Node-negative Patients Research Articles

Long-term outcomes and predictors of recurrence in node-negative early stage breast cancer patients.

We evaluated the outcomes, and risk factors for recurrence in patients with early stage node-negative breast cancer in this study. Retrospective data analysis was done on patient treatment records from 1988 to 2018. The patient's demographic, clinical, pathological, and therapeutic characteristics were noted. To evaluate survival analysis and predictors of recurrence, we employed Kaplan-Meier analysis with the log-rank test. A total of 357 patients in all were enrolled in the research. At the time of diagnosis, the median age was 50 (with a range of 18-81). A total of 85.5% of patients had undergone a lumpectomy, while 14.5% had a mastectomy. 78.7% of patients had sentinel lymph node biopsy, and 21.3% had axillary lymph node dissection. In addition, the patients received adjuvant radiotherapy (88.7%), adjuvant endocrine therapy (82.1%), and adjuvant chemotherapy (48.5%). Recurrence of the tumor occurred in 31 (8.7%) patients (local recurrence 45.2% and metastatic disease 54.8%). Ten- and twenty-year recurrence-free survival rates were 92% and 77%. 19 (5.3%) patients had also developed contralateral breast cancer. Ten-year survival rates were 91.6%, and 20-year survival rates were 76.6%, respectively. Aged over 65years (p = 0.004), necrosis (p = 0.002), mitosis (p = 0.003), and nuclear pleomorphism (p = 0.049) were found as statistically significant factors for recurrence in univariate analysis. In the ROC analysis, the largest size of the tumor (over 1.45cm, p = 0.07) remained outside the statistical significance limit in terms of recurrence. Thirty-year outcomes in individuals with early stage, node-negative breast cancer were shown in this study. We found that the recurrence ratios between 10 and 20 years were more frequent than the first 10 years during the follow-up. Despite the small number of patients who experienced a recurrence, we demonstrated that, in univariate analysis, being older than 65 and having some pathological characteristics (nuclear pleomorphism, mitosis, and necrosis) were statistically significant factors for disease recurrence.

The budget impact of utilizing the Oncotype DX Breast Recurrence Score test from a US healthcare payer perspective

Background and objectivesThe Oncotype DX Breast Recurrence Score test is used to estimate distant recurrence risk of hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2–) early-stage breast cancer and inform decisions on the use of adjuvant chemotherapy. A model-based budget impact analysis compared the Oncotype DX test in combination with clinical–pathological risk against using clinical–pathological risk alone for HR+/HER2– node-negative (N0) and node-positive (N1; 1–3 axillary lymph nodes) early-stage breast cancer patients.Materials and methodsTest and medical costs associated with treatment of breast cancer were assessed through a US healthcare payer perspective. Distributions of patients by Recurrence Score result and distant recurrence probabilities with chemo-endocrine and endocrine therapy were derived from the TAILORx (N0) and RxPONDER (N1) trials. Changes in budget impact were evaluated over a 5-year horizon for a 1,000,000-member hypothetical health plan.ResultsWith the Oncotype DX test, there was an incremental budget impact of $261,067 (per member per month (PMPM): $0.004), in the N0 population, and $56,143 (PMPM: $0.001) in the N1 population over the 5-year period. The largest budget impact reduction in the N0 population was attributed to reduced breast cancer recurrence costs (incremental: −$633,457, PMPM: −$0.011), while chemotherapy sparing reduced costs in the N1 population (incremental: −$94,884, PMPM: −$0.002).ConclusionThe clinical benefit of using the Oncotype DX test to inform adjuvant chemotherapy decisions has been shown in multiple randomized controlled trials. This analysis demonstrated that while using the Oncotype DX test to inform adjuvant chemotherapy decisions may slightly increase US healthcare costs over an initial 5-year time horizon (driven by a cost increase in the first year with cost savings reflected in remaining 4 years), there is significant scope for cost savings when assessing beyond this period due to avoided downstream costs of distant recurrence and long-term chemotherapy adverse events. PMPM costs also remain low across all populations examined, demonstrating a close-to-neutral budget impact.

ASO Visual Abstract: Intraoperative Pathology Assessment May Lead to Overtreatment of the Axilla in Clinically Node-Negative Breast Cancer Patients Undergoing Upfront Mastectomy.

ASO Visual Abstract: Intraoperative Pathology Assessment May Lead to Overtreatment of the Axilla in Clinically Node-Negative Breast Cancer Patients Undergoing Upfront Mastectomy.

ASO Visual Abstract: Breast-Conserving Therapy is Associated with Improved Survival without an Increased Risk of Locoregional Recurrence Compared to Mastectomy in Both Clinically Node Positive and Node Negative Breast Cancer Patients.

ASO Visual Abstract: Breast-Conserving Therapy is Associated with Improved Survival without an Increased Risk of Locoregional Recurrence Compared to Mastectomy in Both Clinically Node Positive and Node Negative Breast Cancer Patients.

Development and validation of a prognostic nomogram for predicting cancer-specific survival in lymph node-negative elderly esophageal cancer patients: A SEER-based study.

In this study, we explored the prognostic risk factors of elderly patients (≥65 years old) with lymph node-negative esophageal cancer (EC) and established a nomogram to evaluate the cancer-specific survival of patients. The surveillance, epidemiology, and end results database was used to collect data on patients diagnosed with EC. Univariate and multivariate Cox analyses were used to determine independent prognostic factors, and the nomogram for predicting cancer-specific survival of EC patients was constructed based on the independent prognostic factors obtained from the multivariate Cox analysis. To evaluate the predictive ability of the nomogram, calibration curves, concordance index (C-index), receiver operating characteristic curves, and decision curve analysis were conducted. Kaplan-Meier method was used to analyze the long-term outcomes of EC patients with different risk stratifications. A total of 3050 cases with lymph node-negative EC were randomized into the training cohort (1525) and the validation cohort (1525). Cancer-specific mortality at 1, 3, and 5 years in the entire cohort was 30.7%, 41.8%, and 59.2%, respectively. In multivariate Cox analysis, age (P < .001), marital status (P < .001), tumor size (P < .001), Tumor-node-metastasis stage (P < .001), chemotherapy (P = .011), radiotherapy (P < .001), and surgery (P < .001) were independent prognostic factors. The C-index for the training cohort was 0.740 (95% confidence interval [CI]: 0.722-0.758), and the C-index for the validation cohort was 0.738 (95% CI: 0.722-0.754). The calibration curve demonstrated the great calibration ability of the nomogram. Based on the area under the receiver operating characteristic curve, the nomogram demonstrated a higher sensitivity than the tumor-node-metastasis stage. Decision curve analysis showed the good clinical utility of the nomogram. The risk stratification system was established using the Kaplan-Meier curve and verified by the log-rank test (P < .001). The nomogram and risk stratification system can improve the accuracy of prediction to help clinicians identify high-risk patients and make treatment decisions.

Assessment of level IIB lymph nodes in oral cancer - Should we spare or care?

Objectives The extent of neck dissection over the years has evolved from a radical neck dissection to a super-selective neck dissection with an attempt to achieve a balance between oncological safety and acceptable morbidity. There is an ongoing debate concerning dissection of level IIB in both node negative and positive patients, primarily due to the low incidence of metastasis in this region and possible spinal accessory nerve injury. In this study, we intended to find the rate of metastasis to level IIB nodes in patients who were treated with neck dissection for oral cancers. Material and Methods Patients with squamous cell carcinoma of the oral cavity who underwent neck dissection were analyzed. Patients with clinically node negative (cN0) disease underwent selective neck dissection (SND), whereas patients with clinically node positive (cN+) disease underwent modified radical neck dissection (MRND). Results Out of the total 34 patients, 12 patients underwent MRND and 22 patients underwent SND. In the MRND group, three patients (25%) had positive level IIB nodes. The median number of IIB nodes removed was two and the median number of positive IIB nodes was one. In the SND group, the median number of IIB nodes removed was three and none of the patients had positive level IIB node. Conclusion In oral cancer with cN+, routine dissection of level IIB nodes has both therapeutic and prognostic values. Whereas, in patients with cN0, routine dissection of level IIB nodes can be omitted. Further large volume studies are needed on cN0 disease.

Combining the 31-gene expression profile test for cutaneous melanoma with the American Joint Committee on Cancer staging identifies the highest-risk patients with stage I-II disease

Introduction: Management guidelines for cutaneous melanoma (CM) are based on patients’ recurrence risk by stage. Most newly diagnosed patients (88%) will be categorized as node-negative (stage I-II) and will be considered low-risk. However, because of the size of this group, the small percentage of stage I-II individuals who do die of melanoma account for the majority of melanoma-associated deaths. In collaboration with the Surveillance, Epidemiology, and End Results (SEER) program, we demonstrated, in a large, unselected cohort of clinically tested patients, that the 31-GEP test identifies those individuals with stage I-II disease, who have higher risk of melanoma-specific death and who may benefit from more aggressive management. &#x0D; Methods: SEER registries linked individuals diagnosed with CM between 2013-2018 were linked to data for 31-GEP-tested patients (N=9,207 after exclusions). For this study, analysis focused on the subset reported as node-negative (N=6,301). Patient 5-year melanoma-specific survival (MSS) was estimated using Kaplan-Meier analysis and the log-rank test for patients considered by the 31-GEP to be low-risk (Class 1A), intermediate-risk (Class 1B/2A), or high-risk (Class 2B). Multivariable Cox regression analysis was used to evaluate significant predictors of melanoma-specific death. Notably, at the time of diagnosis, none of the immune checkpoint inhibitor or targeted signal transduction therapies were approved for use in node-negative patients, providing a largely contemporary therapy naïve cohort. &#x0D; Results: Patients with a Class 2B 31-GEP result had significantly lower 5-year MSS than patients with Class 1B/2A or Class 1A results (85.0% vs. 95.6% vs. 97.9%, p&lt;0.001). The 31-GEP Class 2B result (HR=4.08, p&lt;0.001) was the strongest predictor of melanoma-specific death. Breslow thickness (HR=1.16, p=0.002), presence of ulceration (HR=2.10, p=0.006), and age (HR=1.05, p&lt;0.001) were also significant predictors of melanoma-specific death. The 31-GEP had a sensitivity of 78.4% and a negative predictive value (NPV) of 99.4%. Combining the 31-GEP Class result with AJCC staging could increase the sensitivity to 82.0% while maintaining a high NPV (99.4%). &#x0D; Conclusion: In a large, unselected cohort of patients with stage I-II CM, the 31-GEP Class 2B identified patients with a high risk of progression and death from melanoma who should be considered for more aggressive management. Conversely, the high NPV suggests that the 31-GEP reliably identifies patients at low risk of tumor progression who could safely avoid intensive surveillance and intervention.

Intraoperative Pathology Assessment May Lead to Overtreatment of the Axilla in Clinically Node-Negative Breast Cancer Patients Undergoing Upfront Mastectomy.

Randomized trials have established the safety of observation or axillary radiation (AxRT) as an alternative to axillary lymph node dissection (ALND) in patients with limited nodal disease who undergo upfront surgery. Variability remains in axillary management strategies in cN0 patients undergoing mastectomy found to have one to two positive sentinel lymph nodes (SLNs). We examined the impact of intraoperative pathology assessment in axillary management in a national cohort of AMAROS-eligible mastectomy patients. The National Cancer Database was used to identify AMAROS-eligible cT1-2N0 breast cancer patients undergoing upfront mastectomy and SLN biopsy (SLNB) and found to have one to two positive SLNs, from 2018 to 2019. We constructed a variable defining intraoperative pathology as 'not performed/not acted on' if ALND was either not performed or performed at a later date than SLNB, or 'performed/acted on' if SLNB and ALND were completed on the same day. Adjusted multivariable analysis examined predictors of treatment with both ALND and AxRT. Overall, 8222 patients with cT1-2N0 disease underwent upfront mastectomy and had one to two positive SLNs. Intraoperative pathology was performed/acted on in 3057 (37.2%) patients. These patients were significantly more likely to have both ALND and AxRT than those without intraoperative pathology (41.0% vs. 4.9%; p<0.001). On multivariate analysis, the strongest predictor of receiving both ALND and AxRT was use of intraoperative pathology (odds ratio 8.99, 95% confidence interval 7.70-10.5; p<0.001). We advocate that consideration should be made for omission of routine intraoperative pathology in mastectomy patients likely to be recommended postmastectomy radiation to minimize axillary overtreatment with both ALND and AxRT in appropriate patients.

The Diagnostic Value of the Sentinel Node Procedure to Detect Occult Lymph Node Metastases in PSMA PET/CT Node-Negative Prostate Cancer Patients.

Our objective was to assess the diagnostic value of the sentinel node (SN) procedure for lymph node staging in primary intermediate- and high-risk prostate cancer patients with node-negative results on prostate-specific membrane antigen PET/CT (miN0). Methods: From 2016 to 2022, 154 patients with primary, miN0 PCa were retrospectively included. All patients had a Briganti nomogram-assessed nodal risk of more than 5% and underwent a robot-assisted SN procedure for nodal staging. The prevalence of nodal metastases at histopathology and the occurrence of surgical complications according to the Clavien-Dindo classification were evaluated. Results: The SN procedure yielded 84 (14%) tumor-positive lymph nodes with a median metastasis size of 3 mm (interquartile range, 1-4 mm). In total, 55 patients (36%) were reclassified as pN1. A complication of Clavien-Dindo grade 3 or higher occured in 1 patient (0.6%). Conclusion: The SN procedure classified 36% of patients with miN0 prostate cancer with an elevated risk of nodal metastases as pN1.

Forecasting patient-specific dosimetric benefit from daily online adaptive radiotherapy for cervical cancer

Objective. Adaptive Radiotherapy (ART) is an emerging technique for treating cancer patients which facilitates higher delivery accuracy and has the potential to reduce toxicity. However, ART is also resource-intensive, Requiring extra human and machine time compared to standard treatment methods. In this analysis, we sought to predict the subset of node-negative cervical cancer patients with the greatest benefit from ART, so resources might be properly allocated to the highest-yield patients. Approach. CT images, initial plan data, and on-treatment Cone-Beam CT (CBCT) images for 20 retrospective cervical cancer patients were used to simulate doses from daily non-adaptive and adaptive techniques. We evaluated the coefficient of determination (R2) between dose and volume metrics from initial treatment plans and the dosimetric benefits to the and from adaptive radiotherapy using reduced 3 mm or 5 mm CTV-to-PTV margins. The LASSO technique was used to identify the most predictive metrics for The three highest performing metrics were used to build multivariate models with leave-one-out validation for Main results. Patients with higher initial bowel doses were correlated with the largest decreases in Bowel from daily adaptation (linear best fit R2 = 0.77 for a 3 mm PTV margin and R2 = 0.8 for a 5 mm PTV margin). Other metrics had intermediate or no correlation. Selected covariates for the multivariate model were differences in the initial and using standard versus reduced margins and the initial bladder volume. Leave-one-out validation had an R2 of 0.66 between predicted and true adaptive benefits for both margins. Significance. The resulting models could be used to prospectively triage cervical cancer patients on or off daily adaptation to optimally manage clinical resources. Additionally, this work presents a critical foundation for predicting benefits from daily adaptation that can be extended to other patient cohorts.

A combined approach for individualized lymphadenectomy in gastric cancer patients.

Introduction: Gastric cancer ranks as the fifth most common cancer globally. The presence of lymph node metastasis is a significant prognostic factor influencing survival. Postoperative morbidity and nodal staging accuracy are heavily affected by the extent of lymph node dissection. Our study aimed to explore the potential integration of two contemporary methods, sentinel node navigation surgery (SNNS) and the Maruyama Computer Program (MCP), to improve the accuracy of nodal staging. Materials and methods: We conducted a prospective data collection involving patients with gastric adenocarcinoma from 2008 to 2018 at the Department of Surgery, University of Debrecen, Hungary. Data from 100 consecutive patients were collected. The primary and secondary endpoints included evaluating the rate of node-negative patients and the diagnostic accuracy of our combined approach. Results: Sentinel node mapping was successful in 97 out of 100 patients. We found that using the threshold value of the Maruyama Index (MI) ≥ 28, all metastatic stations of sentinel-node-negative patients could be identified. Our method achieved 100% sensitivity and negative predictive value, with a specificity of 60.42% (95% CI = 46.31%-72.98%). Discussion: The combined application of SNNS and MCP has proven to be an effective diagnostic technique in the synergistic approach for identifying metastasis-positive lymph node stations. Despite its limitations, this combination may assist clinicians in customizing lymphadenectomy for gastric cancer patients.

Breast-Conserving Therapy is Associated with Improved Survival Without an Increased Risk of Locoregional Recurrence Compared with Mastectomy in Both Clinically Node-Positive and Node-Negative Breast Cancer Patients.

Randomized trials demonstrated equivalent survival between breast-conserving surgery combined with radiotherapy (BCT) and mastectomy alone. Contemporary retrospective studies using pathological stage have reported improved survival with BCT. However, pathological information is unknown before surgery. To mimic real-world surgical decision-making, this study assesses oncological outcomes by using clinical nodal status. Female patients aged 18-69 years who were treated with upfront BCT or mastectomy between 2006 and 2016 for T1-3N0-3 breast cancer were identified by using prospective, provincial database. The patients were divided into clinically node-positive (cN+) and node-negative (cN0) strata. Multivariable logistic regression was used to assess the effect of local treatment type on overall survival (OS), breast cancer-specific survival (BCSS), and locoregional recurrence (LRR). Of 13,914 patients, 8228 had BCT and 5686 had mastectomy. Mastectomy patients had higher-risk clinicopathological factors: pathologically positive axillary staging was 21% in BCT and 38% in mastectomy groups. Most patients received adjuvant systemic therapy. For cN0 patients, 7743 had BCT and 4794 had mastectomy. On multivariable analysis, BCT was associated with improved OS (hazard ratio [HR] 1.37, p<0.001) and BCSS (HR 1.32, p<0.001), whereas LRR was not different between the groups (HR 0.84, p=0.1). For cN+ patients, 485 had BCT and 892 had mastectomy. On multivariable analysis, BCT was associated with improved OS (HR 1.46, p=0.002) and BCSS (HR 1.44, p=0.008), whereas LRR was not different between the groups (HR 0.89, p=0.7). In the era of contemporary systemic therapy, BCT was associated with better survival than mastectomy, without an increased risk of locoregional recurrence for both cN0 and cN+ presentations.

Node-negative colon cancer: histological, molecular, and stromal features predicting disease recurrence

BackgroundWithin the group of node-negative colon cancer patients, presumed to have a good prognosis, a significant percentage of patients develops cancer-recurrence. Current high-risk features prove inadequate to select these particular high-risk patients. In the process of tailor-made care and shared decision-making the need to identify these patients grows. In this study we investigate the value of adding molecular markers and the tumour-stroma ratio (TSR) to conventional histological tumour staging methods to improve the selection of high risk patients.MethodsWe retrospectively analysed 201 patients diagnosed with TNM-stage I-II colon cancer and treated by complete oncological resection between November 1st 2002 and December 31st 2012 at the Jeroen Bosch Hospital. Conventional histological tumour staging, BRAF mutations, KRAS mutations, MSI status and TSR were determined. Differences between groups based on TSR and mutation status, in disease free survival were analysed using Cox-Regression analyses.ResultsPoorly differentiated histology (p = 0.002), high-TSR (p = 0.033), BRAF-mutation (p = 0.008) and MSI (p = 0.011) were identified as significant risk factors for cancer recurrence. The risk of recurrence increased in the presence of both a BRAF-mutation and high-TSR compared to the absence of both factors or presence of only one factor (HR = 3.66 BRAF-mt/TSR-low (p = 0.006), HR 2.82 BRAF-wt/TSR-high (p = 0.015), HR = 4.39 BRAF-mt/TSR-high (p = 0.023)). This was also seen in tumours with MSI and high-TSR (HR = 2.46 MSS/TSR-high (p = 0.041), HR = 3.31 MSI/TSR-high (p = 0.045).ConclusionJudging by the higher HR for the combination of the prognostic factors TSR and BRAF compared to the HRs of these prognostic factors individually, the prognostication for disease free survival can be improved by determining both TSR and BRAF instead of BRAF alone, as is done in current daily practise. In this study MSI also shows additional value to TSR in the prognostication of disease free survival. Adopting TSR into daily diagnostics will be of additional value next to currently used molecular markers in risk stratification of patients with node negative colon cancer and is therefore advised.

Versatility of Submental Island Flap in N0 Neck in Oral Malignancies- A Retrospective Analysis of 50 Cases.

Submental flap is a gaining popularity as a reconstruction of orofacial defects in post-ablative defects, especially in situations where free flap services are not available or feasible. The background of this study was to demonstrate the oncological safety and benefits of this flap in oral cavity reconstruction. A retrospective analysis of 50 patients from the age group 28 to 70 years with oral cavity cancers of different subsites, who underwent submental flap reconstruction from 2018 to 2022 at our hospital for various ablative defects of oral cavity, were included in the study. We have reviewed the parameters like flap complications, post-operative mouth opening after 1 year and nodal recurrence. There were 37 males and 13 females patients in the study. 29(58%) patients had buccal cancers, 11(22%) patients had tongue cancer, 7(14%) patients had retromolar trigone cancer and 3(6%) had gingivo-buccal cancers. All patients underwent resection with ipsilateral selective neck dissection after flap was harvested. Complete flap loss was observed in 1(2%) patient, whereas as the flap dehiscence was seen in 3(6%) patients. Mean follow-up was 12 months. There were 3(6%) cases of nodal recurrence on the same side of flap after a mean time of 5 months of surgery. Inter-Incisal mouth opening was 20-30mm in 68% of the cases. On the 1 year follow-up, all the patients were alive with no mortality. Oncologic outcome in terms of overall survival was found to be 94% in patients reconstructed with submental flap which makes it versatile for oral cavity reconstructions. Submental flap is a robust flap for oral cavity reconstruction. However, preoperative selection of clinically neck node-negative patient is extremely important as it has potential risk of occult metastasis and oncologic safety.

Comparison of oncological outcomes between sentinel lymph node biopsy and complete lymphadenectomy for endometrial cancer.

Sentinel lymph node (SLN) mapping allows node-negative patients to be spared from the surgical comorbidities associated with total lymphadenectomy. This study aimed to evaluate the oncological outcomes of SLN biopsy versus complete lymph node dissection in patients with early-stage endometrial carcinoma. Retrospective analyses were performed in patients with pathologically confirmed endometrioid endometrial carcinoma, who underwent minimally invasive surgical staging with SLN biopsy or complete lymph node dissection at Yonsei Cancer Center between 2015 and 2019. A total of 301 patients were included in this study. Eighty-two patients underwent SLN biopsy, while 219 underwent complete lymph node dissection. There were no significant differences in patient characteristics between the two groups. In terms of operative characteristics, the SLN biopsy-only group had a significantly shorter surgical duration (p < 0.001) than the lymphadenectomy group. The mean follow-up period was 41.4 months. There were no differences in progression-free survival (PFS) and overall survival (OS) between the two groups (SLN biopsy vs. complete lymph node dissection; p = 0.798 and 0.301, respectively). Multivariate analysis revealed that SLN biopsy was not an independent prognostic factor for PFS or OS. Our results showed that SLN biopsy provided oncological outcomes similar to those of lymphadenectomy.

Evaluation of PAM50 intrinsic subtypes and risk of recurrence (ROR) scores in premenopausal women with early-stage HR+ breast cancer: A secondary analysis of the SOFT trial.

504 Background: The landmark Suppression of Ovarian Function Trial (SOFT) in premenopausal breast cancer patients revealed that the addition of ovarian function suppression (OFS) to adjuvant endocrine therapy with either tamoxifen (T+OFS) or exemestane (E+OFS) reduces the risk of recurrence compared with adjuvant tamoxifen alone. There are no biomarkers to aid decision-making about intensification of endocrine therapy with OFS. The purpose of this study is to assess the prognostic and predictive ability of PAM50 intrinsic subtypes and ROR scores in premenopausal women with HR+/HER2- breast cancer in the SOFT trial. Methods: Gene expression analyses were performed via the NanoString Breast Cancer 360 assay on RNA isolated from FFPE tumor samples from the SOFT trial that were HR+/HER2- (n=1245/3047). PAM50 subtype and ROR score were determined centrally by NanoString Technologies (Seattle, WA, USA), blinded to clinical characteristics, treatment and outcome. Median follow-up was 12 years. Primary endpoint in this study was distant recurrence-free interval (DRFI). Secondary endpoints were breast cancer-free interval (BCFI) and disease-free survival (DFS). Kaplan-Meier analysis and Cox proportional hazards regression models, stratified by prior chemotherapy and lymph node status, were used to evaluate the predictive performance of PAM50 intrinsic subtypes and ROR categories (low vs intermediate vs high), and secondarily ROR score as a continuous variable. We also investigated differences between very young (&lt;40yrs) vs young (&gt;40yrs) women. Results: Tumor samples from 1084/1245 (87%) patients successfully completed PAM50 testing and are included in this analysis. Patient characteristics in this cohort were similar to the entire SOFT trial population. Intrinsic subtype and ROR category distribution is described below. Subtype distribution significantly differed between very young vs young premenopausal women, with fewer luminal A and more luminal B and non-luminal tumors seen in the very young (p&lt;0.001). The ROR score distribution also differed significantly: in node-negative patients there were significantly more ROR-high scores amongst very young compared to young women (36% vs 14%, p&lt;0.001). Conclusion: Breast cancer diagnosed in very young women has aggressive disease biology. Prognostic and predictive analyses of both intrinsic subtypes and the ROR score are ongoing and will be presented at the meeting. Clinical trial information: NCT00066690 . [Table: see text]

A thirty-three gene-based signature predicts lymph node metastasis and prognosis in patients with gastric cancer

Recently, several studies have indicated the great potential of gene expression signature of the primary tumor in predicting lymph node metastasis; however, few current gene biomarkers can predict lymph node status and prognosis in gastric cancer (GC). Thus, we used the RNA-seq data from The Cancer Genome Atlas (TCGA) to identify differentially expressed genes between pathological lymph node-negative (pN0) and positive (pN+) patients and to establish a gene signature that could predict lymph node metastasis. Meanwhile, the robustness of identified gene signatures was validated in an independent dataset Asian Cancer Research Group (n = 300). In this study, our thirty-three gene-based signature was highly correlated with lymph node metastasis and could successfully discriminate pN + patients in the training set (Area under the receiver operating characteristic curve = 0.951). Moreover, Disease-free survival (P = 0.0029) and overall survival (P = 0.026) were significantly worse in high-risk compared with low-risk patients overall and when confined to pN0 patients only (P < 0.0001). Of note, this gene signature also proved useful in predicting lymph node status and survival in the validation cohort. The present study suggests a thirty-three gene-based signature that could effectively predict lymph node metastasis and prognosis in GC.

Wolf in sheep’s clothing: Effect of primary lung tumor cells equipped with elevated neuron-like properties on brain metastases formation.

e14009 Background: It is clinically significant to decipher the mechanisms underlying lung cancer-associated brain metastases. However, comparative studies on primary tumors between patients with and without brain metastases failed to unveil such mechanisms. Moreover, the clinical observation that the incidence of brain metastases after resection of the primary tumor was as high in lymph node-negative (non-LNM) patients as in those with lymph node metastases (LNM) challenges our established knowledge that lymph node staging correlates with distant metastases. Here, we hypothesized that tumor cells in non-LNM patients might acquire a unique mechanism to develop brain metastases. Methods: We ran whole-transcriptome sequencing and methylation sequencing on paired primary tumor and brain metastases samples from 15 NSCLC patients. We compared the differentially expressed genes (DEGs) between patients with LNM and non-LNM patients. Results: Pathway enrichment analysis showed that GO and KEGG pathways associated with neuronal transmission and synaptic signaling were upregulated in primary tumors of the non-LNM group vs. that of the LNM group. In contrast, brain metastases revealed an inversed trend of differential expression for these pathways between non-LNM and LNM groups. Exploratory validation at methylation level revealed that high expression of the neuronal transmission-associated gene GABRG3 correlated with hypomethylation of this gene (R=-0.39, p=0. 042), responsive to increased expression of GABRG3 in brain metastases. Brain metastases expressed higher neuronal transmission-related signatures than paired primary tumors. Intriguingly, this upregulation of tumor-neuron interactions was more pronounced in patients with lymph node metastases, suggesting that i) lymph node metastases might aid primary tumor to develop brain metastases by promoting the adaptation of tumor cells to the brain microenvironment, while ii) non-LNM patients already acquired neuron-like traits at primary sites, heralding the potential of brain metastases. Conclusions: The hypothetical mechanism of lymph node-negative lung cancer developing brain metastases might be that these tumor cells acquired properties of brain cells as early as in primary sites, masking themselves as ‘sheep’ to communicate with the host’s brain cells, and eventually unmasked as ‘wolf’: brain metastases. Further functional studies are warranted to validate this hypothesis.

Extended versus standard pelvic lymph node dissection yields no difference in 3-year biochemical recurrence rates.

extended pelvic lymph node dissection (ePLND) increases the detection rate of lymph node positive prostate cancer compared to a standard pelvic lymph node dissection (sPLND). However, improvement of patient outcomes remains questionable. Here we report and compare 3-year postoperative PSA recurrence rates between patients that underwent sPLND versus ePLND at the time of prostatectomy. 162 patients received a sPLND (which involvedremoval of periprostatic, external iliac, and obturator lymph nodes bilaterally), and 142 patients received an ePLND (which involved removal of periprostatic, external iliac, obturator, hypogastric, and common iliac nodes bilaterally). Decision to undergo ePLND versus sPLND at our institution was changed in 2016 based on the National Comprehensive Cancer Network guideline. The median follow-up time was 7 and 3years for sPLND and ePLND patients, respectively. All node-positive patients were offered adjuvant radiotherapy. Kaplan-Meier analysis was carried out to assess the impact of a PLND on early postoperative PSA progression-free survival. Subgroup analyses were done for node-negative and node-positive patients, as well as Gleason score. Gleason score and T stage were not significantly different between patients who received an ePLND and sPLND. The pN1 rate for ePLND and sPLND were 20% (28/142) and 6% (10/162), respectively. There was no difference in the use of adjuvant treatments in the pN0 patients. Significantly, more ePLND pN1 patients received adjuvant androgen deprivation therapy (25/28 vs. 5/10 P=0.012) and radiation (27/28 vs. 4/10 P=0.002). Yet, no difference in biochemical recurrence between ePLND and sPLND was observed (P=0.44). This remained true in subgroup analyses of node-positive (P=0.26), node-negative (P=0.78), Gleason Score 6-7 (P=0.51), and Gleason Score 8-10 (P=0.77). PLND provided no additional therapeutic benefit, even though ePLND patients were significantly more likely to have node-positive disease and undergo adjuvant treatment, compared to a sPLND.

National trends in neoadjuvant chemotherapy utilization for cT1-2 N0 triple negative breast cancer: Did the CREATE-X trial impact treatment patterns?

e12599 Background: Neoadjuvant chemotherapy (NAC) for operable breast cancer allows for in-vivo assessment of chemotherapy response with survival and therapeutic implications. In 2017, the Capecitabine for Residual Cancer as Adjuvant Therapy (CREATE-X) trial demonstrated significant improvement in survival with the addition of adjuvant capecitabine in patients with triple negative breast cancer (TNBC) and residual disease after NAC. These results provided the rationale for NAC even in early stage TNBC. The aim of this study was to assess U.S. national rates of NAC utilization in early-stage node-negative TNBC patients before and after the release of CREATE-X and to assess factors associated with receiving NAC vs adjuvant chemotherapy (AC). Methods: The National Cancer Database was queried for women with cT1-2N0M0 TNBC from 2014–19. NAC utilization was collected and categorized as 2014-15 (pre-CREATE-X), 2016-17 (transition yrs), and 2018-19 (post-CREATE-X). Those who did not receive chemotherapy were excluded. NAC use over time was analyzed via multivariable logistic regression (MLR). Clinical and demographic factors associated with NAC vs AC utilization were assessed using ANOVA, Chi-squared, and Fisher Exact tests. A MLR model was used to determine predictors of receipt of NAC vs AC. Results: 55,633 women were treated from 2014-19: 26.9% with NAC, 52.4% with AC, and 20.7% received no chemotherapy (median ages 53, 59, and 71yrs, respectively, p &lt; 0.01). Most had cT1c (32.7%, n = 18,190) or cT2 (41.95%, n = 23,331) tumors and 99% had invasive ductal pathology. NAC utilization significantly increased over time, 19.5% (n = 3,465 of 17,777) in 2014-15, 27.1% (n = 5,140 of 18,985) in 2016-17, and 33.6% (n = 6,337 of 18,871) in 2018-19 (p &lt; 0.01). On MLR analysis, increased use of NAC was associated with younger age ( &lt; 50yrs), non-Hispanic white patients, having no comorbidities, having a cT2 tumor, grade 2 disease, and care at an academic or integrated network cancer program (p &lt; 0.05 for all). Patients with Medicare and Medicaid insurance were less likely to receive NAC (p &lt; 0.01). Patients who traveled &gt; 60 miles to their treating facility were more likely to receive NAC (p &lt; 0.01). Conclusions: From 2014–19, NAC utilization increased for patients with cT1-2N0M0 TNBC coinciding with the release of the CREATE-X results. Findings demonstrate the significance of the multidisciplinary oncology team in developing individualized treatment plans based on emerging clinical trial evidence. Racial, socioeconomic, and access disparities were observed in NAC utilization and warrants further investigation and interventions to ensure equitable care. [Table: see text]