected from the same center as the primary dataset to develop the predictive model and perform the internal validation, and was also validated with 340 WSIs collected from other three centers as the external dataset to perform the external validation. In external validation, ECDEDL improves the AUCs of pCR prediction from 61.52(59.80-63.26) to 67.75(66.74-68.80) and the Accuracies of pCR prediction from 56.09(49.39-62.79) to 71.01(69.44-72.58). ECDEDL was quite effective for external validation of predicting pCR to NAC from histological images in breast cancer, numerically approximating the internal validation.

Ki-67 With MRI in Predicting the Complete Pathological Response Post-neoadjuvant Chemotherapy.

Neoadjuvant chemotherapy (NAC) is increasingly used for high-risk breast cancer to achieve pathologic complete response (pCR), an indicator of event-free survival and favorable survival outcomes. Integrating MRI and Ki-67 biomarker analysis into predictive models offers a promising approach to optimize NAC response assessment and guide personalized treatment strategies. This study evaluates the validity of combined MRI and Ki-67 metrics for predicting pCR. We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, including studies on NAC-treated breast cancer patients assessed by MRI and Ki-67. The predictive models were evaluated based on key parameters, including MRI-based tumor size reduction and Ki-67 levels, with outcomes measured by area under the receiver operating characteristic curve (AUC) and calibration metrics. Findings across ten studies consistently show that high Ki-67 levels and significant tumor size reduction on MRI are predictive of pCR, achieving AUCs near 0.90. The analysis highlighted that models integrating MRI with Ki-67 metrics outperformed single-modality approaches, showing enhanced predictive accuracy and calibration. However, high heterogeneity (I² = 77%) was noted, suggesting variability in imaging and Ki-67 assessment protocols across studies. Thisstudy underscores the combined utility of MRI and Ki-67 for the non-invasive prediction of pCR, offering both structural and biological insights into tumor responsiveness. The results align with prior research, affirming the role of Radiomic-clinicopathological models in providing a more comprehensive assessment compared to individual markers. Further refinement of imaging and biomarker protocols could improve model reproducibility and applicability. Our findings highlight the robust predictive accuracy of MRI-Ki-67 integrated models for assessing pCR, marking a significant step toward personalized cancer care. Future studies should focus on refining these models with additional biomarkers and standardized protocols, facilitating their integration into routine clinical oncology to enhance treatment decision-making and patient outcomes.

Predicting ipsilateral supraclavicular lymph node pathological complete response: nomogram based on the inflammatory markers

BackgroundThe prediction of ISLN pCR after neoadjuvant chemotherapy (NAC) based on inflammatory markers and its prognostic value have rarely been investigated.MethodsPatients diagnosed with ISLN-involved breast cancer who received NAC in West China Hospital between September 2009 and December 2020 were enrolled in the derivation cohort for model construction and survival analysis, and patients with the same criteria between January 2021 and July 2024 were involved in validation cohort for external validation. After randomly dividing patients into training and testing groups at 7:3 ratio, a nomogram predicting ISLN pCR was constructed based on logistic regression in training group. Internal validation was performed in the testing group and external validation was performed in the independent validation cohort. The ROC curves were applied to validate the accuracy of the model. Survival analysis was performed using Kaplan−Meier plots.ResultsA total of 120 eligible patients were involved in the derivation cohort to establish the nomogram (84 patients in training group and 36 patients in testing group), and 45 patients were involved in the independent validation cohort for external validation of the nomogram. Pretreatment NLR and hormone receptor (HR) status, as well as preoperative SII, CEA, CA15-3 and anti-HER2 therapy were included in the nomogram predicting ISLN pCR. The AUC were 0.906 (95% CI 0.837-0.975, P<0.001), 0.888 (95% CI 0.751-1.000, P<0.001) and 0.828 (95% CI 0.703-0.953, P< 0.001) in training, testing groups and the validation cohort respectively. ISLN pCR was significantly associated with better prognosis (all P<0.05).ConclusionInflammatory factors combined with tumor makers, hormone receptor status and anti-HER2 therapy could predict ISLN pCR effectively, which was significantly associated with improved survival outcomes.

Prediction of tumor response to neoadjuvant chemotherapy in high-grade osteosarcoma using clustering-based analysis of magnetic resonance imaging: an exploratory study.

To evaluate the ability of magnetic resonance imaging (MRI)-based clustering analysis to predict the pathological response to neoadjuvant chemotherapy (NACT) in patients with primary high-grade osteosarcoma. Twenty-two patients were included in this retrospective study. All patients underwent MRIs before and after NACT. The entire tumor volume was manually delineated on post-contrast T1-weighted images and subsegmented into three clusters using the K-means algorithm. Histogram-based parameters were calculated for each lesion. The response to NACT was obtained from the histopathological assessment of the tumor necrosis rate following resection. The Mann-Whitney test was used to compare poor and fair-to-good responders. The receiver operating characteristic curve was used to evaluate the diagnostic performance of the optimal parameters. At baseline, poor responders showed a significantly larger volume of cluster1 (Vol1) than fair-to-good responders (p = 0.038). After NACT, they exhibited a lower 10th percentile (P10) and kurtosis (p = 0.038 and 0.002, respectively). Vol1 at baseline and P10 after NACT had an AUC of 77% (95% CI 56-98%). The kurtosis after NACT had the best discriminative power, with an AUC of 89.7% (95% CI 75-100%). The MRI-based histogram and clustering analysis provided a good ability to differentiate between poor and fair-to-good responders before and after NACT. Further investigations using larger datasets are required to corroborate our findings.

APOE from astrocytes restores Alzheimer's Aβ-pathology and DAM-like responses in APOE deficient microglia.

The major genetic risk factor for Alzheimer's disease (AD), APOE4, accelerates beta-amyloid (Aβ) plaque formation, but whether this is caused by APOE expressed in microglia or astrocytes is debated. We express here the human APOE isoforms in astrocytes in an Apoe-deficient AD mouse model. This is not only sufficient to restore the amyloid plaque pathology but also induces the characteristic transcriptional pathological responses in Apoe-deficient microglia surrounding the plaques. We find that both APOE4 and the protective APOE2 from astrocytes increase fibrillar plaque deposition, but differentially affect soluble Aβ aggregates. Microglia and astrocytes show specific alterations in function of APOE genotype expressed in astrocytes. Our experiments indicate a central role of the astrocytes in APOE mediated amyloid plaque pathology and in the induction of associated microglia responses.

Predictive and Prognostic Value of Inflammatory and Nutritional Indexes in Patients with Breast Cancer Receiving Neoadjuvant Chemotherapy

Background and Objectives: Neoadjuvant chemotherapy (NAC) improves survival by increasing pathologic complete response (pCR). Blood-based indexes have been studied in breast cancer for predicting pCR and prognosis, but the results are conflicting. We aimed to assess the impact of inflammatory and nutritional indexes on pCR and survival. Materials and Methods: We retrospectively analyzed 304 patients. Pre-NAC laboratory data were used to calculate their neutrophil-to-lymphocyte ratios (NLR), pan-immune inflammation values (PIV), lactate dehydrogenase–albumin ratios (LAR), and prognostic nutritional indexes. The optimal cut-off values were determined through an analysis of the receiver operating characteristic curve. Survival analyses were performed using the Kaplan–Meier method. Multivariate regression analyses were performed to reveal the factors predicting pCR. Univariate and multivariate survival analyses were conducted to identify prognostic factors predicting survival. Results: The median follow-up was 38.5 months. pCR was achieved in 41.4% of the patients. In the univariate analyses, the NLR (p = 0.032) and PIV (p = 0.002) were indexes associated with pCR. In the multivariate analysis, the PIV (p = 0.008) was the only index significantly correlated with pCR. According to the multivariate Cox regression analyses, clinical stage 3 (p = 0.032), a pathologic response other than pCR (p = 0.021), and a high LAR (≥4.72) (p = 0.002) were correlated with increased recurrence risk. The univariate Cox regression analyses revealed that failure to achieve pCR (p = 0.037) and the presence of a high LAR (p = 0.044) were significant predictors of overall survival. However, the multivariate analyses failed to identify any significant predictors of death. Conclusions: We found that the PIV was more effective than the other indexes in predicting pCR. To our knowledge, this study is the first to determine an association between the LAR and disease-free survival in patients with breast cancer receiving NAC. We concluded that a high LAR was a poor prognostic factor, especially in patients without a pCR. Therefore, close postoperative monitoring and the intensification of adjuvant treatment should be considered for these patients. However, further studies are needed to confirm our findings.

Oncolytic immunotherapy with nivolumab in muscle-invasive bladder cancer: a phase 1b trial.

There is a critical unmet need for safe and efficacious neoadjuvant treatment for cisplatin-ineligible patients with muscle-invasive bladder cancer. Here we launched a phase 1b study using the combination of intravesical cretostimogene grenadenorepvec (oncolytic serotype 5 adenovirus encoding granulocyte-macrophage colony-stimulating factor) with systemic nivolumab in cisplatin-ineligible patients with cT2-4aN0-1M0 muscle-invasive bladder cancer. The primary objective was to measure safety, and the secondary objective was to assess the anti-tumor efficacy as measured by pathologic complete response along with 1-year recurrence-free survival. No dose-limiting toxicity was encountered in 21 patients enrolled and treated. Combination treatment achieved a pathologic complete response rate of 42.1% and a 1-year recurrence-free survival rate of 70.4%. Pathologic response was associated with baseline free E2F activity and tumor mutational burden but not PD-L1 status. Although T cell infiltration was broadly induced after intravesical oncolytic immunotherapy, the formation, enlargement and maturation of tertiary lymphoid structures was specifically associated with complete response, supporting the importance of coordinated humoral and cellular immune responses. Together, these results highlight the potential of this combination regimen to enhance therapeutic efficacy in cisplatin-ineligible patients with muscle-invasive bladder cancer, warranting additional study as a neoadjuvant therapeutic option. ClinicalTrials.gov identifier: NCT04610671 .

Short-term outcomes of a phase II trial of perioperative capecitabine plus oxaliplatin therapy for advanced gastric cancer with extensive lymph node metastases (OGSG1701).

The prognosis of advanced gastric cancer (GC) with extensive lymph node (LN) metastasis treated with surgery alone remains poor. We conducted a multicenter phase II study to evaluate the efficacy and safety of perioperative capecitabine plus oxaliplatin (CapeOx) therapy in patients with advanced GC with extensive LN metastases. Patients with histologically proven HER2-negative or unknown gastric adenocarcinoma with paraaortic LN (PALN) metastases and/or bulky LN metastases located at the celiac axis, common hepatic artery, and/or splenic artery were included in the study. Patients received three cycles of preoperative CapeOx every 3weeks, followed by five cycles of postoperative CapeOx after gastrectomy with D2 or D2 + including PALN dissection. The primary endpoint was the response rate (RR) according to the RECIST v1.0 criteria. Thirty patients from 14 institutions were enrolled from September 2017 to June 2022. Complete response, partial response, stable disease, and progressive disease occurred in zero, 20, eight, and one patient, respectively. One patient was not evaluated. The RR was 66.7% (90% confidence interval, 50.1-80.7%; one-sided P = 0.049). The preoperative chemotherapy completion rate and the curative resection rate were 96.7% and 93.3%, respectively. The minor (grade ≥ 1b) pathological RR was 66.7%. Grade 3 adverse events of preoperative chemotherapy included neutropenia in 3.3%, anemia in 6.7%, and anorexia in 10.0%. One treatment-related death occurred due to postoperative complications. Preoperative CapeOx chemotherapy showed a favorable RR, curative resection rate, and acceptable adverse events in patients with advanced GC with extensive LN metastasis. UMIN000028749 and jRCTs051180186.

Immunohistochemical Status Predicts Pathologic Complete Response to Neoadjuvant Therapy in HER2-Overexpressing Breast Cancers.

Human epidermal growth factor receptor 2 (HER2) overexpression (HER2+) is defined by immunohistochemistry (IHC) and in situ hybridization (ISH) as IHC3+ or IHC2+/ISH+. Response differences to neoadjuvant anti-HER2 therapy (NT) in IHC3+ versus IHC2+/ISH+ breast cancer patients are poorly characterized. We explored whether pathologic complete response (pCR) varies by HER2 IHC status. Patients with stage I-III HER2+ breast cancer undergoing NT and surgery between 2013 and 2020 were identified from the National Cancer Database and stratified by IHC status. Breast and nodal pCR were analyzed. Of 40,711 HER2+ patients, 83% were IHC3+ and 17% were IHC2+/ISH+. IHC3+ patients were more likely to be hormone receptor (HR)-negative (33 vs. 21%), have cT3/4 tumors (24 vs. 21%), and be cN+ (52 vs. 47%; all p < 0.0001). Breast conservation rates were similar (each 43%, p = 0.32), although IHC3+ axillary lymph node dissection rates were lower (41 vs. 45%, p < 0.0001). Among all patients, breast pCR was 49%, while nodal pCR was 64%. Compared with IHC2+/ISH+, IHC3+ had higher unadjusted breast (54 vs. 22%, p < 0.0001) and nodal (69 vs. 37%, p < 0.0001) pCR rates. When stratified by HR status, pCR was lower for HR+ disease but remained higher among IHC3+ patients. Analysis of T1cN0 primaries mirrored these trends. In multivariable analysis, IHC3+ remained an independent predictor of breast (odds ratio [OR] 3.91, confidence interval [CI] 3.65-4.19, p < 0.0001) and nodal (OR 3.40, CI 3.12-3.71, p < 0.0001) pCR. HER2 IHC status predicts pCR and may help select breast cancer patients who derive the greatest benefit from NT. These findings provide further evidence that revision of HER2 classification may improve clinical management.

Role of Eosinophils in Immunity, Allergy, and Inflammation: Friend or Foe

Eosinophils are multifunctional granulocytes involved in both protective and pathological immune responses. Traditionally recognized for their role in host defense against parasitic infections, eosinophils have gained significant attention for their involvement in allergic diseases, such as asthma, allergic rhinitis, and atopic dermatitis, where they are often considered detrimental. Eosinophils contribute to tissue damage and inflammation by releasing cytotoxic granule proteins, cytokines, and chemokines, perpetuating chronic inflammation. In conditions such as eosinophilic gastrointestinal disorders and hypereosinophilic syndrome, eosinophils infiltrate tissues and exacerbate inflammation, leading to organ dysfunction. However, eosinophils also exhibit beneficial roles, including modulating immune responses, promoting tissue repair, and maintaining tissue homeostasis. Recent research has highlighted their regulatory functions, where they interact with other immune cells to mediate both pro- and anti-inflammatory responses. The dual nature of eosinophils—both as protectors in immunity and contributors to pathology—presents a complex challenge in understanding their full impact on health and disease. Advances in biologic therapies targeting eosinophil activity, such as IL-5 inhibitors, offer promising treatment options for eosinophil-associated disorders. This review explores the diverse roles of eosinophils in immunity, allergy, and inflammation, examining both their protective and harmful functions, while discussing therapeutic strategies aimed at modulating eosinophil activity in various diseases. Keywords: Eosinophils, allergy, inflammation, immune regulation, IL-5 therapy

Efficacy of Mammographic Artificial Intelligence-Based Computer-Aided Detection in Predicting Pathologic Complete Response to Neoadjuvant Chemotherapy

This study evaluates the potential of an AI-based computer-aided detection (AI-CAD) system in digital mammography for predicting pathologic complete response (pCR) in breast cancer patients after neoadjuvant chemotherapy (NAC). A retrospective analysis of 132 patients who underwent NAC and surgery between January 2020 and December 2022 was performed. Pre- and post-NAC mammograms were analyzed using conventional CAD and AI-CAD systems, with negative exams defined by the absence of marked abnormalities. Two radiologists reviewed mammography, ultrasound, MRI, and diffusion-weighted imaging (DWI). Concordance rates between CAD and AI-CAD were calculated, and the diagnostic performance, including the area under the receiver operating characteristics curve (AUC), was assessed. The pre-NAC concordance rates were 90.9% for CAD and 97% for AI-CAD, while post-NAC rates were 88.6% for CAD and 89.4% for AI-CAD. The MRI had the highest diagnostic performance for pCR prediction, with AI-CAD performing comparably to other modalities. Univariate analysis identified significant predictors of pCR, including AI-CAD, mammography, ultrasound, MRI, histologic grade, ER, PR, HER2, and Ki-67. In multivariable analysis, negative MRI, histologic grade 3, and HER2 positivity remained significant predictors. In conclusion, this study demonstrates that AI-CAD in digital mammography shows the potential to examine the pCR of breast cancer patients following NAC.

Neoadjuvant immune checkpoint inhibitor reduced recurrence in operable NSCLC patients with pathological complete response: a retrospective analysis

BackgroundThis study aimed to evaluate if neoadjuvant immune checkpoint inhibitor (ICI) plus chemotherapy (CT) reduced tumor recurrence after surgery than neoadjuvant CT alone in non–small cell lung cancer (NSCLC) patients with pathologic complete response (pCR).MethodsFrom January 1st 2019 to April 30th 2022, 16 NSCLC patients with pCR who received both neoadjuvant ICI and CT were designated as ICI/CT group. Another 8 patients, who received neoadjuvant CT alone, were designated as CT group. The tumor recurrence and patients’ survival status were analyzed.ResultsSquamous cell carcinoma was the predominant histology type in both groups. The CT group had higher percentage of patients who received adjuvant CT than the ICI/CT group (100% vs. 75%, p = 0.046). All patients had been followed up for at least 20 months. At 20 months after surgery, the ICI/CT group had a tumor recurrence rate of 6.25%, which was significantly lower than 37.5% recurrence rate of the CT group. One patient of the CT group died of gastrointestinal hemorrhage and severe anemia at 11 months after surgery, and no patient in the ICI/CT group died. During adjuvant therapy, the ICI/CT group had significantly lower risk of anemia (12.5% vs. 50%) than the CT group (p = 0.046).ConclusionThe study found that in NSCLC patients with pCR, neoadjuvant ICI reduced tumor recurrence rate. This indicated that like in advanced stage NSCLC, the ICI might bring similar long-term anti-tumor effect in operable NSCLC patients.

Improving treatment outcomes for patients with HER2‑positive breast cancer using neoadjuvant double HER2 blockade

Background. Dual anti-HER2-targeted therapy in breast cancer (BC) significantly increased the rate of pathological complete response (pCR) compared to single blockade when added to chemotherapy. However, limited data exist on the long-term impact on survival of the additional increase in pCR.Aim. To improve recommendations regarding HER2-targeted agents and chemotherapy in the neoadjuvant treatment of BC.Materials and methods. N.N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia took participation in some clinical trials of neoadjuvant treatment of HER2-positive breast cancer, including NeoSphere and NeoALTTO. In multicenter, open-label, phase 2 randomised NeoSphere trial, patients with locally advanced, inflammatory, or early-stage HER2-positive BC were randomly assigned to receive four neoadjuvant cycles of trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) plus docetaxel (75 mg/m2 from every 3 weeks, increasing to 100 mg/m2 from cycle 2 if tolerated) (group A), pertuzumab (420 mg every 3 weeks) and trastuzumab plus docetaxel (group B), pertuzumab and trastuzumab (group C), or pertuzumab and docetaxel (group D). After surgery, patients received three cycles of FEC. Рatients in group C received four cycles of docetaxel prior to FEC, and trastuzumab 6 mg/kg every 3 weeks to complete 1 years treatment. In NeoALTTO trial from 455 patients 154 patients received lapatinib, 149 – trastuzumab, 152 – combination of lapatinib and trastuzumab.Results. Between 2007, and 2009, 417 patients were randomly assigned to group A (107 patients), group B (n = 107), group C (n = 107), or group D (n = 96). At clinical cutoff, 87 patients had disease progression or died. 5-year progressionfree survival rates were 81 % (95 % confidence interval (CI) 71–87) for group A, 86 % (95 % CI 72–91) for group B, 73 % for group C, and 73 % for group D (95 % CI 0.34–1.40). Disease-free survival rates were consistent with progressionfree survival rates and were 81 % (95 % CI 72–88) for group A, 84 % (95 % CI 72–91) for group B, 80 % (95 % CI 70–86) for group C, and 75 % (95 % CI 64–83) for group D. In NeoALTTO trial patients who achieved pCR had longer progressionfree survival (85 % (95 % CI 76–91)) compared with patients who did not achieve pCR (76 % (95 % CI 71–81)).Conclusion. High levels of progression-free survival and disease-free survival at 5–10-years follow-up show large and overlapping CI, but support the primary endpoint (pCR) and suggest that neoadjuvant pertuzumab is beneficial when combined with trastuzumab and docetaxel. Additionally, they suggest that pCR could be an early indicator of long-term outcome in early-stage HER2-positive BC.

Active surveillance in patients with a complete clinical response after neoadjuvant chemoradiotherapy for esophageal- and gastroesophageal junction cancer

Abstract Neoadjuvant chemoradiotherapy in patients with esophageal- and gastroesophageal junction cancer induces tumor regression. In approximately one fourth of patients, this leads to a pathological complete response in the resection specimen. Hence, active surveillance may be an alternative strategy in patients without residual disease after neoadjuvant chemoradiotherapy. Previous studies have shown that the combination of esophagogastroduodenoscopy with bite-on-bite biopsies, endoscopic ultrasound with fine needle aspiration of suspected lymph nodes, and a PET-CT-scan can be considered adequate for the detection of residual disease. So far, it has been unclear whether active surveillance with surgery as needed is a safe treatment option and leads to non-inferior overall survival compared to standard esophagectomy after neoadjuvant chemoradiotherapy. This review will discuss the current status of active surveillance for esophageal and junctional cancer.

An explainable longitudinal multi-modal fusion model for predicting neoadjuvant therapy response in women with breast cancer

Multi-modal image analysis using deep learning (DL) lays the foundation for neoadjuvant treatment (NAT) response monitoring. However, existing methods prioritize extracting multi-modal features to enhance predictive performance, with limited consideration on real-world clinical applicability, particularly in longitudinal NAT scenarios with multi-modal data. Here, we propose the Multi-modal Response Prediction (MRP) system, designed to mimic real-world physician assessments of NAT responses in breast cancer. To enhance feasibility, MRP integrates cross-modal knowledge mining and temporal information embedding strategy to handle missing modalities and remain less affected by different NAT settings. We validated MRP through multi-center studies and multinational reader studies. MRP exhibited comparable robustness to breast radiologists, outperforming humans in predicting pathological complete response in the Pre-NAT phase (ΔAUROC 14% and 10% on in-house and external datasets, respectively). Furthermore, we assessed MRP’s clinical utility impact on treatment decision-making. MRP may have profound implications for enrolment into NAT trials and determining surgery extensiveness.

Dynamics of cell-free tumor DNA correlate with early MRI response during chemoradiotherapy in rectal cancer

BackgroundIn locally advanced rectal cancer, the prediction of tumor response during and after neoadjuvant treatment remains challenging. In terms of organ preservation, adaptive radiotherapy, and intensified (total) neoadjuvant therapies, biomarkers are desirable for patient stratification.MethodsIn 16 patients, weekly blood samples (n = 86) to detect cell-free tumor DNA (ctDNA) during long-course neoadjuvant chemoradiotherapy were analyzed. Data were correlated with initial tumor volumes, MRI response in week 2 and 5 of radiotherapy as well as with pathologic tumor response after resection and outcome parameters.ResultsMost patients showed decreasing ctDNA during the course of radiochemotherapy. However, we found heterogenous dynamics of ctDNA and could identify three groups: (1) decline (2) no clear decline and/or late shedding (3) persistence of ctDNA. In seven patients we could detect significant amounts of ctDNA in week 5 or week 6 of treatment. In our pilot cohort, we did not find significant correlations of ctDNA dynamics with pathologic response or outcome parameters. However, patients with distinct decline of ctDNA had larger tumor volumes prior to treatment, and MRI imaging in week 2 and 5 revealed bigger absolute decrease of tumor volumes. If significant levels of ctDNA were found in week 5 and / or 6, patients showed less absolute tumor volume decrease in week 2 and 5.ConclusionsWeekly measurement of ctDNA during radiochemotherapy is feasible and might represent a promising biomarker. Bigger initial primary tumors showed different ctDNA shedding profiles compared with smaller primary tumors and correlations of ctDNA dynamics with early imaging response were found.