Neoadjuvant Research Articles

Pretreatment plasma vitamin D and response to neoadjuvant chemotherapy in breast cancer: evidence from pooled analysis of cohort studies

Background: Biological evidence has revealed anti-tumor effect of vitamin D, but whether it could predict the response to neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients remains inconclusive. The aim was to investigate the association between pretreatment vitamin D level and response to NAC and subsequent survival outcomes in BC patients. Materials and Methods: We systematically searched the Medline, Embase, Cochrane Library and Web of Science databases and clinical trial registries to identify relevant articles from inception to October 8, 2024. Eligible studies investigating the associations between pretreatment plasma vitamin D and response to NAC in BC patients were selected according to the predefined criteria, with the study characteristics extracted by two reviewers. The primary outcome was pathological complete response (pCR), while overall pathological response and event-free survival (EFS) were adopted as secondary outcomes. Summary effect estimates of odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Subgroup and sensitivity analyses were performed based on study characteristics and methodological quality. Results: Six retrospective cohort studies involving 1,291 BC patients were included. We observed a significant association between pretreatment vitamin D deficiency and 50% increased odds of non-pCR after NAC (OR=1.50, 95%CI 1.11-2.03, P=0.008) with no heterogeneity (I2=0%). We also identified a significant association of vitamin D with overall pathological response (OR=1.33, 95%CI 1.01-1.75, P=0.046). A similar association with EFS (HR=1.27, 95%CI 0.92-1.75, P=0.139) was also noted although the effect estimate was not statistically significant. Sensitivity analyses based on methodological quality showed consistent findings. Conclusion: Pretreatment vitamin D deficiency is associated with an inferior response to NAC in BC patients. Our meta-analysis advocates further prospective studies with large sample sizes before vitamin D supplementation could be administered to improve NAC response and subsequent prognosis of BC patients.

Correlation Between Grade of Clinical Response to Neoadjuvant Therapy for Rectal Cancer and Oncologic Outcomes in the Era of Watch-and-Wait

Background: The watch-and-wait strategy provides an opportunity to pursue non-operative management in rectal cancer patients with clinical complete response after neoadjuvant therapy. The management of those with near complete response remains controversial. Objective: We assessed the oncologic outcomes of patients managed by watch-and-wait versus total mesorectal excision according to clinical response to neoadjuvant therapy. Design: Retrospective cohort study. Settings: Comprehensive cancer center in New York. Patients: Patients with rectal adenocarcinoma diagnosed between January 2006 to December 2020. Interventions: A watch-and-wait strategy of active surveillance was offered to patients if they achieved clinical complete response. Salvage surgery was utilized for watch-and-wait patients with local regrowth. Patients with an incomplete response underwent total mesorectal excision Main Outcome Measures: Local regrowth rate, organ preservation rate, disease-free survival and overall survival. Results: Patients with rectal adenocarcinoma (n = 1230) were divided into 3 response cohorts—incomplete (n = 646), near-complete (n = 189) and complete (n = 395). Eighty-one (43%) patients in the near-complete group and 351 (89%) patients in the complete group entered watch-and-wait. Three-year local regrowth rates were 40% and 24% in the near-complete and complete response cohorts, respectively. The 5-year organ preservation rate was 53% in near-complete responders, and 73% in complete responders. Five-year disease-free survival increased with greater clinical response to neoadjuvant therapy with intermediate outcomes noted for patients with a near-complete (73%) compared to complete (82%) or incomplete response (68%). Overall survival at 5 years was similar between the three cohorts (complete 90%, near-complete 86%, and incomplete 85%). Limitations: Retrospective nature. Conclusion: Greater clinical response to neoadjuvant therapy is associated with improved oncologic outcomes. Near-complete responders may avoid surgery and still achieve high organ preservation rates yet experience greater local regrowth rates than clinical complete response patients. Ongoing prospective trials integrating watch-and-wait after complete response as determined by uniform criteria will bolster the work to help treating physicians better select patients who qualify for active surveillance. See Video Abstract.

Correction: Role of neoadjuvant chemotherapy in patients with locally advanced and clinically positive nodes Upper Tract Urothelial Carcinoma treated with Nephroureterectomy: real-world data from the ROBUUST 2.0 Registry

Correction: Role of neoadjuvant chemotherapy in patients with locally advanced and clinically positive nodes Upper Tract Urothelial Carcinoma treated with Nephroureterectomy: real-world data from the ROBUUST 2.0 Registry

A Case of Cutaneous Squamous Cell Carcinoma Treated with Neoadjuvant Cemiplimab

We present a case describing the successful treatment of a 68-year-old male with high-risk cutaneous squamous cell carcinoma (cSCC) using neoadjuvant cemiplimab. The patient presented with a rapidly growing papule on the left hand, which was initially treated with wide local excision and subsequently developed axillary lymphadenopathy. After radiation therapy led to complications, the patient received four cycles of cemiplimab, resulting in significant tumor necrosis and minimal residual disease. This case underscores the potential of cemiplimab as a neoadjuvant therapy for cSCC, offering an effective treatment with fewer adverse effects compared to traditional therapies. The report highlights the importance of a multidisciplinary approach in optimizing outcomes for patients with advanced cSCC.

Features of Lateral Pelvic Lymph Nodes Associated With Pathological Involvement After Total Neoadjuvant Therapy in Patients Undergoing Lateral Pelvic Lymph Node Dissection

BACKGROUND: There is a lack of consensus regarding treating involved lateral pelvic lymph nodes in rectal cancer. OBJECTIVE: This study aimed to evaluate the clinical and magnetic resonance imaging-based factors associated with pathological lateral pelvic lymph node metastasis in patients undergoing total neoadjuvant therapy and lateral pelvic lymph node dissection. DESIGN: This is a retrospective study. SETTINGS: This study was conducted at a single comprehensive cancer center. PATIENTS: A total of 107 patients with advanced low rectal cancer with pretreatment enlarged lateral pelvic lymph nodes (≥7 mm in long-axis) undergoing total neoadjuvant therapy with long-course chemoradiotherapy, followed by total mesorectal excision and lateral pelvic lymph node dissection, were enrolled. MAIN OUTCOME MEASURES: Pathological lateral pelvic lymph node metastasis and survival. RESULTS: Among 107 patients, 48 had a short-axis lateral node diameter <7 mm at baseline, while 59 had ≥7 mm. The ≥7 mm group showed significantly higher rates of pathological lateral pelvic lymph node metastasis (44.1% vs. 2.1%; p < 0.0001). In this group, pathological lateral pelvic lymph node metastasis was independently associated with pre-treatment malignant features and post-treatment short-axis diameter ≥4 mm. Five-year relapse-free survival was significantly lower in patients with post-treatment lateral node diameter ≥ 4 mm than those with <4 mm (71.1% vs. 86.2%, p = 0.0364). Patients with pathological lateral pelvic lymph node metastasis had significantly lower overall survival, relapse-free survival, and local recurrence-free survival rates. LIMITATIONS: Selection bias exists in a retrospective analysis. CONCLUSIONS: Pathological lateral pelvic lymph node metastasis is rare in patients with pre-treatment short-axis diameter <7 mm. In patients with pre-treatment short-axis diameter ≥7 mm, pre-treatment malignant features and post-treatment short-axis diameter are both associated with pathological lateral pelvic lymph node metastasis. These factors should be considered when deciding whether to proceed with lateral pelvic lymph node dissection after total neoadjuvant therapy. See Video Abstract.

Abstract C032: The impact of neoadjuvant endocrine therapy (NET) in ER+ breast cancer tumor microenvironment and metastasis

Abstract Breast cancer is the most common cancer in women worldwide and the second leading cause of death. The Estrogen Receptor positive (ER+) subtype constitutes approximately 80% of the yearly 250,000 breast cancer diagnoses in the US. Anti-estrogen endocrine therapy, administered either pre- or post-operatively, is the cornerstone treatment for all stages of breast cancer. Pre- operative or neoadjuvant endocrine therapy (NET) reduces pre-surgical tumor burden, improves surgical outcome, and provides prognostic information. Although the treatment often has a favorable initial response, about 20% of patients eventually develop resistance and recurrent disease, even decades after the primary diagnosis.We hypothesized that resistance in NET is mediated through pro-metastatic changes in the tumor microenvironment affecting either (i) dissemination machinery or (ii) cancer cell phenotype.The main mode of breast cancer hematogenous dissemination to distant sites is through intravasation portals called Tumor Microenvironment of Metastasis (TMEM) doorways. Each TMEM doorway consists of a tumor cell overexpressing the actin-regulatory protein MENA, a Tie2high/ VEGFAhigh macrophage and an endothelial cell, all in direct contact. TMEM doorway activity leads to vascular opening events, during which tumor cells located in areas around TMEM doorways intravasate and disseminate to secondary sites. Therefore, to investigate the impact of NET on cancer cell dissemination, we evaluated its effect on (i) TMEM doorway score (the number of TMEM doorways per tissue area), (ii) TMEM doorway opening, (iii) the number of circulating tumor cells and (iv) the number of disseminated tumor cells. We used the orthotopic MCF7 breast cancer xenograft model grown in NOD/SCID mice and tested two drugs widely used in NET, Fulvestrant (a Selective Estrogen Receptor Degrader) and Tamoxifen (a Selective Estrogen Receptor Modulator). NET did not affect the TMEM doorway score, TMEM doorway activity, the number of CTCs or the number of DTCs. We are now focused on evaluating the effect of NET on the density of cancer cells which are upregulated in programs of invasion, stemness, and dormancy. This “Triple Threat Phenotype (TTP)” gives tumor cells an enhanced ability to disseminate to and colonize distant organs. To this effect we will stain primary MCF7 tumors from NET and vehicle-treated mice for markers of invasiveness (MENA), stemness (SOX9) and dormancy (NR2F1). Detecting any changes in the phenotype of metastatic tumor cells following NET will help us understand underlying mechanisms of endocrine therapy resistance and may lead to new therapeutic targets and improve patient outcomes. Citation Format: Anastasia Aristoteleia Chondronikola, Dimitra Anastasiadou, Aliona Zintiridou, Camille L. Duran, Nicole Barth, Burcu Karadal-Ferrena, Erika Pereira-Zambalde, Lina Ariyan, Suryansh Shukla, George S. Karagiannis, David Entenberg, John S. Condeelis, Maja H. Oktay. The impact of neoadjuvant endocrine therapy (NET) in ER+ breast cancer tumor microenvironment and metastasis [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 C032.

Effects on lymph node size, staging and primary tumor histology on diagnostic accuracy of axillary lymph node aspirate of breast cancers.

Fine-needle aspiration cytology is preferred for axillary lymph node metastasis with low costs and minimal risks. To improve diagnostic performance by incorporating clinical-radiological-pathological parameters, a large cohort pre-operative aspirates in were reviewed for parameters affecting adequacy rate and accuracy. Axillary nodal aspirates from three institutions with histologic correlation were retrieved. Case notes were reviewed for parameters pertaining to the primary tumor, nodal status, histologic and cytologic diagnoses. Totally 1361 specimens were included. The risk of malignancy for C1-C5 categories were 53.39%, 27.45%, 70.97%, 83.33% and 88.00%, increasing to 75.86%, 94.59% and 99.28% for C3/C4/C5 categories excluding cases with neoadjuvant therapy. Node size (p < 0.001) and histologic grade (p = 0.003) of primary tumor positively correlated with specimen adequacy. Presence of in situ component trended towards inadequacy (p = 0.069). Lymph node size remained a strong predictor of concordant cytologic diagnosis (p < 0.001). A higher percentage of involved node (p = 0.006) and HER2 overexpressed breast cancers (p = 0.027) increased concordance. Cases with ≥ 4 (up to ≥ 10) positive nodes were more likely to be concordant (p = 0.009- < 0.001), with improvements of 8.27%-12.37%. For size, cut-offs of ≥ 5 and ≥ 10mm were significant (p = 0.006- < 0.001). It is critical that clinical-radiological-pathological findings be interpreted together with cytology. Aspirates from smaller nodes are more likely to be non-informative, irrespective of the total number of suspicious nodes, or a high-grade primary. In axillae with less than 4 suspicious nodes and/or a target node of less than 5-10mm, the diagnostic accuracy of aspiration cytology decreases and should be interpreted cautiously.

Abstract C042: TMEM doorway score as a predictive biomarker for therapy selection in ER+/HER2- breast cancer

Abstract Background: Endocrine therapy is the standard of care for ER+/HER- breast cancer; but some patients need additional adjuvant chemotherapy to counter the risk of metastasis. While chemotherapy can reduce metastasis, some patients still relapse. Tumor cells metastasize through TMEM (Tumor Microenvironment of Metastasis) Doorways, consisting of a Mena-expressing tumor cell, a macrophage, and a vascular endothelial cell, all in direct contact. High TMEM doorway scores correlate with increased dissemination in mice and metastatic outcomes in ER+/HER2- breast cancer patients. Recent studies show that adjuvant chemotherapy may activate growth in disseminated tumor cells (DTCs). Thus, we hypothesized that patients with high TMEM doorway scores who receive endocrine plus chemotherapy will have worse distant recurrence-free survival (DRFS) than those with lower TMEM Doorway scores, or those who receive endocrine therapy alone. Methods: We conducted a retrospective study on 119 patients with stage I-III, ER+/HER2- unilateral invasive ductal breast carcinoma (age≥18) from 2005- 2018. All underwent surgery and received adjuvant endocrine treatment alone or with chemotherapy. We excluded patients who had metastatic disease at diagnosis, received neoadjuvant chemotherapy, or lacked treatment data. Formalin-fixed paraffin-embedded primary tumor tissues were stained for TMEM doorways. A pathologist categorized the TMEM doorway scores as low, intermediate, or high. Kaplan-Meier curves and Cox-proportional hazard models compared DRFS based on treatment type and TMEM doorway scores. Multivariate logistic regression analyzed the association between macrophage density or TMEM Doorway Score and metastatic outcomes, adjusting for tumor size, grade, and node positivity. Results: Of all patients, 72 received endocrine plus chemotherapy and 47 endocrine therapy alone. In the chemotherapy group, 34 (47.2%) developed metastases, while 38 (52.8%) remained disease-free. In the endocrine alone group, 37 (78.7%) remained disease-free and 9 (19.1%) developed metastases. There was no significant difference in TMEM Doorway Scores between groups (p=0.07). In patients who received endocrine plus chemotherapy, a high TMEM Doorway Score was associated with greater odds of metastasis (OR 6.8; 95% CI 1.35–33.76; p=0.02), controlling for tumor size, grade, and node positivity but not when endocrine therapy was used alone (p=0.817). Patients with high TMEM Doorway Scores had worse DRFS in the endocrine plus chemotherapy group (HR 2.61; 95% CI 1.08–6.27; p=0.03), but not in the endocrine therapy alone group (p=0.77) adjusted similarly. Conclusions: This study highlights potential clinical utility of TMEM Doorway Scores as a predictive biomarker for chemotherapy selection in ER+/HER2- breast cancer patients. Larger trials are needed to confirm these findings and with confirmation, physicians considering giving chemotherapy to ER+/HER2- breast cancer patients might consider pre-treatment stratification using TMEM Doorway Scores to mitigate the risk of chemotherapy-induced metastasis. Citation Format: Priyanka Parmar, Andrew Miller, Burcu Karadal-Ferrena, Suryansh Shukla, Cien Huang, Mindy Ginsberg, Chedva Rosenbaum, Malka Felder, Chenxin Zhang, John S. Condeelis, Xiaonan Xue, Thomas E. Rohan, Joseph A. Sparano, Jesus D. Anampa, David Entenberg, Maja H. Oktay. TMEM doorway score as a predictive biomarker for therapy selection in ER+/HER2- breast cancer [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 C042.

Abstract C040: Spatial transcriptomics unveils disparities in tumor microenvironment dynamics between breast cancer responders and non-responders

Abstract Spatial transcriptomics is revolutionizing our understanding of cellular dynamics and interactions in the tumor microenvironment (TME). By mapping distinct cellular populations and their interactions, we can gain valuable insights into tumor behavior. To investigate these dynamics in breast cancer, we conducted Xenium In-situ spatial transcriptomics on twenty formalin-fixed paraffin-embedded (FFPE) samples taken from eight patients undergoing neoadjuvant chemotherapy. These samples have been taken pre-treatment, mid-treatment and post-treatment from four cases with pathological complete response (pCR), and four cases with residual disease (RD) at time of surgery. Our analyses have found distinct cellular composition changes between pCR and RD cases. Patients with RD demonstrated an increase in endothelial, perivascular-like (PVL) and epithelial cells from pre- to post-treatment. This was accompanied by a decrease in myeloid and malignant epithelial cells at mid-treatment. In contrast, patients with pCR demonstrated increases in cancer-associated fibroblasts (CAFs) and myeloid cells, with reductions in plasmablasts and cancer epithelial cells at mid-treatment. This suggests that an increase in CAF and myeloid cells observed between pre-treatment and mid-treatment samples may be predictive of response. We performed ligand-receptor (LR) analyses, which demonstrated diverse myeloid interactions in RD cases and diverse CAF interactions in pCR cases in pre-treatment samples. Mid-treatment samples exhibited a decrease in interactions for CAFs, myeloid and T cells in pCR and RD cases. The most frequently identified CAF LR interactions, as senders, were between TGFB1/TGFB3 and TGFBR1/TGFBR2, while the most frequently identified myeloid LR interactions were between PDCD1LG2 - PDCD1 (encoding PDL2 &amp; PD1), CCL8 - ACKR1 (encoding Atypical Chemokine Receptor 1) and CCL2 - ACKR1. Our findings indicate that the dynamic changes in cellular composition and interactions within the TME differs between responders and non-responders. To further explore these differences, we plan to perform spatially constrained analyses to identify unique cellular niches that may serve as potential biomarkers for informing novel therapeutic strategies. Citation Format: Jeremy Mo, Hanyun Zhang, Kate Harvey, Alexander Swarbrick. Spatial transcriptomics unveils disparities in tumor microenvironment dynamics between breast cancer responders and non-responders [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 C040.

Exploring the correlation between Tom1L1 and the efficacy of neoadjuvant chemotherapy for locally progressive mid-low rectal cancer.

To investigate the specificity of Target of Myb1-Like1 (Tom1L1) expression in colorectal adenocarcinoma tissues and analyze the predictive value of Tom1L1 in the efficacy of neoadjuvant chemotherapy for patients with rectal adenocarcinoma. The cancerous tissues and paracancerous normal tissues of 102 patients diagnosed with colorectal adenocarcinoma without treatment were selected; quantitative polymerase chain reaction (qPCR), Western blot and immunohistochemistry (IHC) were adopted to validate the expression level of Tom1L1 in the two groups. Furthermore, 34 patients with locally progressive mid-low rectal adenocarcinoma, who were treated with neoadjuvant Xelox chemotherapy prior to the operation, IHC was adopted to detect the expression of Tom1L1 protein in patients before and after neoadjuvant chemotherapy and to analyze the relationship between the expression level of Tom1L1 and the sensitivity of neoadjuvant therapy. The results of qPCR, Western blot and IHC showed that the expression of Tom1L1 in colorectal adenocarcinoma tissues was significantly higher than that in paracancerous normal tissues, with a statistically significant difference (P < 0.01); Neoadjuvant chemotherapy was significantly more effective in patients with low expression of Tom1L1 protein than in those with high expression of Tom1L1 protein, with a statistically significant difference (P < 0.05). Tom1L1 is highly expressed in colorectal adenocarcinoma tissues; neoadjuvant Xelox chemotherapy can have an impact on Tom1L1 expression in progressive rectal cancer; patients with locally progressive mid-low rectal adenocarcinoma who have low Tom1L1 expression are more sensitive to neoadjuvant chemotherapy.

Germline BRCA1/2 status and chemotherapy response score in high-grade serous ovarian cancer.

High-grade serous ovarian cancer (HGSOC) can be treated with platinum-based neoadjuvant chemotherapy (NACT) and delayed primary surgery (DPS). Histopathological response to NACT can be assessed using Böhm's chemotherapy response score (CRS). We investigated whether germline BRCA1/2 (gBRCA1/2) genotype associated with omental CRS phenotype. A retrospective study of patients with newly diagnosed FIGO stage IIIC/IV HGSOC prescribed NACT and tested for gBRCA1/2 pathogenic variants (PVs) between September 2017 and December 2022 at The Christie Hospital. The Cox proportional hazards model evaluated the association between survival and key clinical factors. The chi-square test assessed the association between CRS3 (no/minimal residual tumour) and gBRCA1/2 status. Of 586 eligible patients, 393 underwent DPS and had a CRSreported. Independent prognostic factors by multivariable analysis were gBRCA1/2 status (PV versus wild type [WT]), CRS (3 versus 1 + 2), surgical outcome (complete versus optimal/suboptimal) and first-line poly (ADP-ribose) polymerase-1/2 inhibitor maintenance therapy (yes versus no) (all P < 0.05). There was a non-significant trend for tumours with a gBRCA2 PV having CRS3 versus WT (odds ratio [OR] = 2.13, 95% confidence intervals [CI] 0.95-4.91; P = 0.0647). By contrast, tumours with a gBRCA1 PV were significantly less likely to have CRS3 than WT (OR = 0.35, 95%CI 0.14-0.91; P = 0.0291). Germline BRCA1/2 genotype was not clearly associated with superior omental CRS. Further research is required to understand how HGSOC biology defines CRS.

Role of Neoadjuvant Chemotherapy and Surgery in T1 Triple-negative Breast Cancer Treatment: a Single-center, Retrospective Cohort Study

Role of Neoadjuvant Chemotherapy and Surgery in T1 Triple-negative Breast Cancer Treatment: a Single-center, Retrospective Cohort Study

FATS inhibits the Wnt pathway and induces apoptosis through degradation of MYH9 and enhances sensitivity to paclitaxel in breast cancer.

Breast cancer is one of the most prevalent and diverse malignancies, and, with global cases increasing, the need for biomarkers to inform individual sensitivity to chemotherapeutics has never been greater. Our retrospective clinical analysis predicted that the expression of the fragile site-associated tumor suppressor (FATS) gene was associated with the sensitivity of breast cancer to neoadjuvant chemotherapy with paclitaxel. In vitro experiments subsequently demonstrated that FATS significantly increased the inhibitory effects of paclitaxel on breast cancer cells' migration, growth, and survival. An interaction screen revealed that FATS interacted with MYH9 and promoted its degradation via the ubiquitin-proteasome pathway, thereby downregulating Wnt signaling. By overexpressing FATS and MYH9, we demonstrated that FATS enhanced paclitaxel-induced apoptosis in breast cancer cells by degrading MYH9 to downregulate the Wnt pathway. We also demonstrated in a mouse xenograft model that FATS significantly increased the chemosensitivity of breast cancer cells to paclitaxel in vivo. This study presents a new mechanism by which FATS interacts with MYH9 to suppress the Wnt/β-catenin signaling pathway and induce apoptosis, thus enhancing the sensitivity of breast cancer cells to paclitaxel chemotherapy. The results also propose novel biomarkers for predicting breast cancer sensitivity to neoadjuvant chemotherapy with paclitaxel. Finally, we provide in vivo evidence that the combination of paclitaxel with IWR-1, a novel Wnt pathway inhibitor, synergistically suppresses breast cancer growth, laying the foundation for future trials with this drug combination. These results therefore provide a number of potential solutions for more precise treatment of patients with breast cancer in the future.

Oesophageal cancer.

Oesophageal cancer is the seventh leading cause of cancer mortality worldwide. Two major pathological subtypes exist: oesophageal squamous cell carcinoma and oesophageal adenocarcinoma. Epidemiological studies in the last decade have shown a gradual increase in the incidence of oesophageal adenocarcinoma worldwide. The prognosis of oesophageal cancer has greatly improved due to breakthroughs in screening, surgical procedures, and novel treatment modalities. The success achieved with combined modality therapies, including surgery, chemotherapy, and radiotherapy, to treat locally advanced oesophageal cancer is particularly notable. Immunotherapy has become a crucial treatment for oesophageal cancer, with immune checkpoint inhibitor-based therapies now established as the standard of care in adjuvant and metastatic first-line settings. This Seminar provides an overview of advances in the screening, diagnosis, and treatment of oesophageal squamous cell carcinoma and oesophageal adenocarcinoma, with a particular focus on neoadjuvant therapies for locally advanced oesophageal cancer and immune checkpoint inhibitor-based therapies.

Global metabolomic profiling of tumor tissue and paired serum samples to identify biomarkers for response to neoadjuvant FOLFIRINOX treatment of human pancreatic cancer.

Neoadjuvant chemotherapy (NAT) is increasingly used for the treatment of non-metastatic pancreatic ductal adenocarcinoma (PDAC) and is established as a standard of care for borderline resectable and locally advanced PDAC. However, full exploitation of its clinical benefits is limited by the lack of biomarkers that assess treatment response. To address this unmet need, global metabolomic profiling was performed on tumor tissue and paired serum samples from patients with treatment-naïve (TN; n = 18) and neoadjuvant leucovorin calcium (folinic acid), fluorouracil, irinotecan hydrochloride and oxaliplatin (FOLFIRINOX)-treated (NAT; n = 17) PDAC using liquid chromatography mass spectrometry. Differentially abundant metabolites (DAMs) in TN versus NAT groups were identified and their correlation with various clinical parameters was assessed. Metabolomics profiling identified 40 tissue and five serum DAMs in TN versus NAT PDAC. In general, DAMs associated with amino acid andnucleotide metabolism were lower in NAT compared to TN. Four DAMs-3-hydroxybutyric acid (BHB), 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), glycochenodeoxycholate and citrulline-were common to both tissue and serum and showed a similar pattern of differential abundance in both groups. A strong positive correlation was observed between serum carbohydrate 19-9 antigen (CA 19-9) and tissue carnitines (C12, C18, C18:2) and N8-acetylspermidine. The reduction in CA 19-9 following NAT correlated negatively with serum deoxycholate levels, and the latter correlated positively with survival. This study revealed neoadjuvant-chemotherapy-induced changes in metabolic pathways in PDAC, mainly amino acid and nucleotide metabolism, and these correlated with reduced CA 19-9 following neoadjuvant FOLFIRINOX treatment.

Rectal Cancer and Lateral Lymph Node Staging: Interobserver Agreement and Success in Predicting Locoregional Recurrence

Objectives: To evaluate the agreement among radiologists in the evaluation of rectal cancer staging and restaging (after neoadjuvant therapy) and assess whether locoregional recurrence can be predicted with this information. Materials and Methods: Pre-neoadjuvant and after-neoadjuvant therapy magnetic resonance imaging (MRI) examinations of 239 patients diagnosed with locally advanced rectal cancer were retrospectively reviewed by three radiologists. The agreement between the MRI findings (localization of tumor involvement, tumor coverage pattern, external sphincter involvement, mucin content of the mass and lymph node, changes in the peritoneum, MRI T stage, distance between tumor and MRF, submucosal sign, classification of locoregional lymph node, and EMVI) was discussed at the September 2023 meeting of the Society of Abdominal Radiology (SAR) and the interobserver and histopathological findings were examined. The patients were evaluated according to locoregional rectal cancer and lateral lymph node (LLN) staging, and re-staging was performed using MRI images after neoadjuvant treatment. The ability of the locoregional and LLN staging system to predict locoregional recurrence was evaluated. Results: Among the parameters examined, for the MRI T stage and distance between the tumor and the MRF, a moderate agreement (kappa values: 0.61–0.80) was obtained, while for all other parameters, the interobserver agreement was notably high (kappa values 0.81–1.00). LLNs during the restaging with an OR of 2.1 (95% CI = 0.33–4.87, p = 0.004) and a distance between the tumor and the MRF of less than 1 mm with an OR of 2.1 (95% CI = 1.12–3.94, p = 0.023) affected locoregional recurrence. A multivariable Cox regression test revealed that the restaging of lymph nodes among the relevant parameters had an impact on locoregional recurrence, with an OR of 1.6 (95% CI = 0.32–1.82, p = 0.047). With the LLN staging system, an increase in stage was observed in 37 patients (15.5%), and locoregional recurrence was detected in 33 of them (89.2%) (p &lt; 0.001). Conclusions: LLN staging is not only successful in predicting locoregional recurrence among MRI parameters but is also associated with a very high level of interobserver agreement. The presence of positive LLN in the restaging phase is one of the most valuable MRI parameters for poor prognosis.

Prognostic value of neutrophil-to-lymphocyte ratio in gastric cancer patients undergoing neoadjuvant chemotherapy: A systematic review and meta-analysis

Prognostic value of neutrophil-to-lymphocyte ratio in gastric cancer patients undergoing neoadjuvant chemotherapy: A systematic review and meta-analysis

Trends and Outcomes of Neoadjuvant Chemotherapy for Clinical Stage T1 Pancreatic Cancer.

Neoadjuvant chemotherapy (NC) for early pancreatic ductal adenocarcinoma (PDAC) remains controversial. We investigate the adoption of NC and its impact on survival in clinical T1 (cT1) PDAC. National Cancer Database (2006-2017) was reviewed for cT1 PDAC. Patients receiving NC and surgery were compared with patients undergoing upfront surgery (US). A total of 5886 patients were included. NC use increased from 4.8% in 2006 to 18.8% in 2017. The NC group (n = 618) versus the US group (n = 5268) had: younger age (66 years vs. 68 years), smaller tumor size (2 cm vs. 2.2 cm), more pancreas head tumors (77% vs. 70.6%), lower lymph-vascular invasion (25.9% vs. 40.6%), and less lymph node positivity (43.6% vs. 54.5%), p < 0.001. Factors associated with receipt of NC were: younger age, recent year of diagnosis, and treatment at an academic program. In the NC group versus the US group, median OS was 35.2 months versus 28.3 months, p < 0.001. Factors associated with improved survival included: well differentiated pathology, R0 surgical margins, and receipt of chemotherapy. In cT1 PDAC, chemotherapy is associated with improved survival. In a surgery-first approach, only 59% of patients receive adjuvant chemotherapy. These data suggest consideration of neoadjuvant therapy for early pancreatic cancer.

Systemic chemokine-modulatory regimen combined with neoadjuvant chemotherapy in patients with triple-negative breast cancer

BackgroundHigher cytotoxic T lymphocyte (CTL) numbers in the tumor microenvironment (TME) predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) and positive long-term outcomes in triple-negative breast cancer (TNBC). pCR...

Predictive Value of Neutrophil Extracellular Traps in Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer.

Cisplatin-based chemotherapy is the recommended therapy for muscle-invasive bladder cancer (MIBC). However, the efficacy of MIBC for chemotherapy is only about 40%. Therefore, predictors of therapy response are urgently needed. Neutrophils form neutrophil extracellular traps (NETs), a network structure, and growing evidence indicated that it could be a prognostic and predictive marker in cancer. In MIBC, the predictive role of NETs in chemotherapy resistance is unclear. We used the Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression analyses to develop a NETs-associated signature score (NETs-score) for therapeutic response prediction in the discovery cohort (GSE169455). Then the NETs score-based risk stratification was verified in two validation cohorts (Taber et al.'s cohort, our institutional cohort). In the training cohort, high NETs-score was associated with poor chemotherapy response (AUC = 0.781) and reduced recurrence-free survival (RFS) (hazard ratio [HR] = 2.07, 95% confidence interval [CI]: [1.26-3.40], p = 0.003) in MIBC patients. The NETs-score was also demonstrated to be a predictive factor for the efficacy of neoadjuvant chemotherapy in the validation cohort (AUC = 0.731). The accuracy of the NETs-score was superior to other chemotherapy response predictors such as Ba/Sq expression subtype (AUC = 0.711), BRCA2 mutation (AUC = 0.692) and ERCC2 mutation (AUC = 0.548). Furthermore, in our center cohort, the expression level of H3Cit showed a significant difference between the response and no-response group (p = 0.01). Through immunohistochemical validation, NETs was an independent predictor of MIBC neoadjuvant chemotherapy efficacy as determined by the multivariate logistic regression analysis (OR = 5.94, 95% CI: 1.20-45.50, p = 0.045). Patients with high levels of NETs predicted poor response to neoadjuvant chemotherapy. This study was the first to reveal the correlation between the level of NETs in MIBC and the efficacy of chemotherapy, which may provide a theoretical basis regarding NETs inhibitors.