Primary Tumor Nodes Research Articles

The heterogeneity of breast cancer metastasis: a bioinformatics analysis utilizing single-cell RNA sequencing data.

Breast cancer is a common malignancy in women, and its metastasis is a leading cause of cancer-related deaths. Single-cell RNA sequencing (scRNA-seq) can distinguish the molecular characteristics of metastasis and identify predictor genes for patient prognosis. This article explores gene expression in primary breast cancer tumor tissue against metastatic cells in the lymph node and liver using scRNA-seq. Breast cancer scRNA-seq data from the Gene Expression Omnibus were used. The data were processed using R and the Seurat package. The cells were clustered and identified using Metascape. InferCNV is used to analyze the variation in copy number. Differential expression analysis was conducted for the cancer cells using Seurat and was enriched using Metascape. We identified 18 distinct cell clusters, 6 of which were epithelial. CNV analysis identified significant alterations with duplication of chromosomes 1, 8, and 19. Differential gene analysis resulted in 17 upregulated and 171 downregulated genes for the primary tumor in the primary tumor vs. liver metastasis comparison and 43 upregulated and 4 downregulated genes in the primary tumor in the primary tumor vs lymph node metastasis comparison. Several enriched terms include Ribosome biogenesis, NTP synthesis, Epithelial dedifferentiation, Autophagy, and genes associated with epithelial-to-mesenchymal transitions. No single gene or pathway can clearly explain the mechanisms behind tumor metastasis. Several mechanisms contribute to lymph node and liver metastasis, such as the loss of differentiation, epithelial-to-mesenchymal transition, and autophagy. These findings necessitate further study of metastatic tissue for effective drug development.

Metastatic Adenoid Cystic Carcinoma at the Base of the Tongue and Duplicate Breast Cancer Diagnosed During Restaging.

Adenoid cystic carcinoma (AdCC) is a rare malignant tumor that primarily affects the salivary glands but can also occur in other organs. Low incidence and unpredictable clinical behavior make AdCC one of the most difficult head and neck tumors to treat. We present the case of a 54-year-old woman with AdCC localized at the base of the tongue, following radical surgical and oncological therapy. Due to advances in palliative oncological treatment, there is a more than five-year survival period before the progression of metastatic disease. Considering the rare occurrence of this disease, a literature search was also conducted, and therapy options are discussed. Ensuring a sufficient extent of the surgical procedure is still a challenge, and most specialists agree that subsequent postoperative radiotherapy reduces the risk of local recurrence. The effective dose of radiotherapy to the area of the primary tumor and lymph nodes is not clearly defined. The distinct biological behavior of AdCC results in varying sensitivity to chemotherapy or radiotherapy compared to treatments commonly used for head and neck squamous cell carcinomas. Treatment recommendations for these rarer tumors are based mainly on case reports and small clinical trials. The acquired therapeutic experience can contribute to prolonging the survival period of patients and improving their prognosis and quality of life.

The prognostic role of whole-body volumetric positron emission tomography/computed tomography parameters in treatment naive colorectal cancer patients with liver metastases.

The present study aimed to predict the prognostic role of quantitative 18F-fluorodeoxyglucose PET/computed tomography parameters such as maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) obtained from primary tumor, lymph node metastases, and liver metastasis (LM) in patients with colorectal LM (CLM). The research was designed as a retrospective study and 66 patients with CLM were enrolled between January 2017 and December 2018. Primary tumor SUVmax (PSUVmax), liver SUVmax (LSUVmax), and lymph node SUVmax (LnSUVmax) values obtained from the primary tumor, liver, and lymph nodes were recorded. In addition, total MTV (TMTV) and total TLG (TTLG) values were obtained by summing the values obtained from the primary tumor (PMTV and PTLG), lymph nodes (LnMTV and LnTLG), and liver (LMTV and LTLG). Univariate and multivariate Cox regression analysis was used to measure the effects of prognostic variables on mortality and survival. In univariate Cox regression analysis, PMTV (P = 0.001), LnMTV (P = 0.008), LnTLG (P = 0.008), LnSUVmax (P = 0.047), and TTLG (P = 0.038) were identified as prognostic factors for overall survival. No statistically significant relationship was found between MTV and TLG values of LM and overall survival. In multivariate analysis, PMTV (P = 0.022) was identified as an independent prognostic factor. In conclusion, our study demonstrated that the PMTV value used in evaluating treatment-naive patients diagnosed with CLM is an independent prognostic factor for survival. Our results need to be confirmed with more studies involving more patients.

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

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

Immunohistochemistry for assessing toxicity and mechanism of action of anticancer drugs during preclinical trials. From theory to practice

Aim. To identify the most suitable pathogenetic mechanisms for in-depth study of the antitumor and antimetastatic effects of tested hybrid organotin compounds using the immunohistochemical approach.Materials and Methods. Here, we tested bis(3,5-di-tert-butyl-4-hydroxyphenylthiolate) dimethyltin (laboratory code Me-3), belonging to the class of hybrid organotin compounds, on 30 female C57Bl/6 mice using a universal model of transplantable tumors with spontaneous metastasis (B16 melanoma). 48 hours after tumor cell transplantation, we intraperitoneally administered Me-3 once daily to female C57Bl/6 mice for 10 days at a total dose (TD) of 375 mg/kg. For histological analysis, we used the primary tumor node of B16 melanoma. Immunophenotyping of B16 melanoma tissue samples was carried out using the polyclonal antibodies to transforming growth factor beta 1 (TGFβ-1), vascular endothelial growth factor A (VEGFA), Bcl2-associated X Protein (Bcl-2), cluster of differentiation 34 (CD34).Results. After the exposure to Me-3, we found a reduced immunohistochemical signal to TGF-β1 and Bcl-2 3 in the tumor tissue. Low doses of Me-3 have also impacted angiogenesis.Conclusion. Me-3 has a pro-apoptotic and anti-angiogenetic effects on B16 melanoma cells in C57Bl/6 mice.

Evaluating the reduction of elective radiotherapy fields for de novo metastatic nasopharyngeal carcinoma in the immunotherapy era.

This study evaluates the outcomes of omitting the high- and low-risk clinical tumor volume (CTV1 and CTV2) radiation in de novo metastatic nasopharyngeal carcinoma (dnm-NPC) patients in the immunotherapy era. We retrospectively analyzed 45 consecutive dnm-NPC patients receiving chemotherapy and immunotherapy combined with radiotherapy (CIR) from October 9, 2018 to June 1, 2022. Irradiation was only delivered to the primary tumor and retropharyngeal nodes (GTVnx+rn) and gross cervical lymph nodes (GTVnd). The median follow-up was 45 (range, 15-67) months. There was no recurrence in the omitted elective regions. The 36-month LRRFS, PFS, and OS were 95.4%, 44.6%, and 90.8%, respectively. The main grade 3/4 hematologic toxicities were neutropenia (42.2%), anemia (20.0%), and thrombocytopenia (13.3%). The incidence of acute grade 3/4 dermatitis, mucositis, and xerostomia were 4.4%, 8.9%, and 4.4%, respectively. Omitting CTV1 and CTV2 was well-tolerated and provided favorable clinical outcomes in the era of immunotherapy.

Treatment of Unsuspected T4 Non-Small Cell Lung Cancer With Additional Intrapulmonary Nodules

BackgroundThere is limited consensus on the optimal treatment for patients with non-small cell lung cancer (NSCLC) who are found to have additional intrapulmonary nodules in a different ipsilateral lobe (unsuspected pT4-Add) during surgery. This study compared outcomes of patients with unsuspected pT4-Add NSCLC after resection of the primary site tumor with or without resection of additional nodules. MethodsPatients who underwent surgery for cT1-3 N0-1 M0 NSCLC with unsuspected pT4-Add disease in the National Cancer Database (2010-2015) were included. Overall survival and short-term outcomes were compared between patients who underwent resection of only the primary tumor (“primary site resection”) and those who underwent resection of the primary tumor and additional nodules (“extended resection)” by using Kaplan-Meier analysis and propensity score matching on 10 variables. ResultsOf the 339 patients included in this study, 245 (72.3%) underwent primary site resection and 94 (27.7%) underwent extended resection. In a 2:1 variable ratio propensity score-matched analysis of 83 patients who underwent primary site resection and 42 patients who underwent extended resection, no significant difference was found in 5-year overall survival between the 2 groups. ConclusionsThe results of this national analysis suggest that in the setting of unsuspected pT4-Add NSCLC, proceeding without resection of additional nodules may confer similar overall survival for carefully selected patients with appropriate adjuvant therapy.

1090P High concurrent interferon gamma signature expression in the primary tumor and lymph node metastasis is associated with superior outcome upon neoadjuvant ipilimumab + nivolumab in stage III melanoma

1090P High concurrent interferon gamma signature expression in the primary tumor and lymph node metastasis is associated with superior outcome upon neoadjuvant ipilimumab + nivolumab in stage III melanoma

609. LONG-TERM OUTCOMES OF SALVAGE SURGERY AFTER PROTON BEAM THERAPY FOR ESOPHAGEAL SQUAMOUS CELL CANCER

Abstract Background Proton beam therapy (PBT) for esophageal cancer is a promising option for local control, reducing adverse events. The salvage surgery is sometimes performed for residual or recurrent lesion after PBT, however the long-term outcome has not been known for lack of previous reports. Methods Of 374 patients treated with radical PBT for squamous cell carcinoma of the thoracic esophagus at our institution from 2009 to 2018, we selected cases in which salvage surgery was performed. Salvage surgery was defined as surgical resection of recurrent primary tumor and/or lymph node metastases. The primary outcome was overall survival, and secondary outcomes and postoperative complications were investigated. Results Nineteen patients in whom salvage surgery was performed were included. Median age was 66 (55-80) years, male: female: 16:3, clinical stage at initial presentation was I:II:III = 3:6:10, and median time from PBT to relapse was 23.8 months. Esophagectomy were performed in 12 patients, and lymphadenectomy for recurrent lymph node were performed in 7 patients. During a median observation period of 26.5 months postoperatively, 14 cases were confirmed to have died of primary disease, and the median overall survival from salvage surgery was 38.3 months. 8/14 (57.1%) patients had Grade 3 or higher postoperative complications, and no operative mortality was observed. Conclusion We showed the long and short-term outcome of salvage surgery after PBT for esophageal squamous cell carcinoma. Although the risk of postoperative complications was high, some cases of long-term survival after salvage esophagectomy were observed.

Utility of PET-CT for assessment of response to neo-adjuvant chemotherapy in breast cancer.

12 Background: Response to neo-adjuvant chemotherapy (NACT) is associated with prognosis in non-metastatic breast cancer and can potentially inform further therapeutic options. The aim of this study was to correlate post NACT response on PET CT with pathological response. Methods: All patients who underwent pre- NACT (baseline) and post NACT PET CT imaging with F-18 FDG in a dose of 5-7 MBq/kg body weight with a minimum of 185 MBq given intravenously were retrospectively analyzed. Scan was performed on GE Discovery 710 whole-body PET scan with 128 slice CT. Relevant clinical and imaging related details were extracted from the treatment records. Post NACT PET response (PERCIST criteria) in the primary tumor and nodes was correlated with the pathological response on the post surgical specimen. Analysis was done using Microsoft Excel and SPSS v20 (IBM SPSS). Results: The median age was 49 years (range 30-76 years). 83.1% of patients had node positive disease on baseline PET imaging (not pathologically confirmed). Post chemotherapy PET showed complete metabolic response in the primary tumor and regional nodes in 56.3% and 74% of patients respectively. Two patients had progressive local disease. Pathological complete response rates post surgery in triple negative, Her2 neu positive and ER positive group was 50%, 34% and 12% respectively. The sensitivity, specificity, positive predictive value and negative predictive value is tabulated below. Conclusions: Overall FDG PET CT showed good specificity with limited sensitivity for post NACT response assessment in breast cancer. Our results suggest that post NACT PET CT may have limited utility for clinical decision making and at present its use cannot be recommended outside of a clinical trial.[Table: see text]

The Contribution of 68 Ga-FAPI-04 PET/CT to Staging and Prognosis in Gastric Cancer.

This study aimed to compare the diagnostic capabilities of 18 F-FDG PET/CT and 68 Ga-FAPI-04 PET/CT imaging in staging gastric carcinoma, exploring the impact of 68 Ga-FAPI-04 PET/CT on treatment planning and its prognostic significance. The research included 31 patients undergoing staging for gastric cancer, who received both 18 F-FDG PET/CT and 68 Ga-FAPI-04 PET/CT scans. We compared the SUV max and SUV mean of the primary tumor and lymph nodes, the count of organ metastases, tumor-to-background ratios, and overall staging accuracy. Additionally, the study evaluated radiological progression-free survival and overall survival rates. The 68 Ga-FAPI-04 PET/CT demonstrated superior efficacy in identifying the primary tumor compared with 18 F-FDG PET/CT, particularly in cases of poorly cohesive, signet-ring cell, and mucinous subtypes, with detection rates of 96.7% versus 77.4% ( P = 0.006 and P = 0.008, respectively). Analysis of lymph nodes showed a significantly higher detection of positive nodes with 68 Ga-FAPI-04 ( P = 0.026), although no significant differences were observed in SUV max and tumor-to-background ratio on a patient basis ( P > 0.05). SUV max and tumor-to-background ratios for peritoneal involvement were notably higher with 68 Ga-FAPI-04 PET/CT compared with 18 F-FDG PET/CT ( P = 0.04 for both). No significant differences were found in the detection of organ metastases and disease stage between the 2 imaging modalities ( P > 0.05). Primary tumor uptake did not significantly impact radiological progression-free survival or overall survival in either modality. 68 Ga-FAPI-04 PET/CT imaging surpasses 18 F-FDG PET/CT in detecting the primary tumor, especially in poorly cohesive and signet-ring cell gastric cancer types, and offers improved accuracy in disease staging. This indicates its potential to enhance treatment management and prognostic assessment in gastric cancer patients.

Stereotactic ablative radiotherapy for locally advanced non-small cell lung cancer: A systematic review and meta-analysis

IntroductionTo evaluate the feasibility, efficacy and safety of stereotactic ablative radiotherapy (SABR) to the primary tumor and lymph nodes in patients with locally advanced non-small cell lung cancer (LA-NSCLC) who are ineligible for or refused concomitant chemoradiation. Materials and MethodsIn accordance with the PRISMA and MOOSE guidelines, a systematic review with meta-analysis was conducted. The study included reports that assessed the outcomes of SABR treatment in patients with LA-NSCLC. Studies evaluating SBRT as a boost following primary radiotherapy were excluded. The primary outcomes measured were local control (LC) and overall survival (OS). The secondary endpoint was the incidence of severe toxicity (grades 3–5). A meta-regression analysis was performed to explore the relationship between LC, OS, and severe toxicity. The Biologically Effective Dose (BED) was analyzed as a continuous variable. Statistical significance was defined as a p-value < 0.05. ResultsA total of seven studies (3 prospective and 4 retrospective studies) involving 268 patients (SBRT to primary and lymph nodes) were included in the analysis. The pooled 1-year LC rate was 80 % (95 % CI: 63–94 %), and the factors significantly associated with LC were BEDGy10 (p = 0.005) and neoadjuvant chemotherapy (p = 0.005). The 1-year and 2-year OS rates were 74 % (95 % CI: 58–90 %) and 55 % (95 % CI: 34–76 %), respectively. Meta-regression analysis indicated a linear relationship between OS and LC, with a 0.7 % increase in OS for each 1 % improvement in LC (p = 0.005). The pooled rate of grade 3 acute toxicity was 5 % (95 % CI: 1–10 %), and the rate of grade 5 toxicity was 1.7 % (95 % CI: 0–3 %). ConclusionPromising results (LC and OS) with limited toxicity (feasibility) using SABR in LA-NSCLC warrant further research, emphasizing the need for larger, well-designed trials for further validation of the approach.

Impact of Radiotherapy on Endotracheal Intubation Quality Metrics in Patients with Esophageal Cancer: A Challenge for Advanced Airway Management?

(1) Background: Currently, no data are available in the literature investigating the influence of radiotherapy (RT) on endotracheal intubation success in patients with esophageal cancer. This study aims to evaluate the impact of RT on endotracheal intubation quality metrics in patients with esophageal cancer. (2) Methods: Patients with esophageal cancer who underwent RT followed by surgery between 2012 and 2023 at the University Hospital Heidelberg, Germany, were retrospectively analyzed. (3) Results: Fifty-five patients, predominantly males 65.5% with a mean age of 64 years, were enrolled. Overall, 81.8% of the patients had an ASA class of III, followed by 27.2% ASA II. The mean prescribed cumulative total dose to the primary tumor and lymph node metastasis was 48.2 Gy with a mean single dose of 1.8 Gy. The mean laryngeal total dose was 40.0 Gy. Direct laryngoscopy was performed in 80.0% of cases, followed by 12.1% videolaryngoscopy, and 7.2% required fiberoptic intubation. Overall, 96.4% of patients were successfully intubated on the first attempt. (4) Conclusions: It has been demonstrated that post-RT effects can increase the risk of airway management difficulties and complications. The results of our study did not indicate any evidence of impaired advanced airway management in patients with esophageal cancer who had undergone RT.

FDG PET/CT in Staging and Response Evaluation of Primary Urothelial Carcinoma of the Urethra.

Primary urethral urothelial carcinoma is a rare aggressive tumor with a high propensity for local invasion and regional and distal metastases. We describe the usefulness of FDG PET/CT in management of a patient with primary urethral urothelial carcinoma. FDG PET/CT at initial staging showed FDG-avid primary tumor and lymph node metastasis of the left groin, and mild or no activity of the lung metastases due to small size. FDG PET/CT after 4 cycles of chemotherapy showed progression of the primary tumor and lung metastases, partial response of the left inguinal lymphadenopathy, and multiple new sites of FDG-avid metastases.

Anticancer Effects of Spiperone in C57BL/6 Mice with Emphysema and Lung Carcinoma.

The antitumor and antimetastatic activity of dopamine D2 receptor antagonists spiperone was studied in C57BL/6 mice in a model of combined pathology (emphysema and lung cancer). Emphysema was induced by administration of LPS and cigarette smoke extract. Lung cancer was induced by injection of Lewis lung carcinoma cells into the lung. It has been shown that under conditions of combined lung pathology, spiperone prevents inflammatory infiltration and emphysematous expansion of the lungs and reduces the size of the primary tumor node, the number of metastases, and the area of the lungs affected by metastases. Spiperone reduces the number of cancer stem cells (CSCs) in the lungs and blood of mice with combined pathology. CSCs isolated from the lungs and blood of mice with combined pathology treated with spiperone had a significantly lower potential to form a tumorosphere in vitro than CSCs from untreated mice with emphysema and lung carcinoma. Thus, blockade of dopamine D2 receptors is a promising approach for correcting combined lung pathology and can be used in the development of a method for treating lung cancer in patients with emphysema.

Multi-regional sequencing reveals the genetic and immune heterogeneity of non-cancerous tissues in gastric cancer.

Gastric cancer (GC) is one of the most heterogeneous tumors. However, research on normal tissue adjacent to the tumor (NAT) is very limited. We performed multi-regional omics sequencing on 150 samples to assess the genetic basis and immune microenvironment in NAT and matched primary tumor or lymph node metastases. NATs demonstrated different mutated genes compared with GC, and NAT genomes underwent independent evolution with low variant allele frequency. Mutation profiles were predominated by aging and smoking-associated signatures in NAT instead of signatures associated with genetic instability. Although the immune microenvironment within NATs shows substantial intra-patient heterogeneity, the proportion of shared TCR clones among NATs is five times higher than that of tumor regions. These findings support the notion that subclonal expansion is not pronounced in NATs. We also demonstrated remarkable intra-patient heterogeneity of GCs and revealed heterogeneity of focal amplification of CD274 (encoding PD-L1) that leads to differential expression. Finally, we identified that monoclonal seeding is predominant in GC, which is followed by metastasis-to-metastasis dissemination in individual lymph nodes. These results provide novel insights into GC carcinogenesis. © 2024 The Pathological Society of Great Britain and Ireland.

Differential sensitivities of primary tumor and lymph nodes to induction chemotherapy and definitive radiotherapy in nasopharyngeal carcinoma.

e18037 Background: Risk factors associated with differential sensitivities of primary tumors and lymph nodes to induction chemotherapy and their impact on clinical outcome in nasopharyngeal carcinoma (NPC) patients are undetermined. Methods: During June 2017 to June 2022, 105 NPC patients treated with comprehensive induction chemotherapy and concurrent chemoradiotherapy in our institute were eligible for analysis. Logistic regression analysis was used to identify factors associated with differential sensitivities of primary tumors and lymph nodes to induction chemotherapy (IC). Correlation and regression analysis were used to investigate whether there was a linear relationship between the sensitivity to induction chemotherapy and the efficacy of chemoradiotherapy. COX regression models were used to find prognostic factors, and Kaplan-Meier survival analysis was used to compare prognostic differences among groups with different induction chemotherapy sensitivities. Results: The median patient follow-up time was 26.0 (95%CI: 23.0-34.0) months. Grouped according to the response of the tumor primary site and lymph nodes to induction chemotherapy, we identified potential risk factors associated with different response patterns: primary tumor non-responsive and lymph node non-responsive, performance status (PS) score (OR: 3.824, 95% CI: 1.005-14.558, p = 0.030) ; primary tumor non-responsive but lymph node responsive, hemoglobin level (OR: 1.033, 95% CI: 1-1.067, p = 0.039) ; primary tumor responsive but lymph node non-responsive, N stage (OR: 2.297, 95% CI: 0.103-0.857, p = 0.014), white blood cell count (OR: 1.32, 95% CI: 1.025-1.699, p = 0.030); lymphocyte count (OR: 3.499, 95% CI: 1.196-10.241, p = 0.018) and blood urea nitrogen (OR: 1.416, 95% CI: 1.055-1.901, p = 0.021); primary tumor responsive and lymph node responsive, N stage (OR: 2.02, 95% CI: 1.044-3.907, p = 0.033), red blood cell count (OR: 0.369, 95% CI: 0.157-0.865, p=0.018) and lymphocyte count (OR: 0.359, 95% CI: 0.151-0.856, p = 0.015). Tumor response 6 months after chemoradiotherapy was significantly associated with tumor response after induction chemotherapy (p = 0.037). Similarly, lymph node response 3 months after chemoradiotherapy was significantly associated with lymph node response after induction chemotherapy (p = 0.043). White blood cell count (HR: 1.327, 95% CI: 1.035-1.701, p = 0.026) and neutrophil count (HR: 1.405, 95% CI: 1.049-1.882, p = 0.022) was risk factors associated with progression free survival. Conclusions: In this study, we identified PS score and hemoglobin as potential factors associated with differential sensitivities of primary tumors and lymph nodes to induction chemotherapy in NPC. However, our study found the efficacy of induction chemotherapy could predict the efficacy of chemoradiotherapy or progression free survival.

Pan-tumor harmonization of pathologic response assessment for standardized data collection in neoadjuvant IO trials (PATHdata): Final analysis of a multi-institutional reproducibility study.

2515 Background: Immunotherapeutic agents are now being investigated for treating earlier-stage cancers. Radiographic assessment by RECIST, widely used to assess treatment response in clinical trials for advanced cancers, has limitations in the neoadjuvant setting; and pathologic response assessment is increasingly being used as a primary and/or secondary endpoint. To that end, a pan-tumor scoring system for assessing pathologic response was developed (1,2). This scoring system allows for the quantitative assessment of residual viable tumor (RVT) in multiple locations: i.e. primary and lymph node (LN) or distant metastases, akin to RECIST. %RVT scored using this system been associated with patient outcomes after treatment with anti-PD-1-based therapies. Additionally, %RVT in LN has been shown to have additive value to %RVT in the primary tumor when predicting patient survival (3). As a result, pathologists are now being asked to score pathologic response in the primary tumor and LN as a part of ongoing clinical trials and routine clinical care. Here, we evaluated the reproducibility of %RVT scoring using pan-tumor immune-related pathologic response criteria (irPRC). Methods: A multi-institutional, international study led by the Society for Immunotherapy of Cancer was initiated to assess the concordance of pathologic response assessment in resection specimens from patients treated with anti-PD-1-based therapies. Online lecture-based modules for irPRC scoring were developed, and 14 pathologists from multiple institutions, including academic and industry partners, were trained to score H&amp;E-stained slides. The pathologists have scored n=37 pathology cases from resection specimens and on-treatment biopsies from &gt;10 different tumor types, in part derived from phase II/III clinical trials. %RVT in the primary tumor and LN from patient specimens were scored separately (total of n=374 slides scored by each pathologist). Results: At the first interim analysis, scoring of pathologic response using irPRC was shown to be highly reproducible, irrespective of disease location (i.e. primary tumor vs lymph node metastasis). The second half of the study is nearing completion, and these reproducibility numbers will be finalized and presented in the final abstract. Extended analyses will also be presented that include subset analyses by tumor type. Conclusions: The results will be interpreted and presented in the context of the larger field for pathologic response assessment. A post-study survey completed by the participating pathologists will be used to refine irPRC training materials prior to dissemination to the wider immuno-oncology community. 1. Cottrell et al. Ann Oncol2018. 2. Stein et al. Clin Can Res 2020. 3. Deutsch, et al. Nat Med 2023.

ETHAN: A phase II study comparing different endocrine therapies for male breast cancer.

TPS632 Background: Male breast cancer is a rare disease, and most cases are hormone receptor-positive (HR+). Due to a lack of clinical trials, male breast cancer has historically been treated based on data extrapolated from women. However, there are substantial knowledge gaps in the comparative efficacy, safety, and patient-reported outcomes of endocrine therapies for male breast cancer. While tamoxifen is the current standard of care, additional data are warranted for aromatase inhibitors (AI), gonadal suppression, and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Methods: This is an open-label, multicenter, randomized, phase II trial designed to evaluate different endocrine therapies in men with HR+ and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. A total of 60 men will be enrolled across nine (9) sites within the Translational Breast Cancer Research Consortium (TBCRC). Key eligibility criteria include male sex and stage I, II, or III HR+/HER2- breast cancer before surgical resection of the primary tumor and axillary nodes. Key exclusion criteria include prior anti-cancer therapy for the current breast cancer or any other malignancy within the past 12 months, and inflammatory breast cancer. The trial has two phases. The first phase is a window of opportunity component in which newly diagnosed men are randomized 1:1:1 to either tamoxifen (Arm A), anastrozole (Arm B), or anastrozole plus degarelix (Arm C) given for three weeks. The primary endpoint for the window phase is Ki-67 reduction from the baseline diagnostic biopsy to the research biopsy at the end of the window phase. The second phase consists of neoadjuvant treatment, in which the tamoxifen group is randomized 1:1 to tamoxifen (Arm D) versus tamoxifen plus abemaciclib (Arm E), and the anastrozole alone (Arm B) and anastrozole plus degarelix (Arm C) groups are merged and then randomized 1:1 to anastrozole plus degarelix (Arm F) versus anastrozole plus degarelix plus abemaciclib (Arm G). The duration of the neoadjuvant phase is four (4) months, and the primary endpoint of this phase is residual cancer burden (RCB) index at time of surgery. The trial is powered for the RCB endpoint in a 2 x 2 factorial design to detect a 0.6 unit decrease in RCB index with 80% power and alpha=10%. For the Ki-67 endpoint, we assume an approximately 50% reduction in Arms A and B; Arm C will be of interest if it leads to ≥80% reduction in Ki-67. Secondary endpoints include: estradiol and testosterone levels at baseline, end of window, and during neoadjuvant phase; preoperative endocrine prognostic index (PEPI) score at surgery; adverse events; and patient-reported outcomes (including quality of life). Tumor tissue will be collected for correlative analyses. The study opened to enrollment at Dana-Farber in October 2023, and additional sites will open in 2024. Clinical trial information: NCT05501704 .

Single-cell and spatial transcriptomics reveal metastasis mechanism and microenvironment remodeling of lymph node in osteosarcoma

BackgroundOsteosarcoma (OS) is the most common primary malignant bone tumor and is highly prone to metastasis. OS can metastasize to the lymph node (LN) through the lymphatics, and the metastasis of tumor cells reestablishes the immune landscape of the LN, which is conducive to the growth of tumor cells. However, the mechanism of LN metastasis of osteosarcoma and remodeling of the metastatic lymph node (MLN) microenvironment is not clear.MethodsSingle-cell RNA sequencing of 18 samples from paracancerous, primary tumor, and lymph nodes was performed. Then, new signaling axes closely related to metastasis were identified using bioinformatics, in vitro experiments, and immunohistochemistry. The mechanism of remodeling of the LN microenvironment in tumor cells was investigated by integrating single-cell and spatial transcriptomics.ResultsFrom 18 single-cell sequencing samples, we obtained 117,964 cells. The pseudotime analysis revealed that osteoblast(OB) cells may follow a differentiation path from paracancerous tissue (PC) → primary tumor (PT) → MLN or from PC → PT, during the process of LN metastasis. Next, in combination of bioinformatics, in vitro and in vivo experiments, and immunohistochemistry, we determined that ETS2/IBSP, a new signal axis, might promote LN metastasis. Finally, single-cell and spatial dissection uncovered that OS cells could reshape the microenvironment of LN by interacting with various cell components, such as myeloid, cancer-associated fibroblasts (CAFs), and NK/T cells.ConclusionsCollectively, our research revealed a new molecular mechanism of LN metastasis and clarified how OS cells influenced the LN microenvironment, which might provide new insight for blocking LN metastasis.