Positive Lymph Research Articles

The impact of uncertainty resection on the prognosis of non-small cell lung cancer

Objective: To explore the impact of uncertain resection on postoperative survival in non-small cell lung cancer. Methods: This is a retrospective cohort study. A retrospective analysis was conducted on the data of 477 patients with non-small cell lung cancer who underwent lobectomy in the Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University from December 2012 to December 2013. There were 302 males and 175 females, aged (59±8) years (range: 27 to 79 years). According to the surgical resection criteria issued by the International Association for the Study of Lung Cancer, the patients were divided into the intact resection group (R0 group, 286 cases) and the uncertain resection group (R (un) group, 191 cases). Clinical data between the two groups were compared using χ2 test, and propensity score matching (PSM) was performed on patients using the R language, with matching variables including gender, age, smoking history, adjuvant therapy, TNM stage, pathological type, and tumor site. The nearest-neighbor method was used for 1∶3 matching and the caliper value was 0.02. The survival curve was plotted using the Kaplan-Meier method and compared using the Log-rank test. The Cox proportional hazards regression model was used to identify risk factors in overall survival (OS). Subgroup analysis was based on TNM staging and mediastinal lymph node metastasis status. Results: In the R (un) group, 68 patients had positive lymph in the highest group and 129 patients did not undergo complete dissection of the mediastinal lymph nodes. The baseline data for the R0 group and the R (un) group were corrected using PSM, and a total of 369 patients were successfully matched, including 227 cases in the R0 group and 142 cases in the R (un) group. After PSM, the 5-year survival rates of the R0 group and the R (un) group were 64.3% and 52.1%, respectively (P=0.021). The 5-year survival rates of stage Ⅰ, Ⅱ, and Ⅲ patients were 85.2%, 65.9%, and 34.8%, respectively (P<0.01). TNM stage (χ2=46.913, P<0.01), pathological classification of adenosquamous cell carcinoma (HR=5.970, 95% CI: 3.117 to 11.431, P<0.01) and R (un) resection (HR=1.512, 95% CI: 1.065 to 2.147, P=0.021) were prognostic factors for postoperative survival. Subgroup analysis showed that in stage Ⅲ patients, 5-year survival rates of the R0 group and the R (un) group after resection were 45.8% and 9.5%, respectively (P=0.002). Among patients with mediastinal lymph node metastasis, 5-year survival rates of the R0 group and the R (un) group were 50.6% and 7.1%, respectively (P<0.01). Conclusions: TNM staging, pathological type, and R (un) resection are prognostic factors for overall postoperative survival in non-small cell lung cancer. In stage Ⅰ and Ⅱ patients, R (un) is not a prognostic factor for postoperative survival of non-small cell lung cancer. In patients with stage Ⅲ and mediastinal lymph node metastasis, R (un) is a prognostic factor for non-small cell lung cancer after surgery.

Investigating the outcome of vascular emboli in patients with breast cancer.

e13116 Background: Vascular emboli (VE) represent a critical event in breast cancer pathophysiology. Despite their clinical relevance, their relative impact on breast cancer outcomes remains underexplored. In this study, we delve into comparing the survival outcomes and recurrence rates of patients with and without VE in patients with breast cancer (BC) and adjust for other patient-related variables. Methods: This study was designed based on a retrospective cohort of pathologically confirmed de novo, local, or metastatic recurrence BC female patients diagnosed between 2020 and 2022 and aged &gt; 18 years. Kaplan-Meier curves and Cox proportional hazards models were used to estimate the effect of vascular emboli on survival and recurrence while controlling other reviewed demographic, clinic, pathologic, and therapeutic features following a course of adjuvant or neo-adjuvant treatments. Results: A total of 501 patients were eligible for this study (216 patients without VE vs. 285 patients with VE). The median follow-up was 274 (IQR: 195–523) days. In the group of patients with positive VE, the median age at diagnosis was 49 years, and the median progression-free survival (mPFS) was 881 (95% CI: 856, 1555) days; Patients with bilateral BC have a poorer mPFS of 515 (95% CI: 411, Not Estimable [NE]), while right BC was associated with a better outcome of 1,035 (95% CI: 869, NE) days (p = 0.001). Moreover, patients with positive hormonal receptors (HR &gt;=10%) who benefited from endocrine therapies have a better PFS of 974 (95% CI: 872, NE) days compared to those with negative HR (&lt;10%) of 656 (95% CI: 586, NE) days (p = 0.02). In addition to the molecular profile, TNBC was associated with poorer survival 579 (95% CI: 553, NE), compared to RH-/HER2+ 675 (95% CI: 635, NE), RH+/HER2- 935 (95% CI: 777, NE), and RH+/HER2+ 1,133 (95% CI: 856, NE) days (p &lt; 0.001). Surgery was associated with better mPFS (935 (95% CI: 869, NE) days compared to neo-adjuvant or palliative patients 856 (95% CI: 635, NE) (p = 0.002). In the group of patients with negative VE, the median age was 48 years. The mPFS was 852 (95% CI: 789–996) days. Patients presented with positive lymph (N2) have a worse PFS of 611 (95% CI: 505, NE) days; in addition, patients with HER2=0 have a worse PFS of 775 (95% CI: 595, 1,320) days compared to HER2 1+ or non-amplified HER2 2+ 928 (95% CI: 840, NE) days, while no statistically significant differences between patients who received different treatment options (HER2 TKI, chemotherapy, radiotherapy, and endocrine therapy) were found. Conclusions: These findings emphasize the importance of considering VE status and hormonal receptor expression in tailoring treatment strategies for BC patients. Identifying high-risk individuals who may benefit from aggressive or novel therapies remains crucial for improving outcomes. Further research is warranted to validate these results and guide clinical decision-making.

Identifying the driver histology responsible for the inferior clinicopathologic features associated with plasmacytoid bladder cancer.

e16505 Background: Plasmacytoid urothelial cancer (PUC) is notorious for its spread along fascial planes which reportedly induces worse clinicopathologic. Usually, PUC is present with Conventional UC (CUC); however, the precise assessment of the PUC component in key pathological findings and its effect on clinical behavior has not been delineated. Methods: We performed a retrospective review of patients with PUC who underwent cystectomy at Moffitt Cancer Center between 2012-2022. Repeat histological review of all specimens by specialty trained genitourinary pathologists was performed (AV, ED). Positive margins and lymph nodes were examined and classified by histological subtype. We calculate the proportion of tissue sections with peri-vesical fat invasion in tumor tissue sections submitted from cystectomy specimen in pT3 cases as the microscopic surrogate for macroscopic pT3 sub staging (termed Peri-vesical Fat Invasion Ratio, PFIr). Pearson’s correlation coefficient was used to measure strength and direction of relationship between variables. Kaplan-Meier (KM) analysis was performed for overall survival (OS). Results: Population consists of 44 patients undergoing cystectomy for PUC. Median age was 70 (IQR 63-75) years old with 82% being male. Majority of patients (52.5%) had ≥cT3 disease and 55% received neoadjuvant chemotherapy (NAC). Median percent of plasmacytoid histology was 20% (IQR 5-80%) with 6 (14%), 2 (5%), 5 (11%), 16 (36%), and 15 (34%) being pT0, pT1, pT2, pT3, and pT4, respectively. Of the patients with pT3 disease, 6 were pT3a with a median 78% (IQR 39-82%) PFIr while 10 were pT3b with an associated median PFIr of 56% (42-63%). In total, 14 (32%) patients had positive soft tissue surgical margin, with 11 (79%) being of PUC histology and ten patients with a positive ureteral margin, 80% of which consisted of PUC histology. A total of 97 lymph nodes removed were positive for malignancy with 51.5% demonstrating PUC and 48.5% CUC histology. Univariate analysis confirmed an increasing percentage of PUC histology portended a worse OS (HR 3.27, 95% CI 1.22-8.73, p = 0.018). Additionally, we calculated Pearson’s correlation coefficient for percent of plasmacytoid histology with pathologic tumor stage (r = 0.468, p = &lt; 0.001), soft tissue margin (r = 0.283, p = 0.031), and lymph node density (r = 0.264, p = 0.138). Finally, KM analysis for histologic subtype (PUC vs CUC) at positive margin or positive lymph did not affect OS (p &gt; 0.05), likely a product of our small numbers. Conclusions: The plasmacytoid component of bladder cancer is more likely to spread through direct extension along tissue planes to the surrounding soft tissue and ureters rather than through lymphatics. Also, given the discohesive nature of PUC histology, gross peri-vesical extension may be an inadequate method of sub-stratifying stage pT3 disease.

Abstract 3132: Highly expressed wnt10b is associated with immune repression status in recurrent melanoma patients with positive sentinel lymph nodes

Abstract Background: The sentinel lymph node (SLN) is the first immune recognition site during tumor development, making it critically important in the shaping of subsequent adaptive immune responses against tumors. Melanoma patients with a single microscopically positive SLNs are classified as stage III despite the fact that there is significant variation in disease recurrence. Understanding of why there is such a wide disparity in outcomes among these patients may direct us to find a better treatment strategy to reduce recurrence and increase survival. Our previous studies have shown that expression of Wnt10b in the SLN was significantly higher in melanoma patients with recurrence versus those without recurrence. Given the importance of Wnt signaling in the immune response to cancer and the immunosuppression status in local microenvironments in recurrent patients, we suspect that highly expressed Wnt10b may be connected to dysfunction of the immune responses in melanoma patients with recurrence. Hypothesis: Highly expressed Wnt10b represses anti-tumor immune responses and increases the likelihood of recurrence in melanoma patients. Methods: 36 retrospective SLN RNA samples from node-positive melanoma patients were used. 18 were obtained from recurrent melanoma patients and 18 were from melanoma patients without recurrence. We performed RT-PCR to confirm the highly expressed Wnt10b in melanoma patients with recurrence and compared the expression of Wnt pathway receptors FZD3 and LRP5 between the recurrent and non-recurrent melanoma patients. Immunohistochemistry (IHC) was used to check the expression of Wnt10b, CD8; a cell surface marker of cytotoxic T cells; and FoxP3; a transcription factor mostly found in T cells associated with immune suppression; as well as the melanoma cell marker SOX10. CyTOF (Cytometry by Time of Flight) was used to compare the immunophynotype of SLN cells from patients that are projected to have higher chance of recurrence versus those who have lower chance of recurrence. Results: Wnt receptors, FZD3 and LRP5 were overexpressed in recurrent patients versus the patients without recurrence. After the data were adjusted for melanoma tumor burden, the ratio of CD8:FoxP3 was significantly lower in recurrent melanoma patients who had higher Wnt10b expression versus those without recurrence who had lower Wnt10 levels. Patients who are projected to have higher chance of recurrence have lower CD8 Naïve T cells than those who have lower chance of recurrence. Conclusions: Highly expressed Wnt10b in recurrent melanoma patients is associated with immune suppression status in the SLN. Further research is ongoing to define the mechanisms by which Wnt10b suppresses the immune responses in the SLN. These findings may lead to the development of novel therapeutic targets and strategies. Citation Format: Austin McMasters, Hong Li, Hongying Hao, Kelly M. McMasters. Highly expressed wnt10b is associated with immune repression status in recurrent melanoma patients with positive sentinel lymph nodes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3132.

Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy for patients with stage III-N2M0 non-small cell lung cancer (NSCLC): A population-based study.

8503 Background: Stage III-N2 non-small cell lung cancer (NSCLC) is a heterogeneous disease with controversial management options. Induction therapy as part of multimodal treatment is the standard of care for Stage III-N2 NSCLC. We aim to investigate the effect of adding radiotherapy to neoadjuvant chemotherapy on survival outcomes. Methods: All adult NSCLC patients diagnosed between 2004 and 2015 were identified in the Surveillance, Epidemiology, and End Results (SEER) database using ICD-O-3 histologic type coding. Inclusion criteria involved stage III NSCLC patients with ipsilateral lymph node involvement (N2), of any T stage, and with no known distant metastasis (M0). Our main sub-cohorts were patients who either underwent chemoradiotherapy (CRT) or chemotherapy (CT) in neoadjuvant settings. Our primary outcomes were overall survival (OS) and cancer-specific survival (CSS) in months. Cox proportional hazards model was used to analyze the effect of each treatment modality on OS and CSS in univariate and multivariate fashions. Multivariate analysis was adjusted for age, sex, marital status, T stage, resected lymph node status, tumor histology, primary site, laterality, and surgical procedure. Inverse probability treatment weighting (IPTW) was applied to create weighted samples based on study covariates. Results: Our analysis included 1175 patients; 799 (68.0%) underwent neoadjuvant CRT and 376 (32.0%) underwent neoadjuvant CT. Sample median age was 63 (IQR:56-69) years. T2 stage was the most prevalent (N =561, 47.7%), followed by T4 (N=243, 20.7%), T1 (N=228, 19.4%), and T3 (N=143, 12.2%). The main tumor histology was non-squamous cell carcinoma in 773 (65.8%) patients. The upper lobe was the most common primary tumor site (N =788, 67.1%). Patients underwent lobectomy (N=917, 78.0%), pneumonectomy (N=184, 15.7%), or sub-lobar resection (N=69, 5.9%). Adding radiotherapy to chemotherapy showed a slightly higher median OS than chemotherapy alone in neoadjuvant settings (51 vs. 47 months, respectively), and a higher median CSS (75 vs. 59 months, respectively). However, these differences were not statistically significant for OS or CSS (HR = 1.08, 95% CI: 0.91-1.28 and HR = 1.04, 95% CI: 0.89-1.21, respectively). After adjustment, age, T3-T4 stage, non-squamous histology, lower lobe primary site, positive resected lymph nodes, and pneumonectomy were all significant independent predictors for worse OS and CSS. IPTW analysis showed no remarkable survival advantage for CRT patients (HR = 1.15, 95% CI: 0.95-1.40 and HR= 1.12, 95% CI: 0.90-1.39) for OS and CSS, respectively. Conclusions: Adding radiotherapy to neoadjuvant CT did not result in significant survival benefits. Multiple prognostic factors should be taken into consideration when identifying the optimal choice and sequence of multimodal treatment for stage III-N2M0 NSCLC patients.

Validation of international predictive nomograms for non-sentinel lymph node metastases in Hong Kong breast cancer patients with positive sentinel lymph nodes

Validation of international predictive nomograms for non-sentinel lymph node metastases in Hong Kong breast cancer patients with positive sentinel lymph nodes

Camrelizumab combined with TIP (paclitaxel+cisplatin+ifosfamide) as neoadjuvant treatment of locally advanced penile cancer before lymphadenectomy: An exploratory, phase Ⅱ study.

TPS5093 Background: Penile squamous cell carcinoma (PSCC) is a highly aggressive disease that accounts for 95% of penile cancers and is characterized by a high risk of early locoregional spread and morbidity with subsequent potential for distant dissemination. The lymph node invasion is one of the most important factor that affects the prognosis of PSCC. Penile cancer patients with uninvolved inguinal lymph nodes had a 5-year survival rate of 66% compared with 27% for those with involvement, and penile cancer with the pelvic lymph node involvement have a worse 5-year survival rate that is typically less than 10%. Therefore, this study aims to reduce small lesions to reach the radical lymphadenectomy by camrelizumab combined with TIP in the neoadjuvant treatment of PSCC. Methods: In this single-arm, prospective, phase Ⅱ study, 34 patients with histological or cytological diagnosis of locally advanced PSCC (TX, N2-N3, M0), ECOG performance score of 0-1, planned to be recruited. Enrolled patients with inguinal and/or pelvic lymph node metastasis (positive percutaneous lymph node biopsy) after primary tumor resection of penile cancer were treated with combined therapy including camrelizumab (200 mg, iv, Q3W), paclitaxel (175 mg/m2, iv, Q3W), cisplatin (25 mg/m2, iv, Q3W) and ifosfamide (1200 mg/m2, iv, Q3W) for a total of 4 cycles. The primary endpoint is the rate of pathologic complete response (pCR). Secondary endpoints are event-free survival, overall survival, objective response rate, disease control rate and safety. On the basis of a threshold pCR rate of 13.6%, targeting an expected pCR of 34% and assuming 12 months follow-up, 80% power and a one-sided α = 0.05, this design requires 34 evaluable patients to be accrued over 3 years. Clinical trial information: ChiECRCT20210503.

The real-world experience of adjuvant docetaxel and cyclophosphamide (TC) chemotherapy in HER-2 negative breast cancer.

538 Background: Adjuvant chemotherapy in breast cancer (BC) substantially improves overall survival (OS) and the risk of recurrence. The short and long-term side effects of anthracycline, and its modest benefits in the adjuvant setting, led to controversy about its role in comparison with TC. We aim to compare the OS of TC with anthracycline-based regimens in Ontario, the most populous province in Canada. Methods: We conducted a retrospective population-based cohort study using the Institute for Clinical Evaluative Sciences (ICES) database, involving females with stage I-III BC HER2-negative. Patients were treated with adjuvant chemotherapy between January 2009 to December 2017. The anthracycline regimens for comparison were as follows, FEC-D: Fluorouracil, Epirubicin, Cyclophosphamide, followed by Docetaxel; and ACT: Doxorubicin, Cyclophosphamide, followed by Docetaxel or Paclitaxel. Exclusion criteria included missing baseline characteristics, a prior history of malignancy or chemotherapy starting more than 120 days from breast surgery. The end of follow-up was March 31st, 2018. Adjusted analyses to compare OS by positive axillary lymph nodes (LN) and chemotherapy regimens were conducted with Cox proportional hazards models. Results: Of a total 10634 female patients with BC, 60% were ≥ 50 years-old, with 19.6% stage I, 61.1% stage II, and 19.3% stage III and 7130 (67%) women were classified as ER+ and 2379 (22.4%) as ER-. Among 5764 (54.2%) patients with positive LN, 4300 (40.4%) had LN 1-3 and 1464 (13.8%) had LN ≥ 4. There were 4945 (46.5%) high-grade cases. There were 2487 (23.5%) patients treated with TC, 2981 (28%) with ACT, and 5166 (48.5%) with FEC-D. With a median follow-up of 5.5 years, the OS comparison for the entire study population showed hazard ratio (HR) of TC vs ACT was 1.47 (95% CI 1.14 – 1.90), p = 0.0027 and TC vs FEC-D HR was 1.48 (95% CI 1.18 – 1.86), p = 0.0007. For ER+ patients treated with TC, the OS comparison of LN 1-3 and LN ≥ 4 vs. LN 0 showed HR 1.34 (95% CI 0.81 – 2.21), p = 0.26, and HR 4.29 (95% CI 2.09 – 8.79), p &lt; 0.0001, respectively. For ER+ LN 0 patients, the OS HR of TC vs. ACT was 1.15 (95% CI 0.58 – 2.35), p = 0.67, and TC vs. FEC-D HR was 1.38 (95% CI 0.81 – 2.33), p = 0.23. For ER- patients treated with TC, the OS comparison of LN 1-3 and LN ≥ 4 vs. LN 0 showed HR 1.12 (95% CI 0.42 – 3.01), p = 0.82 and HR 4.41 (95% CI 1.33 – 14.59), p = 0.015, respectively. For ER- LN 0 patients, the OS HR for TC vs. ACT was 2.04 (95% CI 1.09 – 3.81), p = 0.025, and TC vs. FEC-D HR was 2.05 (95% CI 1.08 – 3.90), p = 0.028. Conclusions: Patients treated with adjuvant TC who had four or more axillary LN had significantly lower OS when compared to patients with LN 0. For women with ER- disease, TC demonstrated a significant unfavourable survival outcome when compared to anthracycline-based treatments.

Craniocaudal nodal length (CCNL) as a risk-factor for relapse in stage I non-seminomatous germ cell tumors (NSGCT).

e17011 Background: Lymphovascular invasion and embryonal carcinoma predominant (ECP) subtype are the only consistent factors predictive of relapse on active surveillance (AS) in Stage I NSGCT. Current practice guidelines define stage I disease by axial dimensions only, despite routine coronal reformations of axial CT images permitting CCNL measurement. CCNL was previously reported to be associated with increased risk of relapse in stage I NSGCT, independent of other risk factors (Howard et al, 2014). We sought to validate this finding through time-to-event (TTE) analyses in a larger, independent cohort. Methods: Patients with NSGCT who had undergone orchiectomy between 2/1/10 and 10/31/2017 and had baseline CT imaging performed within 90 days of orchiectomy were included. CCNL was measured using the largest lymph node by axial dimensions, with nodal morphological descriptors recorded. Median CCNL (17mm) was rounded to the nearest 5mm (15mm) and dichotomized into &lt;15mm or &gt; 15mm, deemed the most clinically translatable landmark. TTE was a composite of either relapse on AS, a positive primary retroperitoneal lymph node dissection (PRPLND), or relapse after negative PRPLND. TTE was estimated using Kaplan-Meier method, with time calculated from date of orchiectomy to date of event or censoring at last follow-up. Results: 134 stage I NSGCT patients were included, 64 (48%) with stage IA and 70 (52%) with stage IB. Median age at diagnosis was 30 years (range 18 to 34). ECP histology was seen in 82 (61%) patients. Median CCNL was 17mm (range 5 to 34) and 71 patients (53%) had a CCNL &gt; 15mm. Presence of fatty hilum and suspicious morphology were observed in 86 (66%) and 11 patients (8%) respectively. CCNL did not differ by stage at diagnosis (Wilcoxon p = 0.26) or ECP histology (Wilcoxon p = 0.95). PRPLND was performed in 7 of 64 stage IA (11%) and 45 of 70 stage IB (64%) patients. Twenty-six patients relapsed on AS, 9 had positive PRPLND histology and 3 with a negative PRPLND later relapsed. All 38 events occurred in the first year after orchiectomy except for relapse on AS in three stage IA patients at 1.2, 2.8 and 4.0 years. Median follow-up time is 5.0 years (range 1.5 months to 10 years). The one-year event-free rate was 72.7% (95% CI: 64.0, 79.6). TTE differed significantly by stage at diagnosis and did not differ significantly by ECP histology, CCNL (&gt; 15mm versus ≤15mm), presence of fatty hilum, or presence of suspicious morphology (all p &gt; 0.05). In a stratified analysis, event rate did not differ by CCNL &gt; 15mm versus ≤15mm within stage IA or IB patients (p = 0.58 and 0.60, respectively). Conclusions: Using TTE analyses in a larger, contemporary patient cohort, CCLN was not associated with increased risk of relapse in stage I NSGCT and does not lend support to its addition to staging or risk prediction models. The association between CCNL and relapse risk in stage I seminoma is currently being analyzed.

Comparing single or dual tracing modality on sentinel lymph node biopsy from patients who plan to omitting axillary lymph node dissection referring to the criteria of Z0011 trial: a retrospective study.

Axillary lymph node dissection (ALND) can be omitted in the part of the breast-conserving patients with positive sentinel lymph nodes (SLNs) since Z0011 trial has presented. Nevertheless, to date, no studies revealed the influence of different tracing modalities (single tracer versus dual tracers) for sentinel lymph node biopsy (SLNB) on axillary management referring to Z0011 trial criteria. This study aimed to assess whether different tracing modalities of SLNB have impact on axillary management referring to Z0011 trial criteria. The clinical data of breast-conserving patients who underwent SLNB guided by combination of methylene blue (MB) and indocyanine green(ICG) were retrospectively analyzed in our center. The numbers of metastatic (positive) SLNs guided by the single tracer and the dual tracer were compared by self-control study. 127 patients with 1-2 metastatic SLNs dyed by MB [(recorded as MB(+))]were retrieved from our database between 2016 and 2020. In these cases, 53 patients contained 86 SLNs, which were ICG staining but MB negative staining (recorded as ICG(+)/MB(-)). In addition, 16 patients contained 20 metastatic SLNs with ICG(+)/MB(-). There were six patients finally excluded patients (6/127, 4.7%) who initially met the criteria of Z0011 trial, because the further detection of ICG(+)/MB(-) SLNs led the total numbers of positive SLNs over two. The difference was statistically significant. Single tracing modality may underestimate the positive SLN numbers compared to dual tracing modality. Different tracing modalities of SLNB will significantly affect Axillary management referring to Z0011 trial criteria.

Prevalence of Positive Level IIb Lymph Nodes in Tongue Carcinoma: Experience From a Tertiary Care Center in North India.

IntroductionComplications during and after dissection of level IIb lymph nodes include spinal accessory nerve (SAN) dysfunction, which results in the limitation of shoulder movements and, thus, hurts the quality of life. The current study aims to know the occurrence of level IIb lymph node positivity in tongue carcinoma.MethodsThis cross-sectional study was conducted from January 2019 to December 2019 in a tertiary care center in North India. Adult cases with primary ulcer-proliferative growth over the lateral border of the tongue were included in the study. The level IIb lymph node positivity from the postoperative histopathology report was the primary outcome measure of this study. To investigate the potential association of tumor size on level IIb lymph node positivity, we compared the maximum tumor dimensions among the level IIb lymph node-positive and -negative groups. In addition, to analyze the impact of the tumor's invasive nature on level IIb lymph node positivity, we compared the depth of invasion and proportion of cases with muscle involvement among the level IIb lymph node-positive and -negative groups. Lastly, to investigate their concurrent occurrences, we compared the number of level IIb lymph node-positive cases among the level IIa lymph node-positive and -negative groups.ResultsA total of 39 patients fulfilling the inclusion criteria were included in the study. Only six had positive level-IIb lymph nodes. No significant associations of tumor size, invasion depth, muscle invasion, or involvement of level IIa lymph nodes with the positivity of level IIb lymph nodes were found. However, only three were level IIb lymph node-positive in 28 level IIa lymph node-negative cases.ConclusionConsidering the low risk of isolated level IIb lymph node positivity in level IIa lymph node-negative cases, the dissection of level IIb nodes could be omitted during the surgical excision of the tumor. However, radiological investigations detecting metabolic activity should be used in the preoperative period and postoperative follow-up to detect early lymph node involvement and disease recurrence.

Lymph-Venous Anastomosis for Breast Cancer-Related Lymphoedema after Docetaxel-Based Chemotherapy.

Docetaxel-based chemotherapy, which is administered before or after axillary lymph node dissection (ALND) in breast cancer patients with positive axillary lymph nodes, is reported as an independent risk factor for development of breast cancer-related lymphoedema (BCRL). Severe hardening of the soft tissue, which is a typical manifestation of BCRL with a history of docetaxel-based chemotherapy, has been considered a contraindication for lymph-venous anastomosis (LVA). This study aimed to evaluate the efficacy of LVA for BCRL with a history of the use of docetaxel. Twenty-six consecutive BCRL patients who underwent LVA were reviewed retrospectively. All patients underwent ALND. Amongst 23 patients who had chemotherapy for breast cancer, docetaxel-based chemotherapy was administered in 12 patients. The postoperative change of the limb circumferences and the improvement of subjective symptoms were assessed. Overall, patients showed improvements of the limb circumferences at the wrist, the elbow, and 5 cm above and below the elbow. There were no statistical differences of the postoperative changes of the circumferences between the docetaxel-administered and non-administered groups (0.25% vs. 2.8% at 5 cm above the elbow (p = 0.23), −0.4% vs. 0.7% at 5 cm below the elbow (p = 0.56), and 2.5% vs. 2.5 % at the wrist (p = 0.82)). LVA is comparably effective for lymphedematous patients who had undergone docetaxel-based chemotherapy before or after ALND.

Does ultrasound evaluation of the axilla increase the rate of axillary lymph node dissection in early stage clinically node negative breast cancer patients?

BackgroundManagement and axillary staging of breast cancer has become less invasive and more conservative, over the decades. Considering Z011, axillary lymph node dissection (ALND) can be avoided in T1-2 N0-1 breast cancers with one or two positive sentinel lymph nodes (SLNs), if they are candidates for breast conserving surgery and radiotherapy. The aim of this study was to recognize if pre-operative axillary US evaluation in early-stage breast cancer could lead to more ALND in post Z011 era.Method463 breast cancer patients were evaluated. 368 early-stage breast cancer patients (T1-2 N0) were included. We did not perform axillary US in early stage clinically node negative patients; however, 97 patients had axillary US prior to our visit. If axillary US could detect more than two suspicious LNs, US guided biopsy was performed. The remaining clinically node negative patients underwent upfront SLNB. ALND was performed if more than two SLNs were metastatic, or US-guided ALN biopsy proved metastatic involvement.Results97 patients had axillary US evaluation before the surgery. 67 patients (69.2%) did not have any suspicious US detected axillary LNs, 17 patients (17.5%) had one, 7 patients (7.2%) had two, and 6 patients (6.2%) had more than two suspicious LNs according to their axillary US evaluation. Those with more than two suspicious LNs underwent ALN US-guided biopsy. Metastatic involvement of the LNs was proved in all of them and they underwent upfront ALND. ALND revealed more than 2 metastatic LNs in 2/6 patients (33.3%). 91 patients who were evaluated by axillary US, had less than two US detected suspicious LNs and underwent SLNB. Amongst 24 patients with one or two US detected suspicious LNs, 1/24 patient had more than two positive SLNs and underwent ALND. In this group 15.6% underwent ALND and 5.2% of them were unnecessary according to the recent guidelines. Axillary US had a false positive rate of 36.6%. The sensitivity of axillary US in distinguishing patients with more than two suspicious LNs in clinically node negative patients was 25%. In the second group (without pre-operative axillary US evaluation), SLNB was performed. 204/272 patients (75%) did not have LN metastasis. 54/272 patients (19.9%) had one or two metastatic SLNs and according to Z011, ALND was omitted. 5.1% had more than two metastatic SLNs and underwent ALND.ConclusionUS evaluation of the axilla in early stage, clinically node negative breast cancer patients, is not sensitive enough to recognize more than two metastatic ALNs. It leads to more unnecessary ALND. Despite the small number of patients in this study, these results question the rationale of axillary US guided biopsy in low burden (less than two) suspicious LNs. looking for an imaging modality with a higher sensitivity in detecting the Burdon of axillary metastatic involvement is mandatory.

A Predictive Model for Nonsentinel Node Status after Sentinel Lymph Node Biopsy in Sentinel Lymph Node-Positive Chinese Women with Early Breast Cancer.

Background Axial lymph node dissection (ALND) is needed in patients with positive sentinel lymph node (SLN). ALND is easy to cause upper limb edema. Therefore, accurate prediction of nonsentinel lymph nodes (non-SLN) which may not need ALND can avoid excessive dissection and reduce complications. We constructed a new prognostic model to predict the non-SLN metastasis of Chinese breast cancer patients. Methods We enrolled 736 patients who underwent sentinel lymph node biopsy (SLNB); 228 (30.98%) were diagnosed with SLNB metastasis which was determined by intraoperative pathological detection and further accepted ALND. We constructed a prediction model by univariate analysis, multivariate analysis, “R” language, and binary logistic regression in the abovementioned 228 patients and verified this prediction model in 60 patients. Results Based on univariate analysis using α = 0.05 as the significance level for type I error, we found that age (P=0.045), tumor size (P=0.006), multifocality (P=0.011), lymphovascular invasion (P=0.003), positive SLN number (P=0.009), and negative SLN number (P=0.034) were statistically significant. Age was excluded in multivariate analysis, and we constructed a predictive equation to assess the risk of non-SLN metastasis: Logit(P)=Ln(P/1 − P)=0.267∗a+1.443∗b+1.078∗c+0.471∗d − 0.618∗e − 2.541 (where “a” represents tumor size, “b” represents multifocality, “c” represents lymphovascular invasion, “d” represents the number of metastasis of SLN, and “e” represents the number of SLNs without metastasis). AUCs for the training group and validation group were 0.715 and 0.744, respectively. When setting the risk value below 22.3%, as per the prediction equation's low-risk interval, our model predicted that about 4% of patients could avoid ALND. Conclusions This study established a model which demonstrated good prognostic performance in assessing the risk of non-SLN metastasis in Chinese patients with positive SLNs.

Clinical characteristics of patients with collecting duct carcinoma.

297 Background: Collecting duct carcinoma (CDC) is traditionally classified as a rare renal cell carcinoma. It comprised less than 2% of all renal cell carcinoma but presented a highly aggressive clinical course1. The natural history of CDC was merely described in small-sample retrospective studies because of its low incidence. Methods: We retrospectively collected clinicopathological data of patients (pts) diagnosed with CDC in our center from 2006 to the present. Histological diagnoses of all patients with CDC were confirmed by two senior urologic pathologists. Results: CDC was found in 58 pts (60% males and 22% over 65 years old). Most started with hematuria, low back pain, or systemic symptoms; 7 pts (12%) had no clinical symptoms. 67% pts underwent partial or radical resection of the kidney. 39.7% pts had distant metastases at diagnosis. Among the 35 pts with no distant metastasis at diagnosis, 18 (51%) had positive regional lymph nodes, 22 (63%) had locally advanced T stage (T3 or T4), and 18 (51%) were G3/4 by Fuhrman or WHO/ISUP. For pts undergoing radical nephrectomy, the median disease-free survival (DFS) was 6.3 mos (95%CI: 0.2, 12.4), and the median OS was 22.5 mos (95%CI: 16.6, 28.4), which were significantly related to T stage (P = 0.033 and 0.001). For pts after metastasis (56 cases), the most common sites of recurrence and metastasis were lymph nodes (55%), lung (46%), bone (36%), liver (16%), adrenal glands (7%), and local recurrence (20%). The median OS after metastasis was 11.3 mos (95%CI: 9.5, 13.0). Among the locally advanced or metastatic pts, 33 received gemcitabine + cisplatin combined with sorafenib as the first-line therapy. There were 8 PR and 17 SD. The ORR was 24.2%, DCR was 75.8%, and median PFS was 6.1 mos (95% CI: 4.7, 7.5). The median OS was 12.1 mos (95% CI: 8.6, 15.5). In 2 pts receiving anti-PD-1 monoclonal antibody combined with axitinib, 1 case had PR and 1 obtained SD with tumor shrinking. They are still under follow-up. Conclusions: CDC is prone to be diagnosed at a late stage and develop metastases. There is currently no standard treatment for metastatic patients; gemcitabine + cisplatin combined with sorafenib can be tried in the first-line setting. Anti-PD-1 plus axitinib showed promising efficacy in cases of CDC, and a larger sample is needed for verification.

Urothelial carcinoma with sarcomatoid variant: A preliminary study of clinical and pathological features.

571 Background: Muscle-invasive urothelial carcinoma (UC) with sarcomatoid variant (SV) (SV-UC) occurs in 0.1-0.3% of UC cases, and has been related with worse prognosis. Due to rarity of SV-UC, there are still limited evidences about the predictive role of sarcomatoid differentiation and no agents has been tested for SV-UC. We aim to investigate clinical and pathology features of SV-UC in a high grade UC (HG-UC) patients (pts) cohort. Methods: A retrospective analysis was performed on pts with HG-UC referring to our center between December 2012 and June 2021. Pts were reviewed for availability of histological tumor samples to evaluate the presence of SV. The expression of PD-L1 was evaluated in SV-UC sample by immunohistochemistry (IHC) using Ventana (SP263) assay. An IHC expression &gt; 5% was considered positive. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared with the log-rank test. The Chi-Square test, t-test or Wilcoxon-Mann-Whitney test were used to assess difference between the groups as appropriate. Results: A cohort of 73 HG-UC pts were analyzed and a total of 6 SV-UC has been identified (8.2%). Two cases (2.7%) presented both SV and rhabdoid features. The median age at diagnosis was 69 years (54-81). SV-UC occurs equally in male and female (50%) vs 9% of affected female in HG-UC group (p = 0.02). Of four patients experiencing a metastatic disease (67%), two were metastatic at diagnosis (33%). One patient had an upper tract UC (17%), while remaining samples originated from bladder. Of note, in 4/6 of pts (67%) a squamous histology was reported (vs 10.5% in HG-UC group; p = 0.1). SV was found in &gt; 30% of tissue sample in 4/6 cases, 15% in one case, undefined in the remaining one. The PD-L1 expression in SV-UC tissues was &gt; 50% in 5/6 of cases (83%), negative in the remaining one ( &lt; 5%). All pts in SV-UC group had advanced stage of desease: 4/6 had pT3 stage (67%), 2/6 had pT4 stage (33%) and 4/6 had positive loco-regional lymph nodes. All SV-UC pts had local recurrence. Four pts with metastatic desease were treated with chemotherapy, and 3 received also immunotherapy. The majority of treated pts (2/3) achieved progression as best first line response (22% in HG-UC). With a median follow up of 33 months (range 2-110), median PFS was 1.3 and 6.3 months (HR 0.51, 95%CI 0.11-2.17, P = 0.36) and median OS was 8.9 vs 20.3 months in SV-UC and HG-UC group, respectively (HR 0.51, 95%CI 0.11-2.17, P = 0.36). Conclusions: This analysis explored incidence and clinico-pathologic features of SV in pts with HG-UC, identifying an often underestimated subpopulation. Compared to HG-UC, SV-UC appears to be associated with lower M:F ratio, squamous histology, advanced disease and higher PD-L1 expression. Our initial results confirmed an association with shorter PFS and OS. The major limitation of our series is the small number of cases, a larger study is already planned.

Abstract PD7-08: Less is not necessarily more: A propensity matched national analysis on effect and outcome of sentinel lymph node biopsy omission

Abstract Background: Routine sentinel lymph node biopsy (SLNB) has been recommended against by Choosing Wisely© Foundation due to its low value in clinical node negative, hormone receptor positive breast cancer patients age≥70 years old. We used the National Cancer Database (NCDB) to examine the effect of SLNB omission and outcomes in this population. We hypothesized that SLNB would be beneficial in this population.Methods: The National Cancer Database was queried for women diagnosed with primary unilateral invasive clinical stage T1N0M0 hormone receptor positive, HER-2 negative breast cancer from 2012-2017. Patients age ≥ 70 years old with Charlson Score ≥1 who underwent partial mastectomy and received hormonal therapy were included in the study cohort. Patients received neoadjuvant therapy or underwent upfront axillary lymph node dissection (ALND) were excluded. A 1:3 propensity match with replacement was performed to compare SLNB omission vs. SLNB group controlling age, race, comorbidities, insurance and facility. Overall survival was analyzed using stratified multivariable Cox proportional hazard regression analysis.Results: Of 14,150 patients, 1,928 (13.6%) omitted SLNB and 12,222 (86.4%) underwent SLNB, including 1,545/12,222 (12.6%) who proceeded to ALND. Central portion tumor location (OR=1.77, P=0.001), clinical T1c (OR= 2.49, P&amp;lt;0.001) and lymph-vascular invasion (OR=7.46, P&amp;lt;0.001) were significant associated with positive pathological lymph node involvement in SLNB group. Among the 1,397 patients of positive nodal status with SLNB, 87.7% received radiation therapy and 19.3% received chemotherapy. Propensity matching reduced bias between the groups, generating 1,903 SLNB omission and 5,703 SLNB patients for analysis. After match, the SLNB omission group was less likely to receive chemotherapy (1.1% vs. 3.0%, p&amp;lt;0.001) or radiation therapy (28.9% vs. 60.8%, p&amp;lt;0.001). Omitting SLNB was associated with inferior overall survival (3-year 83.7% vs. 90.6%, 5-year 66.4% vs. 76.1%, p&amp;lt;0.001). Omitting SLNB was also associated with inferior survival in multivariate cox regression (HR=1.64, p&amp;lt;0.001). Chemotherapy (OR=0.51, p=0.020) and radiation therapy (OR=0.85, P=0.007) were associated with superior overall survival.Conclusions: SLNB remains to be of importance in cT1N0M0 HR+HER2- patients of age 70 years. Pathologic staging affects decisions on adjuvant treatment and SLNB omission is associated with inferior survival. In this population, SLNB might need to be re-implemented, especially in patients with high likelihood of nodal involvement. Citation Format: Lifen Cao, Megan E Miller, Luke D Rothermel, Alberto J Montero, Christopher W Towe, Robert Shenk. Less is not necessarily more: A propensity matched national analysis on effect and outcome of sentinel lymph node biopsy omission [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD7-08.

Abstract P1-01-17: Machine learning-based DNA methylation classifiers to predict pathologic nodal stage in breast cancer patients with clinically node positive disease

Abstract Introduction: Axillary lymph node dissection (ALND) has no apparent oncologic benefit for breast cancer patients with clinically negative axillae and 1-2 positive sentinel lymph nodes so omission has been considered appropriate for this patient cohort. For patients with clinically positive nodes who are not treated with neoadjuvant chemotherapy (NAC), ALND is routinely recommended. Yet, at ALND, up to 40-57% of patients are found to have ≤ 3 positive nodes (pN1). No accurate method exists for identifying patients with minimal nodal disease who can potentially be spared the morbidity of ALND. DNA methylation (DNAm) has emerged as a potential tool for creating different classifiers to stratify cancer patients using artificial intelligence methods, such as machine learning. This study employed machine learning algorithms to create DNAm-based classifiers that efficiently stratify patients with clinically positive nodes to pN1 vs &amp;gt;pN1 disease. Methodology: We used publically available data from The Cancer Genome Atlas (TCGA) of breast cancer patients (n=1,006). We curated the cohort to select patients with hormone receptor-positive and HER2 negative invasive ductal carcinoma who were not treated with NAC. We only included patients who had undergone an ALND and had available DNAm (HM450 BeadChip array) data (n=58). Two Random Forest methodologies were used to obtain different combinations of DNAm features with high accuracy in stratifying pN1 and &amp;gt;pN1 patients. The most efficient combination of CpG sites was selected according to the Area Under the Curve (AUC) of each combination. Results: First, the differentially methylated sites (DMS, n=218) between pN1 and &amp;gt;pN1 patients were computed. Using all DMS displayed a good predictive potential for the selection of pN1 patients (AUC=0.88). Three different panels were obtained, containing 20 (P20), 15 (P15), and 13 (P13) genomic regions per panel. All three signatures displayed an excellent performance stratifying pN1 from &amp;gt;pN1 patients (AUCP20=0.98, AUCP15=0.98, and AUCP13=0.97). Furthermore, these epigenetic signatures showed a higher discriminative potential than clinical and pathological variables, such as the location of the tumor, tumor size, age, and tumor grade. Discussion: Due to the lack of data, ALND is still recommended for patients with clinically node positive disease. However, over half of patients with clinically positive nodes have minimal (pN1) nodal disease at surgery and could theoretically avoid ALND. We have designed three artificial intelligence DNAm-based panels (P20, P15, and P13) which efficiently stratify pN1 from &amp;gt;pN1 patients. These classifiers are more accurate than clinical and pathological variables for selecting patients with a low number of positive nodes. Furthermore, our method employs a small number of genomic regions (13 to 20), facilitating the use of PCR-based assays, such as quantitative Methylation Specific PCR (qMSP), which decreases cost compared to high-throughput technology, and increases availability and accessibility of this predictive tool. Citation Format: Maggie L. DiNome, Miguel Ensenyat-Mendez, Javier I.J. Orozco, Dennis Rünger, Jennifer L. Baker, Joanne B. Weidhaas, Diego M. Marzese. Machine learning-based DNA methylation classifiers to predict pathologic nodal stage in breast cancer patients with clinically node positive disease [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-01-17.

Abstract ES8-2: Can radiation replace ALND after positive SLNB?

Abstract Growing recognition of the adverse impact of lymphedema on quality of life of survivors of breast cancer has motivated efforts to identify alternatives to axillary lymph node dissection. In some patients who have positive sentinel lymph nodes, radiation therapy may provide a more tolerable alternative to ALND without compromising disease control. This session will focus on the results of the key randomized trials directly evaluating this question: AMAROS and OTOASOR, as well as the implications of other trials that can help to identify patients in whom de-escalation of axillary surgery appears safe. Citation Format: R Jagsi. Can radiation replace ALND after positive SLNB? [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES8-2.

Abstract P2-09-16: Clinicopatological features and outcome of breast cancer in CHEK2 germline mutation carriers

Abstract Background: Carriers of CHEK2 germline mutations are at moderately increased (20-40%), lifetime risk for developing breast cancer (BC), in part depending on specific family history and mutation type and location. CHEK2 mutation associated BC is commonly associated with positive estrogen receptor(ER) tumor subtype, but other tumor features are less evident. Long term follow up and outcome of patients with CHEK2 -associated BC has not been reported. The clinical and tumoral features as well as and clinical outcome of a consecutive series of 57 BC patients (63 primary tumors) harboring pathogenic CHEK2 mutation is presented. Methods: Following IRB approval, hospital records from 3 major cancer centers in Israel were reviewed to identify female CHEK2 pathogenic/likely pathogenic sequence variant (P/LPSV) carriers who were diagnosed with BC between 2001-2021.Relevant clinical features, tumor data, treatment details and outcome were retrieved and. Mann-Whitney U-test was performed for continuous variables and descriptive statistics were used for non-continuous variables.Results:104 BC cases with documented CHEK2 sequence variant were obtained. 57 were carriers of CHEK2germline P/LPSV, and 63 primary tumors were diagnosed in these participants. Median age at diagnosis was 50 years (mean 51, range 31-73) and median follow up time of 23.5 months (mean 47,range 1-228). Six of 57 [10.5%] were diagnosed with synchronous bilateral tumors, and 6 [10.5%]with multifocal ipsilateral tumors. Twenty-three (41%) of the invasive tumors had positive regional lymph nodes at diagnosis and median tumor size was 1.2cm (mean 1.9, range 0.3-11.3cm). Seventy seven percent were invasive ducal carcinoma, 8% were invasive lobular, 11% DCIS, and two cases -unknown histology. Fifty-seven of 63 tumors (90%) were ER positive, and only two cases were triple negative. Ten (16%)tumors were HER2 positive. Most tumors (66%) were intermediate grade, 18% - low-grade, and 16%- high-grade tumors. Eighty percent opted for breast conserving surgery and 29 received chemotherapy, all were AC-T regimen, with anti HER2 agents in HER2 positive tumors. The most common PSV were c.1100delC (17 patients) and p.S428P (17 patients). Mean age at diagnosis for these two PSVs were 47 and 57 years, respectively (p=0.00438). Seven (12%) patients developed metastatic disease during the follow up period. Conclusion: This descriptive study shows some unique features of CHEK2 associated BC: early age at diagnosis(for the c.1100delC PSV) and high percentage of ER positivity. Synchronous and multifocal tumors were common. Further long term follow up and larger detailed description is warranted in this unique population. Citation Format: Shir Schlosser, Rinat Bernstein Molho, Natalia Karminsky, Daphna Barsuk, Yael Goldberg, Eitan Friedman, Rinat Yerushalmi, Keren Drumea, Inbal Kedar, Irina Jiveliouk, Merav Akiva Ben David. Clinicopatological features and outcome of breast cancer in CHEK2 germline mutation carriers [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-09-16.