Extracapsular Extension Research Articles

Intermediate risk prostate tumors contain lethal subtypes

In 2024, prostate cancer (PCa) remains the most common non-skin cancer in males within the United States, with an estimated 299,010 new cases, the highest increase incident trend rate (3.8%) of all cancers, and one of the eight deadliest. PCa cases are projected to double from 1.8 million to 2.9 million per year between 2020 and 2040. According to the National Comprehensive Cancer Network (NCCN) treatment guidelines, most cases (65%) are intermediate risk (Gleason sum score <7 [3 + 4, 4 + 3], prostate organ-confined, and PSA < 20) with treatment options limited to active surveillance, external beam radiation, and/or surgery to prevent metastasis in the long term (>10 years). It is increasingly recognized that the two most common subtypes of intermediate risk PCa are cribriform architecture (CA) and intraductal carcinoma of the prostate (IDC-P), which can occur together, and both are associated with increased metastatic risk, biochemical recurrence, and disease-specific mortality. Both subtypes display hypoxia, genomic instability, and are identified as Gleason 4 in pathology reports. However, since false negatives are common (up to 50%) in these subtypes on biopsy, more research is needed to reliably detect these subtypes that have an increased risk for invasive disease. We note that even with mpMRI-guided biopsies, the sensitivity is 54% for cribriform architecture and only 37% for IDC-P. The presence of these PCa subtypes in biopsy or radical prostatectomy (RP) tissue can exclude patients from active surveillance and from designation as intermediate risk disease, further underscoring the need for increased molecular understanding of these subtypes for diagnostic purposes. Understanding the heterogeneity of intermediate risk primary PCa phenotypes, using computational pathology approaches to evaluate the fixed biopsy specimen, or video microscopy of the surgical specimen with AI-driven analysis is now achievable. New research associating the resulting phenotypes with the different therapeutic choices and vulnerabilities will likely prevent extracapsular extension, the definition of high-risk disease, and upstaging of the final pathologic stage.

Potential value of Prostate Cancer Antigen 3 score in prediction of final cancer pathology parameters in radical prostatectomy patients.

To evaluate the potential capability of preoperative urinary Prostate Cancer Antigen 3 (PCA3) in predicting adverse pathologic features in patients with any- risk prostate cancer undergoing open retro-pubic radical prostatectomy. Sixty-one biopsy-proven, clinically localized prostate cancer patients who underwent open radical prostatectomy were included in a prospectively designed cohort to evaluate the association of PCA3 score with various Adverse Pathologic Features (APF). The Area Under the Curve (AUC) of the Receiver Operating Characteristics (ROC) curve was used to quantify the predictive accuracy of PCA3 and a cut-off point was calculated to determine the predictability potential of PCA3 in foretelling the study parameters. Patients with APFs (e.g. extra-capsular extension, higher tumor volume, etc.) had a higher mean level of PCA3 compared to patients without these features, with statistically significant differences. PCA3 was a significant predictor of any APFs except perineural invasion in our study cohort. Increasing PCA3 level was associated with any APFs except perineural invasion in our study, which comprised mostly of intermediate and high-risk prostate cancer patients. Therefore, PCA3 could be used as an adjunctive measure in selecting patients for definitive treatments.

Patterns of Recurrence Following Radiation and ADT for Pathologic Lymph Node-Positive Prostate Cancer: A Multi-institutional Study.

We evaluate prognostic factors and patterns of recurrence in patients who received RT ± androgen deprivation therapy (ADT) for pathologic node-positive (pN1) prostate cancer (PCa) in a multi-institutional cohort. Data from patients with pN1 PCa and received RT with short-term (ST, ≤6 mo) or long-term (LT, >6 mo) ADT were obtained from 4 academic institutions. Biochemical progression-free survival (bPFS) and distant metastasis-free survival (DMFS) were evaluated. Two hundred seventy patients were included, with a median follow-up of 48 months. Two hundred fifty-six (95%) patients had extracapsular extension, 70% had seminal vesicle invasion, 59% had positive surgical margins, 49% had grade group 5, and 64% had a detectable (>0.1 ng/mL) postoperative prostate-specific antigen (PSA). ADT was ST (20%) or LT (68%, median 24 months), whereas 26 (10%) received no ADT. Biochemical failure (bF) was observed in 29%, with 5% having pelvic nodal failure and 11% having distant metastases. The 4-year bPFS was 72% overall, and was 83% for a pre-RT PSA of <0.1 ng/mL, 76% for PSA 0.1 to <0.5 ng/mL, 60% for PSA 0.5 to 2 ng/mL, and 35% for PSA > 2 ng/mL (P < .0001). On multivariable analysis, pre-RT PSA > 0.5 (0.5-2.0 vs <0.1 hazard ratio (HR), 2.97; >2.0 vs <0.1 HR, 7.63), use of LT ADT versus no ADT (HR, 0.43) and use of LT ADT compared to ST ADT (HR, 0.34), Grade group 4 versus 2 (HR, 4.11), and positive surgical margins (HR, 1.773) were significantly associated with bPFS. Postprostatectomy RT at PSA < 0.5 ng/mL is associated with favorable bPFS in pN1 PCa.

Tumor budding and lymphovascular invasion as prognostic factors in p16-positive oropharyngeal squamous cell carcinomas

BackgroundWe aimed to validate the prognostic significance of tumor budding (TB) in p16-positive oropharyngeal squamous cell carcinomas (OPSCC).MethodsWe analyzed digitized H&E-stained slides from a multicenter cohort of five large university centers consisting of n = 275 cases of p16-positive OPSCC. We evaluated TB along with other histological parameters (morphology, tumor-stroma-ratio, lymphovascular invasion (LVI), perineural invasion) and calculated survival outcomes using both univariate and multivariate analyses.ResultsTB was identified as an independent prognostic parameter, with TB-high cases showing inferior outcomes in univariate (HR: 3.08, 95%-CI: 1.71–5.54) and multivariate analyses (HR: 4.03, 95%-CI: 1.65–9.83). Similarly, LVI remained an independent prognostic factor (HR: 3.00, 95%-CI: 1.22–7.38). A combined classification including TB and LVI stratified cases into low-, intermediate- and high-risk categories. We could not detect correlations between TB and the number of lymph node metastases or between TB and an extracapsular extension of lymph node metastases.ConclusionsIn addition to LVI, we could identify TB as an independent prognostic factor in p16-positive OPSCC in this multicenter study cohort. Thus, evaluating TB along with LVI in a combined scheme for prognostication might help to establish a more personalized treatment regimen for patients with p16-positive OPSCC.

Abstract A055: Tumor muscle invasion promotes tumor heterogeneity and normal muscle reprogramming

Abstract Aggressive human prostate tumors traverse a contractile smooth muscle pseudo-capsule, in a process termed extracapsular extension (ECE), defining the pT3 pathologic stage associating with increased biochemical recurrence, bone metastases, and cancer-specific mortality. While T3 lesions can be detected by non-invasive mpMRI imaging, how the tumor invades into and through the contractile muscle is unknown. Using a mouse xenograft model system of ECE, we investigated the transcriptomic consequences of human tumor invasion into and through the contractile smooth muscle of the mouse diaphragm. Both human and mouse gene transcripts were documented and analyzed. Tumor cells were intraperitoneally injected into male NSG mice and 6 weeks later, three tumor compartments (pre-invasive, muscle-invasive, and super-invasive cells that had reached the superior diaphragm surface) were analyzed for differential bulk human and mouse gene expression. Whole genome transcriptomic sequencing and GO pathway analysis revealed that approximately 414 human genes were differentially expressed between the non- invasive, muscle-resident, and super-invasive tumor populations and at least 5 enriched pathways were involved. The unique expression gene patterns of muscle-resident tumor cells were reversible when compared to the pre-invasive and super-invasive expression patterns. Significant increases in g-H2AX and nuclear deformation were observed in the muscle-resident tumor clusters as compared to the non-invasive tumor mass. No differences in tumor cell proliferation, as detected by Ki67 staining, were found between the tumor clusters in the three compartments. Immunohistochemistry staining for a damage response cytokeratin (KRT6A) and integrin (CD49f) revealed heterogeneity within the muscle resident tumors as compared to the non- invasive cells. Taken together, these data suggest a hostile contractile muscle environment elicits specific responses by the invading tumor. Single cell analysis within each of the tumor compartments is currently underway to define the spatial heterogeneity of gene expression in invasive tumor cell clusters within the contractile muscle. A dynamic reciprocity of the tumor/muscle microenvironment is suggested by the analysis of the bulk transcriptomic sequencing demonstrating a significant increase in mouse muscle bio-synthetic gene transcription as a consequence of the human tumor penetrating the tissue. Taken together, these data indicate that human tumors, during the act of traversing the contractile muscle layer, respond to this unique microenvironment by transiently altering transcription, while sustaining nuclear damage which results in the reprogramming of the muscle. This new information suggests that novel tumor or muscle biomarkers might indicate early muscle invasion events and assist new high-resolution image analysis for precision diagnostic and/or therapeutic decisions. (Supported in part by P30 CA23074; F30 CA143924, UACC Team Science Award). Citation Format: Kendra D Marr, Beatrice S Knudsen, Rafael Sainz, Kelvin W Pond, Noel E Warfel, Belinda E Sun, Anne E Cress. Tumor muscle invasion promotes tumor heterogeneity and normal muscle reprogramming [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A055.

Abstract B031: Immune cell composition in surgical drain fluid as a novel prognostic marker in head and neck squamous cell carcinoma

Abstract Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy globally, and the vast majority of cases are treated with primary surgical resection and adjuvant therapy. Our group has pioneered the use of HNSCC circulating tumor DNA (ctDNA) in surgical effluent collected postoperatively from surgical drains (surgical drain fluid, SDF) as a novel proximal bioanalyte for measuring minimal residual disease after surgery. We now profile the immune cell composition of SDF compared to paired peripheral blood mononuclear cells (PBMCs), and correlate SDF immune cell profiles with clinical variables and oncologic outcomes in HNSCC. Method: SDF and peripheral venous blood were collected 24 hours postoperatively from 58 HNSCC patients, including 11 HPV (+) and 47 HPV (-) patients undergoing standard of care surgical resection, lymph node dissection, and adjuvant therapy. Freshly collected SDF cells and PBMCs were cryopreserved until profiling by multicolor flow cytometry for respective leukocyte compositions. Analyses were used to define the following viable CD45+ leukocyte subsets: total T cells, CD4 T-cells CD8 T-cells, Treg cells, B-cells, non- classical monocytes, classical monocytes, natural killer (NK) cells, classical dendritic cells (cDC), plasmacytoid DC (pDC), macrophages, and monocytic myeloid-derived suppressive cells (MDSCs). Immune cell percentages were correlated with clinical characteristics and cancer recurrence. Results: CD45+ leukocytes comprised &amp;gt;99.5% of SDF cells, with very few EPCAM+ tumor cells (&amp;lt; 10^-4). HPV status did not significantly affect SDF immune cell composition, and no significant differences were noted by tumor site (larynx, oral cavity, oropharynx), or extracapsular lymph node extension. Among 13 HPV (-) HNSCC patients with paired peripheral blood drawn concurrently, SDF had a higher proportion of B-cells(16.8% vs. 9%, p=0.044), NK cells(56% vs. 12%, P&amp;lt;0.001), monocytes(14% vs. 1%, P&amp;lt;0.001), and macrophages(3.1% vs. 0.46%, P&amp;lt;0.001) compared to PBMCs, and a lower proportion of CD4+ T cells(1% vs. 24%, P&amp;lt;0.001), CD8+ T cells(0.6% vs. 18%, P&amp;lt;0.001), MDSCs(2.1% vs. 3.4%, P=0.029), and pDCs(0.1% vs. 0.2%, P=0.014). HPV (-) HNSCC patients that went on to recur (n=9) had a significantly higher proportions of SDF monocytes (total, classical, and non- classical) and CD56dimCD16+ NK cells (all P&amp;lt;0.001) compared to non-recurrent patients (n=38). Patients who went on to recur also had a significantly lower proportion of SDF B-cells (P&amp;lt;0.001), CD56bright NK cells(P=0.01), and macrophages (P=0.018) compared to non- recurrent cases. No significant differences were noted with respect to proportions of CD3+, CD4+, CD8+ T-cells, DC, and MDSC cells. Conclusion: SDF from HNSCC patients contains unique immune cell populations and may provide new insights into postoperative tumor immunity. Differences in SDF immune cell composition by oncologic outcome in patients that go on to recur, highlighting potential prognostic and predictive applications of SDF immune cell profiling for adjuvant therapy decision-making. Citation Format: Zhongping Xu, Noah Earland, Lucien Khalil, Lazar Vujanovic, Danny Azmi Elias, Riyue Bao, Jason J. Luke, Aadel A. Chaudhuri, Jose P. Zevallos. Immune cell composition in surgical drain fluid as a novel prognostic marker in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B031.

Correlation of Histopathological Characteristics of Nodal Metastasis with Clinicopathologica Features and Survival in Breast Cancer Patients

Background: Involvement of lymph nodes is a significant predictive marker in breast cancer, impacting both patient results and therapy strategies. It is crucial to comprehend the pathological alterations in lymph nodes that are linked to breast carcinoma in order to maximize care for patients.Objective: This study aimed to examine histopathological changes in lymph nodes related to breast cancer and their clinical implications.Materials and Methods: A retrospective observational analysis was conducted from the time duration of 21st November 2022 to 24th April 2023 involving 100 diagnosed breast cancer patients who underwent lymph node dissection. Patient data, including demographics, clinical history, five-year survival rates, and histopathological findings, were collected from medical records. Descriptive statistics and multivariate analysis were used to analyze the data.Results: In a study of breast cancer patients, 60% had macrometastases and 45% had extracapsular extension, indicating aggressive disease. Micrometastases were observed in 30%. Patients with lymph node metastases had poorer outcomes, with lower 5-year survival rates (60%) and higher recurrence rates (35%) compared to those without lymph node involvement (85% and 15%, respectively). Multivariate analysis showed lymph node involvement as a key prognostic factor (hazard ratio 2.5), while larger tumor size and higher histological grade also predicted worse outcomes. Subgroup analysis revealed that isolated tumor cells had the highest 5-year survival rate (75%), while micrometastases and macrometastases had lower rates of 65% and 55%, respectively.Conclusion: The presence of histopathological alterations in the lymph nodes associated to breast cancer is important for predicting outcomes and treatment plans. The number of affected lymph nodes can determine the survival rates of patients, which underlines the importance of proper lymph node assessment for breast cancer treatment.Keywords: Breast cancer, Histopathology, Lymph node involvement, Prognosis, Treatment.

Determining optimal clinical target volume margins based on microscopic extracapsular extension of metastatic nodes in patients with non-small-cell lung cancer after chemotherapy or chemotherapy combined with immunotherapy

BackgroundNo standard has been established for the clinical target volume (CTV) margins of lymph nodes (LNs) in patients with non-small-cell lung cancer (NSCLC) receiving chemotherapy or chemotherapy combined with immunotherapy followed by radiotherapy. This study aimed to discuss the CTV range of NSCLC after chemotherapy or chemotherapy combined with immunotherapy by observing the microscopic extent of tumor spread beyond the LN capsule.MethodsWe retrospectively analyzed the data of 240 patients with stage II and III NSCLC who underwent surgery without neoadjuvant therapy, with neoadjuvant chemotherapy (NAC), or with NAC combined with immunotherapy (NACI). We measured the maximal distance of extracapsular extension (ECE) using a digital microscope, analyzed the correlation between clinicopathological features and ECE distance, and determined the CTV margins of metastatic LN under different treatment methods.ResultsThe ECE distance differed significantly among the three groups (p < 0.001). We determined appropriate margin widths based on a 5% error risk as 3.00, 2.30, and 1.40 mm for direct surgery, NAC, and NACI, respectively. Multivariate analysis revealed that the ECE of metastatic LN correlated with the treatment methods and LN size.ConclusionThe existing CTV delineation standards may increase the radiation toxicity of patients. We believe that different CTV margins should be used for LN in patients with NSCLC receiving different treatments. To ensure 95% coverage of ECE, the gross tumor volume of untreated, chemotherapy-treated, and chemotherapy combined with immunotherapy-treated patients should be expanded by 3.00, 2.30, and 1.40 mm, respectively, to obtain the CTV.

Diagnostic value of the flare sign in predicting extracapsular extension in metastatic axillary lymph nodes and nodal status on breast magnetic resonance imaging.

This study aimed to evaluate the diagnostic performance of breast magnetic resonance imaging (MRI) in predicting extracapsular extension (ECE) and axillary nodal status in the axillary metastatic lymph nodes of patients with breast cancer. The preoperative MRI scans of 92 patients with breast cancer and axillary metastases who did not receive neoadjuvant treatment between January 2018 and January 2024 were retrospectively examined. The presence of an increased signal in the axillary fatty tissue surrounding the lymph node (flare sign) on T2-weighted images, irregular nodal contour (shaggy margin), axillary asymmetry (difference in the number and size of lymph nodes compared with the unaffected axilla), loss of the fatty hilum in the most suspicious lymph node, and morphological features on T1-weighted images were assessed. Each dissected axillary lymph node was examined for ECE, and the histopathological results were recorded. Axillary flare sign was significantly associated with the presence of ECE (P < 0.001), number of lymph nodes with ECE (P < 0.001), the presence of ≥4 axillary metastatic lymph nodes (P < 0.001), size of the primary tumor (P = 0.033), lymphovascular invasion in the primary tumor (P < 0.001), and presence of perineural invasion (P = 0.001). The flare sign exhibited 65.7% sensitivity, 96% specificity, 97.8% positive predictive value, 51.1% negative predictive value, and 73.9% accuracy in predicting ECE. Additionally, the receiver operating characteristic curve analysis revealed an area under the curve of 0.808 (95% confidence interval: 0.719-0.898). The flare sign has high performance in predicting ECE and axillary nodal status and is associated with primary tumor aggressiveness, indicating its potential utility in preoperative evaluation. The flare sign on breast MRI may play a crucial role in preoperative planning, surgical decision-making, and axillary status assessment by accurately predicting ECE.

Machine learning and explainable artificial intelligence to predict pathologic stage in men with localized prostate cancer.

Though several nomograms exist, machine learning (ML) approaches might improve prediction of pathologic stage in patients with prostate cancer. To develop ML models to predict pathologic stage that outperform existing nomograms that use readily available clinicopathologic variables. Patients with prostate adenocarcinoma who underwent surgery were identified in the National Cancer Database. Seven ML models were trained to predict organ-confined (OC) disease, extracapsular extension, seminal vesicle invasion (SVI), and lymph node involvement (LNI). Model performance was measured using area under the curve (AUC) on a holdout testing data set. Clinical utility was evaluated using decision curve analysis (DCA). Performance metrics were confirmed on an external validation data set. The ML-based extreme gradient boosted trees model achieved the best performance with an AUC of 0.744, 0.749, 0.816, 0.811 for the OC, ECE, SVI, and LNI models, respectively. The MSK nomograms achieved an AUC of 0.708, 0.742, 0.806, 0.802 for the OC, ECE, SVI, and LNI models, respectively. These models also performed the best on DCA. Findings were consistent on both a holdout internal validation data set as well as an external validation data set. Our ML models better predicted pathologic stage relative to existing nomograms at predicting pathologic stage. Accurate prediction of pathologic stage can help oncologists and patients determine optimal definitive treatment options for patients with prostate cancer.

Are Clinically Node-Negative Patients with a Positive Preoperative Axillary Lymph Node Biopsy Appropriate Candidates for Sentinel Lymph Node Biopsy?

Whether cN0 patients with image-detected nodal metastases are appropriate for sentinel lymph node biopsy (SLNB) or should proceed directly to axillary lymph node dissection (ALND) or neoadjuvant chemotherapy (NAC) is controversial. We sought to determine how often ALND is needed with upfront surgery and to identify factors associated with ≥ 3 positive SLNs after a positive preoperative lymph node (LN) biopsy. Patients with cT1-2N0 breast cancer and a positive LN biopsy treated from 2014 to 2022 were identified from a prospective database. Patients who received NAC were excluded. Clinicopathologic characteristics were compared between women with 1-2 positive SLNs and ≥ 3 positive SLNs. Of 90 eligible patients, 66 (73%) had 1-2 positive SLNs and 24 (27%) had ≥ 3 positive SLNs. The median patient age was 62 years, median tumor size was 2.2 cm, and 16 women (18%) received a mastectomy. There was no difference in body mass index, tumor size, histology, grade, multifocality, presence of lymphovascular invasion, and receptor status between groups. On multivariable analysis, having ≥ 3 positive SLNs was associated with > 1 abnormal LN on preoperative imaging (odds ratio [OR] 4.36, 95% confidence interval [CI] 1.47-14.0; p = 0.01), microscopic extracapsular extension in the SLNs (OR 3.83, 95% CI 1.25-13.7; p = 0.025), and a higher median number of SLNs removed (OR 1.42, 95% CI 1.10-1.88; p = 0.01). More than 70% of women with cT1-2 breast cancer with image-detected nodal metastases had < 3 positive SLNs and did not require ALND. To avoid multiple trips to the operating room, frozen section can be considered in women with multiple abnormal LNs on imaging.

Five-year Oncologic Outcomes Following Primary Partial Gland Cryo-ablation Prospective Cohort Study of Men With Intermediate-risk Prostate Cancer

To assess 5-year oncologic outcomes following primary partial gland cryo-ablation (PPGCA) in intermediate risk prostate cancer. Of 476 men undergoing PPGCA enrolled in our prospective oncologic and functional outcomes study, 313 had MRI concordant intermediate risk prostate cancer with no out-of-field Gleason Grade Group (GGG) ≥2, gross extracapsular extension or extreme apical disease on pre-treatment mpMRI. PSA was monitored every 6 months, and mpMRI at 6-12, 24, 42 and 60 months. Protocol biopsy at 6-12 months and 24 months were discontinued after interim analysis showing low rates of clinically-significant prostate cancer (csPCa) defined as any GGG≥2 disease. Freedom-from-failure (FFF) was defined as no prostate cancer specific mortality, metastatic disease, or whole-gland salvage treatment (WGST) RESULTS: csPCa was detected in 33 (10.5%) subjects. 91 had ≥4.5 years of follow-up data with a mean of 8.9, 3.4, and 2.0 surveillance PSA tests, MRIs, and prostate biopsies; none were lost to follow-up. At 5-years, rates of freedom-from-recurrence of in-field, out-of-field and overall csPCa were 86% (95% CI: 78-96), 85% (95% CI: 63-94), and 70% (95% CI: 57-84). The proportion with freedom-from-failure (FFF) at 5 years was 89% (95% CI: 83-95). None died from prostate cancer, 1 (1%) developed metastasis, 15 (16.5%) underwent WGST, and 15 (16.5%) underwent salvage focal therapy (FT). Only 3 of 91 (3.3%) eligible men were noncompliant with 5-year surveillance protocol. Very encouraging intermediate-term oncological outcomes following PPGCA were observed with very high compliance to a rigorous prospective protocol for identifying recurrent csPCa.

Survival Outcomes of Total Laryngectomy: Evaluating the Intersection of Race and Social Determinants.

Analyze joint effects of race and social determinants on survival outcomes for patients undergoing total laryngectomy for advanced or recurrent laryngeal cancer at a tertiary care institute. Retrospective chart review of adult patients undergoing total laryngectomy for laryngeal cancer at a tertiary care center from 2013 to 2020. Extracted data included demographics, pathological staging and features, treatment modalities, and outcomes such as recurrence, fistula formation, and 2- and 5-year disease-free survival (DFS) and overall survival (OS). Area Deprivation Index (ADI) was calculated for each patient. Among 185 patients identified, 113 were Black (61.1%) and 69 were White (37.3%). No significant differences were observed between racial groups regarding age, gender, ADI, or cancer stage. There was no significant difference in 2-year DFS/OS between groups. ADI was comparable between racial groups, with the majority in the highest deprivation quintile (63.8% of Whites vs. 62.5% of Blacks). No significant differences were observed in gender, race, cancer stage, positive margins, extracapsular extension, or smoking status among ADI quintiles. We observed a significant difference in 2-year DFS stratified by ADI (p = 0.025). Stratifying by ADI and race revealed improved survival of White patients in lower quintiles but higher survival of Black patients in the highest disparity quintile (p = 0.013). Overall, survival outcomes by race were comparable among laryngectomy patients, but there was a significant difference in 2-year DFS when stratified by ADI. Further research into survival outcomes related to social determinants is needed to better delineate their effects on head and neck cancer outcomes. 3 Laryngoscope, 2024.

Periprostatic adipose tissue inhibits tumor progression by secreting apoptotic factors: A natural barrier induced by the immune response during the early stages of prostate cancer.

Prostate cancer (PCa) is the second most prevalent malignancy in men worldwide. The risk factors for PCa include obesity, age and family history. Increased visceral fat has been associated with high PCa risk, which has prompted previous researchers to investigate the influence of body composition and fat distribution on PCa prognosis. However, there is a lack of studies focusing on the mechanisms and interactions between periprostatic adipose tissue (PPAT) and PCa cells. The present study investigated the association between the composition of pelvic adipose tissue and PCa aggressiveness to understand the role played by this tissue in PCa progression. Moreover, PPAT-conditioned medium (CM) was prepared to assess the influence of the PPAT secretome on the pathophysiology of PCa. The present study included 50 patients with localized PCa who received robot-assisted radical prostatectomy. Medical records were collected, magnetic resonance imaging scans were analyzed and body compositions were calculated to identify the associations between adipose tissue volume and clinical PCa aggressiveness. In addition, CM was prepared from PPAT and perivesical adipose tissue (PVAT) collected from 25 patients during surgery, and its effects on the PCa cell lines C4-2 and LNCaP, and the prostate epithelial cell line PZ-HPV-7, were investigated using a cell proliferation assay and RNA sequencing (RNA-seq). The results revealed that the initial prostate-specific antigen level was significantly correlated with pelvic and periprostatic adipose tissue volumes. In addition, PPAT volume was significantly higher in patients with extracapsular tumor extension. PCa cell proliferation was significantly reduced when the cells were cultured in PPAT-CM compared with when they were cultured in control- and PVAT-CM. RNA-seq revealed that immune responses, and the cell death and apoptosis pathways were enriched in PPAT-CM-cultured cells indicating that the cytokines or other factors secreted from PPAT-CM induced PCa cell apoptosis. These findings revealed that the PPAT secretome may inhibit PCa cell proliferation by activating immune responses and promoting cancer cell apoptosis. This mechanism may act as a first-line defense during the early stages of PCa.

External validation of the PRECE nomogram model in a Central America cohort

Introduction: This is an external validation study of the PRECE prostate cancer nomogram in a Central American population. Methods: We present 102 consecutive cases of robotic radical prostatectomy, performed with preservation of the anterior fascia and we use the PRECE nomogram as a guide to preserve the prostatic neurovascular pedicles. We compared the predicted extra-capsular extension from the PRECE nomogram to the final prostatectomy pathology. Results: Analysis of post-prostatectomy pathological samples revealed that 61% patients had pT2; 27% had a pT3a and 12% had a pT3b, respectively The ROC curve for the PRECE nomogram at one (1) mm showed a model AUC of 0.91 (95% CI), which implies a high agreement with the PRECE nomogram in the prediction of extraprostatic disease. Conclusion: This is the first report of external validation of the PRECE nomogram in a Central American population. PRECE demonstrated high discrimination for the prediction of extraprostatic disease in an independent Latin American cohort. More external validation studies, from different geographic settings, are expected to confirm the reliability and reproducibility of PRECE in other clinical settings.

Prediction of High Nodal Burden in Patients With Sentinel Node–Positive Luminal ERBB2-Negative Breast Cancer

In patients with clinically node-negative (cN0) breast cancer and 1 or 2 sentinel lymph node (SLN) macrometastases, omitting completion axillary lymph node dissection (CALND) is standard. High nodal burden (≥4 axillary nodal metastases) is an indication for intensified treatment in luminal breast cancer; hence, abstaining from CALND may result in undertreatment. To develop a prediction model for high nodal burden in luminal ERBB2-negative breast cancer (all histologic types and lobular breast cancer separately) without CALND. The prospective Sentinel Node Biopsy in Breast Cancer: Omission of Axillary Clearance After Macrometastases (SENOMAC) trial randomized patients 1:1 to CALND or its omission from January 2015 to December 2021 among adult patients with cN0 T1-T3 breast cancer and 1 or 2 SLN macrometastases across 5 European countries. The cohort was randomly split into training (80%) and test (20%) sets, with equal proportions of high nodal burden. Prediction models were developed by multivariable logistic regression in the complete luminal ERBB2-negative cohort and a lobular breast cancer subgroup. Nomograms were constructed. The present diagnostic/prognostic study presents the results of a prespecified secondary analysis of the SENOMAC trial. Herein, only patients with luminal ERBB2-negative tumors assigned to CALND were selected. Data analysis for this article took place from June 2023 to April 2024. Predictors of high nodal burden. High nodal burden was defined as ≥4 axillary nodal metastases. The luminal prediction model was evaluated regarding discrimination and calibration. Of 1010 patients (median [range] age, 61 [34-90] years; 1006 [99.6%] female and 4 [0.4%] male), 138 (13.7%) had a high nodal burden and 212 (21.0%) had lobular breast cancer. The model in the training set (n = 804) included number of SLN macrometastases, presence of SLN micrometastases, SLN ratio, presence of SLN extracapsular extension, and tumor size (not included in lobular subgroup). Upon validation in the test set (n = 201), the area under the receiver operating characteristic curve (AUC) was 0.74 (95% CI, 0.62-0.85) and the calibration was satisfactory. At a sensitivity threshold of ≥80%, all but 5 low-risk patients were correctly classified corresponding to a negative predictive value of 94%. The prediction model for the lobular subgroup reached an AUC of 0.74 (95% CI, 0.66-0.83). The predictive models and nomograms may facilitate systemic treatment decisions without exposing patients to the risk of arm morbidity due to CALND. External validation is needed. ClinicalTrials.gov Identifier: NCT02240472.

Unilateral Neck Treatment with either Surgery and/or Radiotherapy for Squamous Cell Carcinoma for the Tonsil

Introduction: Strategies for treatment of tonsil carcinoma are under active investigation. Limiting surgical and radiation treatment volumes to the primary tumor and ipsilateral neck in appropriately selected patients are one such approach. Here, we present our institutional experience with treatment through ipsilateral surgical or radiotherapeutic neck management. Methods: We retrospectively reviewed our institutional database of patients with tonsil carcinoma treated from 2012 to 2020. Patients were included for analysis if they received definitive radiation therapy (RT), definitive surgery (S), or surgery with postoperative radiation therapy (S-PORT) and whose treatment volumes were limited to the primary tumor and involved/elective ipsilateral neck. Patients who received radiation and/or surgery to the contralateral neck (including those with bilateral nodal involvement), as well as patients with metastatic disease, were excluded. Clinical factors including T- and N-stage (AJCC 7th edition), and HPV status (by p16 and/or HPV DNA PCR) were recorded, as were pathologic factors (when applicable) including margin status, extracapsular extension (ECE), lymphovascular invasion (LVSI), and perineural invasion (PNI). Overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) at 2 years were estimated using the Kaplan-Meier method. Results: In total, 71 patients were treated with unilateral neck approaches: S (n = 49), RT (n = 10), and S+PORT (n = 12). Among these patients, 32, 36, and 3 had T1, T2, and T3 disease, respectively. N-stage was N0, N1, N2a, N2b, and N3 in 22, 20, 5, 23, and 1 patient(s), respectively. Concurrent chemotherapy was administered in 12 patients. From those with recorded risk factors, 86% were HPV positive, 20% had LVSI, 7% had PNI, 13% had ECE, and 5% had positive margins. From a median follow-up of 27 months, local, regional, and distant failures occurred in 5, 6, and 5 patients, respectively. No contralateral neck failures were recorded. At 2 years, OS, PFS, and LRC were 92% (95% CI 85–99%), 85% (95% CI 75–95%), and 88% (95% CI 80–98%), respectively. Conclusions: In patients with early T-stage tonsil carcinoma, treatment of the primary tumor and ipsilateral neck is associated with acceptable OS, PFS, and LRC. In this population, the risk of contralateral neck failure is likely very low regardless of primary treatment modality. Additional prospective studies are needed to determine the impact of limiting treatment extent, either surgical or radiotherapeutic, to the unilateral neck.

Treatment Outcomes and Patterns of Disease Recurrence of Patients with Carcinoma of the Buccal Mucosa.

Locally advanced buccal mucosa cancer is typically treated with surgery and adjuvant postoperative radiation therapy, which includes concurrent Cisplatin 100mg/m2 on Day 1, plus 5-Fluorouracil 1000mg/m2 from Day 1 to 4 every three weeks. Ipsilateral face radiotherapy is a de-escalated treatment that spares the opposite side of the face, enhancing post-treatment chewing function. The availability of electron beam radiotherapy for treating recurrences on the opposite side has increased the use of ipsilateral face radiotherapy. This retrospective study aimed to assess treatment outcomes and patterns of disease recurrence in patients with carcinoma of the buccal mucosa treated with different schedules. We retrospectively reviewed records of 54 patients with a pathological diagnosis of buccal mucosa cancers treated between 2018 and 2023. We extracted patients' demographic, disease, and treatment criteria. Indications for postoperative radiotherapy included a close margin of less than 3mm and lymph node positivity. The primary tumor (face) and neck were considered separately for radiotherapy treatment. One patient who refused surgery, radiotherapy, and chemotherapy but regularly came for follow-up after receiving Ayurvedic treatment died of the disease after 2 years and 1 month. Fifty-three patients received concurrent chemoradiotherapy with Cisplatin 100mg/m2 on Day 1, plus 5-Fluorouracil 1000mg/m2 from Day 1 to 4 every three weeks for three cycles. Postoperative patients were treated with radiotherapy fields covering the face (bilateral or ipsilateral wedged fields) and the whole neck field with central shielding for the initial 44Gy in 22 fractions over 4.5 weeks followed by a boost dose of 16Gy to the primary tumor and involved neck. For radical radiotherapy, patients received a similar radiation field but the boost dose delivered was 26Gy in 13 fractions over 2.5 weeks. For ipsilateral radiotherapy fields, the average face anterior field size was 6W x 8cm; the thick edge of the wedge laterally; depth 4cm and lateral 8W x 8cm radiation field with a thick edge of the wedge anteriorly; depth 3cm. The median dose to high-risk clinical target volume was 60Gy/30 fractions in postoperative cases. Forty-eight patients received radical radiotherapy with a higher dose (66Gy/33 fractions to 70Gy/35 fractions); twenty-eight patients received radiotherapy fields of bilateral face and neck with a central spinal shield of 2cm. Statistical analysis was conducted at the Community Medicine Department using SPSS software version 21.0. The Chi-square test and Fisher Exact test were applied to compare various groups. Fifty-four patients were analyzed. The median follow-up was 9 months. Surgery consisted of Composite Resection (Commando operation) plus Radical Neck dissection in three (5.5%) patients and non-composite resection surgeries (Wide excision of the lesion plus supra-omohyoid dissection) in nine (16.6%) cases, of which six (50%) cases had lymph node involvement but no patient with positive dissection had extracapsular extension. Tumor thickness by histopathology was found to be between 5 and 15mm. Sixteen (28.1%) patients failed locally and 11 (20.3%) had lymph node recurrences. One patient (1.8%) with mucoepidermoid cancer had bony metastases at D9, L1, and the pelvis after 4 months of treatment. Death occurred in 12 (20.3%; one due to a non-oncologic cause) out of 54 patients during our study. The majority (88%) of patients in our study are male, aged less than 50 (55%). A KPS of 70/>70 was present in 83.3% of patients. The majority of patients in this study are T3 (37%) and T4a (29.6%). Nodal status of patients included 29.6% N0; 27.7% N1, and 35.1% N2. The majority of patients (57.4%) have well-differentiated carcinoma followed by moderately differentiated carcinoma in 38.8% of patients. The difference in death is non-significant when ipsilateral face + neck radiotherapy is compared to bilateral face + neck radiotherapy by Fisher Exact test (statistical value = 0.1246; p > 0.05, statistically not significant), and in other groups, it could not be compared due to the small number of patients. Our results show the non-inferiority of non-composite resection surgery + bilateral face + neck radiotherapy to non-operative radical radiotherapy (bilateral or ipsilateral face wedged radiotherapy + neck radiotherapy), so the majority of patients can be treated by these modalities of treatment. De-escalation of radiotherapy by the use of ipsilateral face wedged + neck radiotherapy is possible as there is no statistically significant difference in local and nodal relapse when compared to bilateral face + neck radiotherapy, and it results in sparing of the opposite side of the face. Buccal mucosa carcinoma in eastern Uttar Pradesh is a very aggressive disease, with 12 (20.3%; one due to a non-oncologic cause) out of 54 patients dying. Our results are different compared to historical data, possibly due to the use of concurrent Cisplatin + 5-Fluorouracil chemotherapy and the lower number of patients in the composite resection group as the majority of patients were frail and did not consent to composite resection.

Analysis of risk factors for persistent PSA after radical prostatectomy: results from a high-volume center in Southeast China

BackgroundFor localized prostate cancer, a comprehensive treatment approach centered around radical prostatectomy (RP) is often their optimal choice. Successful RP can typically reduce prostate-specific antigen (PSA) levels to below 0.1 ng/mL within 6 to 8 weeks postoperatively. However, in clinical practice, 5 to 24% of patients may have a PSA ≥ 0.1 ng/mL at 6 to 8 weeks after surgery, a phenomenon known as PSA persistence. Many studies based on data from Europe and United States have shown an association between PSA persistence and poor postoperative outcomes, further analyzing the risk factors for PSA persistence. However, relevant research based on data from China remains scarce.MethodsRetrospective study of 1,347 prostate cancer patients who underwent RP at the First Affiliated Hospital of Zhejiang University School of Medicine from July 15, 2016, to August 31, 2022. Based on inclusion criteria, univariate and multivariate logistic regression analyses were conducted to explore the independent risk factors for persistent PSA.ResultsAmong the 826 prostate cancer patients after RP, 124 patients experienced persistent PSA. In univariate logistic regression analysis, robot-assisted laparoscopic radical prostatectomy (RARP), preoperative PSA, high-risk group, preoperative International Society of Urological Pathology (ISUP) grades 2–5, postoperative ISUP grades 3–5, percentage of positive cores, cT3, ≥pT3b, extracapsular extension (EPE), seminal vesicle invasion (SVI), positive surgical margins (PSM) and Prostate Specific Antigen Density (PSAD) were all significantly associated with PSA persistence after RP (P < 0.05). In terms of surgical approach, RARP was considered a protective factor against postoperative PSA persistence (OR:0.53, p < 0.05). In multivariate logistic regression analysis, preoperative ISUP grade 4, percentage of positive cores and PSM were independent risk factors of PSA persistence after RP (P < 0.05).ConclusionPreoperative PSA, high-risk group, preoperative ISUP grades 2–5, postoperative ISUP grades 3–5, percentage of positive cores, cT3, ≥pT3b, EPE, SVI, PSM and PSAD were independent risk factors for PSA persistence in prostate cancer patients after RP. This provides assistance for early monitoring and treatment of patients at high risk of persistent PSA in clinical practice.

Outcomes of adjuvant lymph node field radiotherapy and immunotherapy for stage III melanoma

PurposeWith the promising results of immunotherapy in patients with stage III melanoma, the role of adjuvant radiotherapy after resection and complete lymph-node dissection must be reassessed. We evaluate the outcomes and safety of adjuvant radiotherapy and immunotherapy compared to immunotherapy only in patients with resected stage III melanoma. Patients and methodsThis retrospective and single institution study included patients treated for a stage III melanoma with complete lymph-node dissection and adjuvant immunotherapy from January 2019 to December 2022. The radiotherapy associated with immunotherapy group was defined by completion of immunotherapy and adjuvant radiotherapy in the lymph-node dissection area. The primary endpoint was disease-free survival. The secondary endpoints were locoregional progression, incidence of adverse events grade 3 or above and disease-free survival rate in patients with high risk of locoregional recurrence. ResultsThirty-three patients were included. Among them, twelve received adjuvant lymph-node field radiotherapy. The median duration of follow-up was 17months (range: 8–45months). Patients receiving radiotherapy and immunotherapy had a significantly higher disease stage and more frequent extracapsular extension. At 12months, the disease-free survival rate was 66.7 % for the patients receiving immunotherapy alone (95 % CI: 42.5–82.5 %) and 83.3 % for those receiving radiotherapy and immunotherapy (95 % CI: 48.2–95.6 %; P=0.131). The locoregional progression rate was 24 % in patients receiving immunotherapy and 8 % in patients receiving immunotherapy and radiotherapy (P=0.379). After adjuvant treatment, 6 % of patients developed grade 3 or above immunotherapy-related events and none developed grade 3 or above radiation-related adverse events. ConclusionIn patients with stage III melanoma, adjuvant lymph-node field radiotherapy combined with immunotherapy seems to be associated with longer disease-free survival, with acceptable tolerance. However, these results need to be confirmed by long-term and prospective studies.