Nodal Response Research Articles

Diagnostic accuracy of FDG-PET-CT for the determination of parasternal lymph node response to neoadjuvant chemotherapy in breast cancer patients

Diagnostic accuracy of FDG-PET-CT for the determination of parasternal lymph node response to neoadjuvant chemotherapy in breast cancer patients

Abstract C013: Single cell analysis reveals tumor size-driven immune changes in primary breast tumors and corresponding lymph nodes

Abstract Introduction A sentinel lymph node is the primary node draining the tumor and is likely affected early in the metastatic process. The sentinel node holds a key position in the immune response against tumor in breast and represents a unique connection between the tumor and the host immune response. Detection of lymph node metastasis is important for staging a patient’s disease and is closely associated with prognosis. Although the clinical significance is debated, isolated tumor cells (<0.2 mm) appear to have no impact on survival while macro-metastasis (>2 mm) are linked to a poorer prognosis. Alterations in the immune response in lymph nodes with large versus small metastases have been observed, but little is known about the relationship between the immune response in the primary tumor and the metastatic status of the corresponding lymph nodes. Methods We analyzed single-cell suspensions from primary tumors and lymph nodes of 38 patients with early, operable breast cancer enrolled in the OSLO2 clinical observational trial using mass cytometry with a 47- antibody immune panel (including PanKeratin and EpCAM). In total 3.7 million single cells were analyzed and clustered into 40 metaclusters using FlowSOM. A second set of 22 metastatic lymph nodes from the OSLO2 cohort was used to validate results form the metastatic tumor cells. Additionally, immunofluorescence with E-cadherin and PanKeratin was applied, and intensity measured in 4 metastatic lymph nodes and imaging mass-cytometry was applied on one metastatic lymph node Results We found that the immune microenvironment in primary tumor was dominated by CD4 and CD8 T cells, particularly of exhausted and memory phenotype and with a higher frequency of activated regulatory T cells (Treg). In contrast, the immune composition in lymph nodes was predominantly composed of naturally occurring naive B and T cells. Notably, in line with previous publications we observed a skewing towards memory and exhausted phenotype in T cells, along with increased abundance of activated Treg in lymph nodes with larger metastasis to those with smaller or no metastasis. Furthermore, there were no correlation between the immune profile in the primary tumor and corresponding lymph node. The immune profile in the primary tumor was influenced by tumor size, with larger tumors showing a higher frequency of activated Tregs and exhausted CD8 T cells. Furthermore, In situ analysis revealed that the microenvironment in smaller metastase had an mesenchymal phenotype, while larger tumor deposits exhibited a more epithelial-like phenotype. ConclusionThe immune profile of the primary tumor did not predict the immune profile or metastatic status of the corresponding lymph node. Tumor size in both primary tumors and metastatic lymph nodes is the main drivers of changes in immune cell composition. Tumor cells from smaller metastases exhibited an mesenchymal phenotype, while larger metastasis displayed an epithelial phenotype. Citation Format: Inga Hansine H. Rye, Marit Otterlei Fjørtoft, Inger Riise Bergheim, Karin Teien Lande, Kanutte H. Huse, June Helen H. Myklebust, Ole Christian H. Lingjærde, Øystein. Garred, Jon H. Lømo, Hege H. Russnes. Single cell analysis reveals tumor size-driven immune changes in primary breast tumors and corresponding lymph nodes [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C013.

Seismic Damage Identification Using a Combination of Mixture of Gaussian and Harris Hawks Optimization

ABSTRACTThe present study aims to identify damage in structures using seismic responses and a two‐stage method based on mixture of Gaussian (MOG) and Harris hawks optimization (HHO). Two‐dimensional (2‐D) frame structures under seismic loads are simulated using the finite element method (FEM). The placement of sensors is optimized using a combination of an iterated improved reduced system (IIRS) and the binary differential evolution (BDE) algorithm. The MOG classifier is trained to find the damaged story and damaged element type (i.e., whether it is a beam or a column) using the nodal acceleration responses at the optimal sensor placement of the seismically loaded structure. Thus, as the first step, the possibly damaged elements are located through the classifier. Then, in the second step, the damage is accurately located and quantified by HHO algorithm. The performance of the proposed method is assessed using the numerical results of 2‐D frames of 7 and 14 stories in different damage scenarios with and without considering noise. As a result, the efficiency of the proposed method for the seismic damage identification of 2‐D frames is revealed. Sensor positions are well optimized, and it causes the method to be highly effective. Moreover, MOG correctly finds a damaged story and identifies whether a damaged element is a beam or a column. Damage in the presence of noise is also localized and quantified precisely by HHO.

Mycophenolate Mofetil, an Inhibitor of Inosine Monophosphate Dehydrogenase, and Tofacitinib, a Janus Kinase Inhibitor, Attenuate Airway Inflammation and Hyperresponsiveness in a Mouse Model of Allergic Asthma.

Treatment-resistant asthma remains an unresolved clinical problem and a challenge for current medical science. Consequently, there is a growing and urgent need to develop novel or alternative therapeutic options for the treatment of asthma. The research problem raised in this study was to assess and compare mycophenolate mofetil (MMF), an inhibitor of inosine monophosphate dehydrogenase, and tofacitinib (TFB), a Janus kinase inhibitor, for anti-asthmatic properties, and consequently to determine whether these agents may have potential as alternative options for treatment of allergic asthma. For this purpose, we assessed the effect of administration of MMF and TFB on the development of a mouse model of allergic airway inflammation (AAI) and accompanying CD4+ (cluster of differentiation 4) T-cell immune response in the lung-draining mediastinal lymph nodes (MLNs) and lungs, i.e., in the inductive and effector sites, respectively, of the immune response underlying the development of allergic asthma. The results from a histopathological scoring system demonstrated that the administration of MMF and TFB did not prevent or abolish ovalbumin-induced AAI, but strongly attenuated its severity. The pulmonary function tests revealed that the treatment with MMF and TFB significantly reduced methacholine-induced bronchoconstriction. These results indicate that the treatment with TFB and MMF attenuated the development of ovalbumin-induced AAI. The magnitude of the anti-asthmatic effect was comparable between both agents. The study revealed that the impairment of the clonal expansion of effector CD4+ T cells in the MLNs is a critical event in the mechanism underlying the anti-asthmatic effect of MMF and TFB. Apart from this, the findings of the study strongly suggest that the suppression of the interleukin-33/suppression of tumorigenicity-2 signaling pathway may constitute an additional mechanism responsible for producing this effect. In turn, the results indicate that the anti-asthmatic action induced by the studied agents is not mediated by the generation of forkhead box protein 3-expressing CD4+ regulatory T cells. Clinical implication of the results: the results suggest that MMF and TFB may exert anti-asthmatic action, and thus they may be considered therapeutic options for the treatment of allergic asthma cases resistant to conventional/existing treatment.

Predicting nodal response to neoadjuvant treatment in breast cancer with core biopsy biomarkers of tumor microenvironment using data mining.

To generate a model for predicting nodal response to neoadjuvant systemic treatment (NAST) in biopsy-proven node-positive breast cancer patients (cN+) that incorporates tumor microenvironment (TME) characteristics and could be used for planning the axillary surgical staging procedure. Clinical and pathologic features were retrospectively collected for 437 patients. Core biopsy (CB) samples were reviewed for stromal content and tumor-infiltrating lymphocytes (TIL). Orange Datamining Toolbox was used for model generation and assessment. 151/437 (34.6%) patients achieved nodal pCR (ypN0). The following 5 variables were included in the prediction model: ER, Her-2, grade, stroma content and TILs. After stratified tenfold cross-validation, the logistic regression algorithm achieved and area under the ROC curve (AUC) of 0.86 and F1 score of 0.72. Nomogram was used for visualization. We developed a clinical tool to predict nodal pCR for cN+ patients after NAST that includes biomarkers of TME and achieves an AUC of 0.86 after tenfold cross-validation.

Tumor-Infiltrating Lymphocytes in Resected Esophageal and Gastric Adenocarcinomas Do Not Correlate with Tumor Regression Score After Neoadjuvant Chemotherapy: Results of a Case-Series Study.

Background/Objectives: Adenocarcinomas of the esophagogastric junction and stomach present clinical entities with significant cancer-related morbidity and mortality, often requiring multimodal treatments. Preoperative chemotherapy, mainly the FLOT regimen, is increasingly being utilized in the neoadjuvant setting for the treatment of these malignancies, with varying degrees of tumor response. Methods: We conducted a retrospective, single-institution review on 75 patients operated on for adenocarcinoma of the esophagogastric junction and stomach after neoadjuvant FLOT. We investigated whether tumor response correlates with disease response in lymph nodes examined on surgical specimens. We also investigated the role of tumor-infiltrating lymphocytes (TILs) in correlation with primary tumor response and disease response in lymph nodes on pathological specimens. Results: Our results suggest that TILs correlate in a differential manner with regards to primary tumors versus lymph nodes, thus suggesting that there are different biologic processes in place. Conclusions: Our results provide unique evidence on tumor-infiltrating lymphocytes in the adenocarcinoma histology of the esophagogastric junction and stomach and might be important for further studies.

Synergistic Effects of Fructose and Food Preservatives on Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): From Gut Microbiome Alterations to Hepatic Gene Expression.

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health problem closely linked to dietary habits, particularly high fructose consumption. This study investigates the combined effects of fructose and common food preservatives (sodium benzoate, sodium nitrite, and potassium sorbate) on the development and progression of MASLD. Methods: We utilized a human microbiota-associated mouse model, administering 10% fructose with or without preservatives for 11 weeks. Liver histology, hepatic gene expression (microarray analysis), biochemical markers, cytokine profiles, intestinal permeability, and gut microbiome composition (16S rRNA and Internal Transcribed Spacer (ITS) sequencing) were evaluated. Results: Fructose and potassium sorbate synergistically induced liver pathology characterized by increased steatosis, inflammation and fibrosis. These histological changes were associated with elevated liver function markers and altered lipid profiles. The treatments also induced significant changes in both the bacterial and fungal communities and disrupted intestinal barrier function, leading to increased pro-inflammatory responses in the mesenteric lymph nodes. Liver gene expression analysis revealed a wide range of transcriptional changes induced by fructose and modulated by the preservative. Key genes involved in lipid metabolism, oxidative stress, and inflammatory responses were affected. Conclusions: Our findings highlight the complex interactions between dietary components, gut microbiota, and host metabolism in the development of MASLD. The study identifies potential risks associated with the combined consumption of fructose and preservatives, particularly potassium sorbate. Our data reveal new mechanisms that are involved in the development of MASLD and open up a new avenue for the prevention and treatment of MASLD through dietary interventions and the modulation of the microbiome.

Nomogram Predicting Axillary Lymph Node Dissection Omission After Neoadjuvant Chemotherapy for Node-positive Breast Cancer.

To develop an accurate method to predict nodal pathological complete response (ypN0) in patients after neoadjuvant chemotherapy (NAC) for clinically node-positive breast cancer. We included 128 patients with clinically node-positive primary breast cancer who underwent axillary lymph node dissection after NAC. Breast primary tumor clinical complete response (ycT0) was observed in 29.7% and nodal clinical complete response (ycN0) in 44.5% of cases. When ycN0 was predicted as ypN0, the negative predictive value was 77.2%, and the false-negative rate was 19.7%. Estrogen receptor status, ycT0, and ycN0 were independent predictive factors for ypN0 after NAC in patients with clinically node-positive breast cancer. These factors were used to develop a nomogram for ypN0 prediction. The following points were added: 82 in case of estrogen receptor-negative, 56 in case of ycT0, and 100 in case of ycN0. Score summation was used to prognosticate the manifestation of ypN0. Our nomogram predicted ypN0 with a negative predictive value of 92.9% and false-negative rate of 4.5%, demonstrating an approximate 15% improvement over ypN0 prediction using ycN0 alone. Estrogen receptor-negativity, ycT0, and ycN0 are independent predictive factors for ypN0 after NAC in clinically node-positive breast cancer. The nomogram may improve individualized axillary treatment.

PI3 kinase delta governs regulatory T-cell biology and thus confers protection against atherosclerosis progression in mice

Abstract Introduction and Purpose Atherosclerosis is a chronic inflammatory disease of arteries, critically involving innate and adaptive immune cells like macrophages as well as T and B lymphocytes. Macrophages are major drivers of disease through the ingestion of lipoproteins, foam cell formation, and secretion of inflammatory mediators. Although macrophages outnumber other leukocytes in atherosclerotic plaques, T and B cells can shape the course of disease by promoting or mitigating inflammatory responses. The phosphoinositide 3-kinase delta (PI3Kd) exerts a key role in the regulation of immune responses including activation, proliferation, differentiation, and effector function of lymphocytes. Therefore, PI3Kd may represent a promising target for the modulation of inflammatory diseases. Consequently, we aimed to analyse the role of PI3Kd during atherogenesis. Methods and Results To investigate the role of haematopoietic PI3Kd in atherosclerosis, bone marrow from PI3Kd-/- or PI3Kd+/+ mice was transplanted into Ldlr-/- mice. After a 6-weeks-challenge by high fat diet, PI3Kd-/- recipient Ldlr-/- mice displayed profoundly impaired CD4+ and CD8+ T-cell numbers, CD4+ T-cell activation, CD4+ effector T-cell differentiation, and proatherogenic CD4+ T-helper (Th) 1 responses in para-aortic lymph nodes and spleen compared with PI3Kd+/+ transplanted controls. Surprisingly, the net effect of PI3Kd deficiency was a substantial increase of aortic inflammation and atherosclerosis in Ldlr-/- mice. Whereas plaque content and functions of macrophages including foam cell formation, efferocytosis, and cytokine secretion remained largely unaffected, haematopoietic PI3Kd ablation strongly reduced mature B cells and serum immunoglobulins in Ldlr-/- mice. Importantly, PI3Kd deficiency severely impaired numbers, proliferation, immunosuppressive functions, and stability of regulatory CD4+ T cells (Tregs). Consequently, adoptive transfer of PI3Kd+/+ Tregs fully restrained the atherosclerotic plaque burden in PI3Kd-/- transplanted Ldlr-/- mice without affecting B-cell numbers and serum immunoglobulins, whereas transferred PI3Kd-/- Tregs failed to relieve atherosclerosis progression. Conclusions Here, we demonstrate that PI3Kd plays a crucial role in Tregs, Th1 cells, and B cells during atherogenesis. Lack of PI3Kd signalling specifically in atheroprotective Treg responses outplays its impact on B-cell and proatherogenic Th1 responses, thus leading to aggravated atherosclerosis. Hence, PI3Kd is a key regulator of Treg biology and thereby protects against atherosclerosis, suggesting that fine-tuning PI3Kd signalling may represent a promising target for Treg-directed therapy.

Albumin-To-Alkaline Phosphatase Ratio as a New Early Predictive Marker of Axillary Response in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy: A Pilot Study.

Background and Objectives: The Albumin-to-Alkaline Phosphatase ratio (AAPR) is an easily applicable and cost-effective marker investigated as an outcome predictor in solid cancers. Preliminary evidence in breast cancer suggests that a low AAPR correlates with a poor response to neoadjuvant chemotherapy (NAC) in primary tumors. However, data regarding the axillary response are lacking. This study aims to evaluate whether the AAPR can predict the axillary response in initially nodal-positive (cN+) breast cancer patients undergoing NAC. Materials and Methods: Clinical and biochemical variables of cN+ breast cancer patients undergoing NAC were collected. Pre-NAC albumin and alkaline phosphatase serum values were utilized in the AAPR calculation. Fisher's exact test was performed to identify differences between the two groups of patients (high and low AAPR according to the cut-off reported in the literature). The primary outcome was the nodal pathologic complete response (pCR) rate in the two groups of patients. Results: Nodal pCR was achieved in 20/45 (44.4%) patients. A total of 36/45 (80%) patients had an AAPR > 0.583. Among patient and tumor characteristics, the only statistically significant difference between the two groups was the axillary pCR between the low and high AAPR groups (p-value = 0.03, OR = 0.129, 95% CI = 0.00-0.835). Conclusions: This pilot study suggests that the pre-treatment AAPR might be an early predictor of axillary response in cN+ breast cancer patients undergoing NAC. This result justifies further investigation in larger prospective trials to validate this finding.

Trends in management and related outcomes for occult primary breast cancer.

Occult Primary Breast Cancer (OPBC) is a rare clinical condition in which breast cancer is located within the axillary lymph nodes, but no primary tumor is identified in the breast. We evaluated trends of neoadjuvant chemotherapy (NAC) use and subsequent axillary procedures in OPBC as well as outcomes for these patients. The National Cancer Database was used to identify adult women with cT0N1-3M0 breast cancer between 2012 to 2021 that underwent axillary lymph node surgery. Kaplan-Meier curves were used to evaluate survival between groups. 2759 patients met inclusion criteria. 86.2% underwent ALND alone in 2012, and this decreased to 65.6% in 2021. 4.7% underwent SLNB alone in 2012 and this increased to 16.2% in 2021 (p < 0.001). For patients who had undergone NAC, 46.4% of ALND patients had nodal pathologic complete response (nPCR), compared to 42.7% of SLNB + ALND and 66.4% of SLNB only patients. For patients with nPCR, there was no difference in overall survival (OS) between ALND, SLNB + ALND, and SLNB alone groups (p = 0.9912). Most OPBC patients were treated with ALND, with a modest increase towards SLNB use during the study period. There was no difference in OS with respect to axillary surgical procedure in our population for those with nPCR after NAC. This suggests that for carefully selected OPBC patients with an excellent clinical response to NAC and negative SLNB, omission of ALND may be considered.

Pathological responses of primary tumor and lymph nodes in non-small cell lung cancer after neoadjuvant chemoimmunotherapy: a retrospective real-world study.

In patients with non-small cell lung cancer (NSCLC) receiving neoadjuvant chemoimmunotherapy (NCIT), inconsistent pathological responses between the tumor and lymph nodes (LNs) are often observed. There has been limited evidence comparing the different responses of tumors and LNs in those patients. This retrospective real-world analysis intended to evaluate the clinical and pathological response of primary tumors and LNs, and the long-term outcomes in NSCLC patients after NCIT. We included resectable NSCLC patients who had received neoadjuvant therapy and had available clinicopathological records. The progression-free survival (PFS) and overall survival (OS) outcomes were analyzed using survival analysis. In total, 204 patients were included in the final analysis. Patients were predominantly male (85.8%) and ever-smokers (66.2%), with a median age of 63 years. No significant difference was observed in intraoperative bleeding (P=0.51 and P=0.54) and operation time (P=0.57 and P=0.58) between the major pathologic response (MPR) and pathological complete response (pCR) group, respectively. Patients who were male (pCR, P=0.01; MPR, P=0.004), with squamous cell carcinoma (SCC) (pCR, P=0.02; MPR, P=0.001), and overall response rate (ORR) (pCR, P<0.001; MPR, P<0.001) demonstrated significantly higher rates of pCR and MPR. The median follow-up time for all patients in this study was 23 months. Patients with MPR (P=0.004) and pCR (P=0.02) experienced prolonged PFS, but not OS (MPR, P=0.08; pCR, P=0.15). In terms of yield pathological tumor MPR (ypTMPR) and yield pathological LNs stage (ypN), Kaplan-Meier analyses demonstrated that there was a better PFS for the ypTMPR(+)/ypN(0) group, followed by ypTMPR(-)/ypN(0), ypTMPR(+)/ypN(0), and ypTMPR(-)/ypN(1+2) (P=0.01). The average PFS time was 35.7, 31.7, 29.4, and 28.7 months, respectively. After achieving MPR, the probability of local recurrence or distant metastasis was 7.3%, 25%, 23.5%, and 23.7%, respectively. In this real-world study, the combination of tumor and LNs responses was significantly associated with prognosis, and we demonstrated that ypTMPR(+)/ypN(0) group had a better prognosis, followed by ypTMPR(-)/ypN(0), ypTMPR(+)/ypN(0), and ypTMPR(-)/ypN(1+2). We advocate for ypTMPR(+)/ypN(0) status as a better surrogate of PFS in resectable NSCLC patients after NCIT.

Reactive Changes in Lymph Node Structure in Peritonitis and during Treatment with a New Antibiotic.

The effect of a new antibiotic peptomide A-70 on changes in the mesenterial lymph nodes caused by experimental peritonitis was studied. Differences in the morphological changes in rat lymph nodes in peritonitis and against the background of antibiotic therapy were revealed. Lymph nodes responded to peritoneal inflammation by reducing the area of cortical structures and expansion of the sinus system, which indicates a decrease in drainage-detoxification and immune function and determines unfavorable outcome of peritonitis. Antibiotic therapy reduced inflammatory manifestations and toxic pressure on the lymph system and potentiated the reactive response of the mesenteric lymph nodes: the size of lymphoid nodes and the paracortical T-dependent zone increased against the background of shrinkage of the sinus system, which attested to activation of the lymphopoietic function and immune response of lymph nodes in peritonitis. The observed changes attested to favorable prognosis of peritonitis treated with antibiotic peptomide A-70.

Enhanced mucosal SARS-CoV-2 immunity after heterologous intramuscular mRNA prime/intranasal protein boost vaccination with a combination adjuvant

Current COVID-19 mRNA vaccines delivered intramuscularly (IM) induce effective systemic immunity, but with suboptimal immunity at mucosal sites, limiting their ability to impart sterilizing immunity. There is strong interest in rerouting immune responses induced in the periphery by parenteral vaccination to the portal entry site of respiratory viruses, such as SARS-CoV-2, by mucosal vaccination. We previously demonstrated the combination adjuvant, NE/IVT, consisting of a nanoemulsion (NE) and an RNA-based RIG-I agonist (IVT) induces potent systemic and mucosal immune responses in protein-based SARS-CoV-2 vaccines administered intranasally (IN). Herein, we demonstrate priming IM with mRNA followed by heterologous IN boosting with NE/IVT adjuvanted recombinant antigen induces strong mucosal and systemic antibody responses and enhances antigen-specific T cell responses in mucosa-draining lymph nodes compared to IM/IM and IN/IN prime/boost regimens. While all regimens induced cross-neutralizing antibodies against divergent variants and sterilizing immunity in the lungs of challenged mice, mucosal vaccination, either as homologous prime/boost or heterologous IN boost after IM mRNA prime was required to impart sterilizing immunity in the upper respiratory tract. Our data demonstrate the benefit of hybrid regimens whereby strong immune responses primed via IM vaccination are rerouted by IN vaccination to mucosal sites to provide optimal protection to SARS-CoV-2.

ASO Author Reflections: Time to Explore Minimally Invasive Axillary Nodal Staging After Neo-Adjuvant Chemotherapy in Inflammatory Breast Cancer.

In inflammatory breast cancer (IBC), obstructed lymphatics present a barrier to sentinel node biopsy. In theory this challenge could be overcome by clipping the clinically positive node at presentation and surgically retrieving it after neoadjuvant chemotherapy (NAC). If the clipped node accurately reflects the axillary status, then deescalation of axillary nodal dissection could be a possibility in IBC with complete pathological nodal response post-NAC.

413. LYMPH NODE MAJOR PATHOLOGIC RESPONSE IS A POTENTIAL PROGNOSTIC FACTOR AFTER NEOADJUVANT CHEMORADIOTHERAPY IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background Esophageal cancer ranks tenth in incidence and is the sixth most common cause of cancer-related deaths. Neoadjuvant chemoradiotherapy before and after surgery has been shown to improve ESCC patients' survival compared with surgery alone. However, the outcomes of nCRT are heterogeneous, and clinical or pathological methods that can predict nCRT responses have been extensively studied. There are currently no standard grading methods that assess the treatment response in lymph nodes after nCRT. We aimed to assess the clinicopathological relevance and determine the prognostic significance of lymph node major pathologic response (MPR) after nCRT in ESCC patients. Methods Patients who received nCRT for ESCC followed by surgery were retrospectively reviewed and classified into different lymph node stage (LNS) according to their pathological regression: LNS0 (no tumor cells in lymph node before nCRT); LNS1 (residual tumor cells in lymph node after nCRT≤50%; major pathologic response); LNS2 (residual tumor cells in lymph node after nCRT&amp;gt;50%; not major pathologic response). Results In total, 187patients, comprising 91,49 and 47 patients with LNS stage of 0(no tumor cells in lymph node before nCRT),1(major pathologic response), or 2(not major pathologic response), respectively, were included. The result showed that the higher LNS stage was strongly associated with decreased overall survival (P&amp;lt;0.001) and disease-free survival (P&amp;lt;0.001), and increased recurrence risks (P=0.002). The cox regression showed MPR was significantly an independent prognostic factor of OS and DFS. Among 96 patients with clinically positive LNs,54patients (56.3%) showed discordance between the PT and LN pathological regression grades. Conclusions Residual tumor cells in lymph node after nCRT≤50% could be defined as lymph node major complete response. The Lymph node MPR can be an independent prognostic indicator of ESCC patients who received nCRT plus curative surgery.

525. PALLIATIVE MULTIMODALITY-THERAPY, EVEN WITH ABBREVIATED IMMUNOTHERAPY CAN MAKE CURATIVE SURGERY FOR SYNCHRONOUS LUNG AND ESOPHAGEAL CANCER POSSIBLE: A CASE REPORT

Abstract Background Synchronous lung and esophageal carcinomas are problematic. When both cancers are locally advanced, combined surgical treatment is rarely possible because of high-risk or insufficient respiratory reserve. Palliative treatment including immunotherapy can sometimes offer significant tumor response and potentially prolong survival in patients with PDL-1 tumor expression. However the place of immunotherapy for potentially rendering inoperable patients operable is still unknown. Methods Case report: A 78-year-old male with smoking history was diagnosed with synchronous locally advanced adenocarcinoma of the Gastroesophageal Junction (GEJ) cT3cN1cM0 and bilateral lung adenocarcinomas stage 4a, cT2cN1cM1a (right lower lobe 43mm confirmed by CT-guided biopsy, left upper lobe 32mm and additional S6 left lower lobe nodule). The patient was considered incurable by MDT and palliative treatment was offered as both cancers had significant PDL-1 expression (GEJ: CPS score &amp;gt;1, Lung: PDL-1 expression 90%). Pembrolizumab immunotherapy was started but poorly tolerated (severe myositis) and stopped again after only 6 weeks. The left-sided lung cancer had by then already regressed and stereotactic irradiation (SBRT 5x12Gy) of the right-side lung cancer was administered resulting in further local tumor control (figure). Endoscopic tumor re-evalution showed a Siewert type 2 tumor (uT3N1) similar to the initial endoscopy 15 months before. Both side lung adenocarcinomas remained regressed and the left lower lobe nodule was unchanged (6mm). Mediastinal lymph node staging by EBUS was negative. Thirteen months after initial diagnosis, 4 cycles of neo-adjuvant chemotherapy (FLOT) were administered. Combined synchronous surgery was finally done 16 months after initial diagnosis. A minimally invasive combined resection included a laparoscopic &amp; thoracoscopic Ivor-Lewis MIE, left thoracoscopic wedge of the lower lobe nodule and a right lower lobectomy with radical lymph node dissection. Post-operative course was smooth: Clavien-Dindo score 1, hospital stay 18 days. Final pathology Distal third adenocarcinoma (1.5x1.2cm above Z-line) with major partial response ypT2N0M0, R0, 0/43 lymph nodes (subcarinal signs of nodal response), right lower lobe tumor of 60x55mm with residual 1.2mm focus of residual viable adenocarcinoma (ypTisN0M0, R0) and left lower lobe hamartoma (6mm). Follow-up showed no recurrence 9 months after surgery (25 months from initial diagnosis). Conclusions: 1) Despite much abbreviated palliative immunotherapy (6 weeks), SBRT and FLOT our patient was down-staged within 16 months from an initially palliative situation to a potential cure with complete resection of all tumors. 2) Synchronous combined radical laparoscopic &amp; thoracoscopic Ivor-Lewis esophagectomy with lung lobectomy can be feasible after immuno-, chemo- and radiotherapy even in elderly patients.

Multiregional dynamic contrast-enhanced MRI-based integrated system for predicting pathological complete response of axillary lymph node to neoadjuvant chemotherapy in breast cancer: multicentre study

The accurate evaluation of axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) in breast cancer holds great value. This study aimed to develop an artificial intelligence system utilising multiregional dynamic contrast-enhanced MRI (DCE-MRI) and clinicopathological characteristics to predict axillary pathological complete response (pCR) after NAC in breast cancer. This study included retrospective and prospective datasets from six medical centres in China between May 2018 and December 2023. A fully automated integrated system based on deep learning (FAIS-DL) was built to perform tumour and ALN segmentation and axillary pCR prediction sequentially. The predictive performance of FAIS-DL was assessed using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. RNA sequencing analysis were conducted on 45 patients to explore the biological basis of FAIS-DL. 1145 patients (mean age, 50 years±10 [SD]) were evaluated. Among these patients, 506 were in the training and validation sets (axillary pCR rate of 40.3%), 127 in the internal test set (axillary pCR rate of 37.8%), 414 in the pooled external test set (axillary pCR rate of 48.8%), and 98 in the prospective test set (axillary pCR rate of 43.9%). For predicting axillary pCR, FAIS-DL achieved AUCs of 0.95, 0.93, and 0.94 in the internal test set, pooled external test set, and prospective test set, respectively, which were also significantly higher than those of the clinical model and deep learning models based on single-regional DCE-MRI (all P<0.05, DeLong test). In the pooled external and prospective test sets, the FAIS-DL decreased the unnecessary axillary lymph node dissection rate from 47.9% to 6.8%, and increased the benefit rate from 52.2% to 86.5%. RNA sequencing analysis revealed that high FAIS-DL scores were associated with the upregulation of immune-mediated genes and pathways. FAIS-DL has demonstrated satisfactory performance in predicting axillary pCR, which may guide the formulation of personalised treatment regimens for patients with breast cancer in clinical practice. This study was supported by the National Natural Science Foundation of China (82371933), National Natural Science Foundation of Shandong Province of China (ZR2021MH120), Mount Taishan Scholars and Young Experts Program (tsqn202211378), Key Projects of China Medicine Education Association (2022KTM030), China Postdoctoral Science Foundation (314730), and Beijing Postdoctoral Research Foundation (2023-zz-012).

Nodal Response and Survival After Neoadjuvant Endocrine Therapy in Hormone Receptor-Positive Breast Cancer: 20-Year Experience from a Single Institution.

Axillary response to neoadjuvant endocrine therapy (NET) for the treatment of hormone receptor-positive breast cancer (HR+ BC) is not well-described. This study was designed to characterize nodal response after NET. Patients receiving NET followed by curative intent surgery at a comprehensive cancer center from 1998 to 2022 in a prospectively collected registry were included. Patients with distant metastasis were excluded. Primary outcome was nodal pathologic complete response (pCR). Downstaging was defined as post-NET decrease in category. We included 123 patients; the majority were cT2 (n = 59) or cT3 (n = 35), and cN0 (n = 81). Median age was 70.0 years (interquartile range 62.1-76.0). Forty-two patients (34.1%) were clinically node-positive. After NET, 73 (59.8%) underwent breast-conserving surgery. All patients underwent sentinel lymph node biopsy, and 12 (9.8%) underwent completion axillary lymph node dissection. In-breast downstaging was achieved in 51 (41.5%) patients, 1 (0.8%) had breast pCR, and 14 (11.4%) had breast upstaging. Axillary downstaging was achieved in 10 (23.8%), 6 patients (14.3%) had nodal pCR, and 14 (33.3%) had axillary upstaging. At 10-year follow-up, local recurrence was 1% and distant recurrence was 14%, while disease-free survival was 82%. After adjusting for demographic and clinical factors, age was the only characteristic associated with mortality (hazard ratio 1.07, 95% confidence interval 1.01-1.13). In HR+ BC treated with NET, long-term disease-free survival is good, although nodal pCR is uncommon for cN+ patients. Future studies are needed to elucidate optimal neoadjuvant systemic therapy and to delineate oncologically safe strategies to deescalate axillary management for residual microscopic disease.

The prognostic value of lymph node response to neoadjuvant therapy among breast cancer subtypes

Objectives. The aim of this study was to assess the prognostic value of persistent node involvement after neoadjuvant chemotherapy among breast cancer subtypes. Materials and methods. A total of 258 patients with T1-T4 and N0-N3 breast cancer treated by neoadjuvant chemotherapy followed by tumor excision and axillary lymph-node dissection between January 2015 and December 2019 were selected from the Coltea Clinical Hospital database and retrospectively evaluated. Association between nodal involvement (ypN) binned into four classes (0, 1-3, 4-9 and &gt;10), relapse free-survival and overall survival among the whole population and according to breast cancer subtypes was analyzed using Statistical Package for Social Science Version 29.0.2.0. Outcomes. After a median follow-up of 20.7 months (range 1-97 months) post neoadjuvant chemotherapy nodal involvement was significantly associated with disease free survival in the whole population (X2(3)= 23.161, p &lt;.001) and between breast cancer subgroups (X2(3) = 27.871, p= &lt;.001). After univariate cox regression analyses by breast cancer subtypes nodal involvement was statistically significant only in the Luminal B(HER-) (X2(3)=14.867, p=.002) and triple-negative breast cancer (X2(3)= 9.867, p=.020). In Luminal B(HER2-) breast cancers all nodal involvement subgroups were associated with impaired relapse free survival compared to ypN0 tumors (1-3 nodes, HR= 4.871, 95%CI [1.32-17.94], p=.017; 4-9 nodes, HR=5.126, 95%CI [1.341-19.59], p=.017; &gt;10 nodes, HR=8.744, 95%CI [2.379-32.13], p=.001). In triple negative breast cancers, relapse-free survival was associated with an adverse prognosis in patients with more than 10 nodes involved when compared with ypN0 (HR=16.57, 95%CI [3.25-84.30], p=&lt;.001). There was no statistically significant association in the univariate cox regression analyze between post neoadjuvant chemotherapy nodal involvement and overall survival neither in the whole population (X2(3)=.992, p=.803) nor among breast subtypes (X2(3)=1.191, p= .779). Kaplan Meier analyze of RFS adjusted for BC subtype showed a statistically significant relapse rate in all groups (1-3 (p=.035), 4-9(p=&lt;.001), &gt;10 (p=&lt;.001)) compared with ypN0 group. Kaplan Meier overall survival analyze showed no statistical difference in survival among node groups. Conclusions. Post neoadjuvant chemotherapy lymph node status in breast cancer subtypes represents an important prognostic factor of relapse-free survival and the prognostic value of residual axillary disease should be interpreted according to breast cancer subtype.