Development of a prediction model based on LASSO regression to evaluate the risk of non-sentinel lymph node metastasis in Chinese breast cancer patients with 1–2 positive sentinel lymph nodes

This study aimed to develop an intraoperative prediction model to evaluate the risk of non-sentinel lymph node (NSLN) metastasis in Chinese breast cancer patients with 1–2 positive sentinel lymph nodes (SLNs). The clinicopathologic data of 714 patients with 1–2 positive SLNs were investigated. Univariate and multivariate analyses were performed to identify the risk factors of NSLN metastasis. A new mathematical prediction model was developed based on LASSO and validated in an independent cohort of 131 patients. The area under the receiver operating characteristic curve (AUC) was used to quantify performance of the model. Patients with NSLN metastasis accounted for 37.3% (266/714) and 34.3% (45/131) of the training and validation cohorts, respectively. A LASSO regression-based prediction model was developed and included the 13 most powerful factors (age group, clinical tumour stage, histologic type, number of positive SLNs, number of negative SLNs, number of SLNs dissected, SLN metastasis ratio, ER status, PR status, HER2 status, Ki67 staining percentage, molecular subtype and P53 status). The AUCs of training and validation cohorts were 0.764 (95% CI 0.729–0.798) and 0.777 (95% CI 0.692–0.862), respectively. We presented a new prediction model with excellent clinical applicability and diagnostic performance for use by clinicians as an intraoperative clinical tool to predict risk of NSLN metastasis in Chinese breast cancer patients with 1–2 positive SLNs and make the final decisions regarding axillary lymph node dissection.

Predictors of Sentinel Lymph Node Metastasis in Postoperatively Upgraded Invasive Breast Carcinoma Patients

Sentinel lymph node (SLN) biopsy (SLNB) usually need not be simultaneously performed with breast-conserving surgery (BCS) for patients diagnosed with ductal carcinoma in situ (DCIS) by preoperative core needle biopsy (CNB), but must be performed once there is invasive carcinoma (IC) found postoperatively. This study aimed to investigate the factors contributing to SLN metastasis in underestimated IC patients with an initial diagnosis of DCIS by CNB. We retrospectively reviewed 1240 consecutive cases of DCIS by image-guided CNB from January 2010 to December 2017 and identified 316 underestimated IC cases with SLNB. Data on clinical characteristics, radiologic features, and final pathological findings were examined. Twenty-three patients (7.3%) had SLN metastasis. Multivariate analysis indicated that an IC tumor size > 0.5 cm (odds ratio: 3.11, p = 0.033) and the presence of lymphovascular invasion (odds ratio: 32.85, p < 0.0001) were independent risk predictors of SLN metastasis. In the absence of any predictors, the incidence of positive SLNs was very low (2.6%) in the total population and extremely low (1.3%) in the BCS subgroup. Therefore, omitting SLNB may be an acceptable option for patients who initially underwent BCS without risk predictors on final pathological assessment. Further prospective studies are necessary before clinical application.

Candidates of Genomic Tests in HR+/HER2- Breast Cancer Patients With 1-2 Positive Sentinel Lymph Node Without Axillary Lymph Node Dissection: Analysis From Multicentric Cohorts

BackgroundThe genomic tests such as the MammaPrint and Oncotype DX test are being gradually applied for hormone receptor positive/HER-2 negative (HR+/HER2-) breast cancer patients with up to three positive axillary lymph nodes (ALNs). The first results from RxPONDER trial suggested that Oncotype DX could be applied to patients with 1-2 positive sentinel lymph nodes (SLNs) without axillary lymph node dissection (ALND), which constituted 37.4% of the intent-to-treat population. However, there was no distinctive research on how to apply genomic tests precisely to HR+/HER2- patients with 1-2 positive SLNs without ALND. The purpose was to construct a nomogram using the multi-center retrospective data to predict precisely which HR+/HER2- candidates with 1-2 positive SLNs could be subjected to genomic tests (≤ 3 positive lymph nodes).MethodsWe conducted a retrospective analysis of 18,600 patients with stage I-III breast cancer patients treated with sentinel lymph node biopsy (SLNB) in Shandong Cancer Hospital, Fudan University Shanghai Cancer Center, and West China Hospital. The univariate and multivariate logistic regression analysis was conducted to identify the independent predictive factors of having ≤ 3 positive nodes among patients with 1-2 positive SLNs. A nomogram was developed based on variables in the final model with p&lt;0.05. Calibration of the nomogram was carried out by internal validation using the bootstrap resampling approach and was displayed using a calibration curve. The discrimination of the model was evaluated using the ROC curve.ResultsBased on the database of the three institutions, a total of 18,600 breast cancer patients were identified undergoing SLNB between May 2010 and 2020. Among the 1817 HR+/HER2- patients with 1-2 positive SLNs undergoing ALND, 84.2% harbored ≤ 3 totals metastatic ALNs. The multivariate logistic regression analysis identified imaging abnormal nodes (OR=0.197, 95%CI: 0.082-0.472), the number of positive SLNs (OR=0.351, 95%CI: 0.266-0.464), the number of negative SLNs (OR=1.639, 95%CI: 1.465-1.833), pathological tumor stage (OR=0.730, 95%CI: 0.552-0.964), and lympho-vascular invasion (OR=0.287, 95%CI: 0.222-0.398) as independent predictors for the proportion of patients with ≤ 3 total metastatic ALNs (all p&lt;0.05). These five predictors were used to create a predictive nomogram. The AUC value was 0.804 (95%CI: 0.681-0.812, p&lt;0.001). The calibration curve showed a satisfactory fit between the predictive and actual observation based on internal validation with a bootstrap resampling frequency of 1000.ConclusionThe nomogram based on the multi-centric database showed a good accuracy and could assist the oncologist in determining precisely which HR+/HER2- candidates with 1-2 positive SLNs without ALND could perform genomic tests. In the era of SLNB and precision medicine, the combined application of genomic tests and SLNB could provide patients with a better strategy of dual de-escalation management, including the de-escalation of both surgery and systemic treatment.

Predictive and Prognostic Value of BRAF and NRAS Mutation of 159 Sentinel Lymph Node Cases in Melanoma—A Retrospective Single-Institute Study

Purpose: To assess the prognostic role of sentinel lymph node status (SLN) in melanoma patients, a statistical comparison was performed with the application of already known prognostic factors, mutational occurrence of BRAF and NRAS in the primary tumor, as well as disease outcome. Methods: Our retrospective single-center study involved 159 melanoma cases, who underwent SLN biopsy. The following clinico-pathological data were collected: age, gender, location of primary tumor, Breslow thickness, ulceration degree, histological subtype, mitosis count, lymphovascular and perineural invasion, presence of tumor-infiltrating lymphocytes, regression signs, mutations of BRAF and NRAS of the primary tumors, and SLN status. Results: From the studied clinico-pathological factors, only Breslow thickness increased the risk of SLN positivity (p = 0.025) by multivariate analysis, while neither BRAF nor NRAS mutation of the primary tumor proved to be a predictor of the SLN status. While the NRAS-mutant subgroup showed the most unfavorable outcome for progression-free and distant metastasis-free survival, their rate of positive SLNs proved to be relatively lower than that of patient groups with BRAF mutation and double-wild-type phenotypes. Conclusion: Similarly to the importance of SLN positivity, NRAS mutation of the primary tumor proved to be an independent prognostic factor of progression. Therefore, despite negative SLN, this NRAS-mutant subgroup of patients still requires closer monitoring to detect disease progression.

Usefulness and Prospects of Sentinel Lymph Node Biopsy for Patients With Breast Cancer Using the Medical Imaging Projection System

BackgroundThe Medical Imaging Projection System (MIPS) projects indocyanine green (ICG) fluorescence images directly on the surgical field using a projection mapping technique. We conducted an observational study of sentinel lymph node (SLN) biopsy using the prototype MIPS; we found a high identification rate. However, the number of SLN-positive cases was small, and the sensitivity could not be evaluated. The aim of this study was to investigate the clinical usefulness of the MIPS assisted ICG fluorescence method using commercially available equipment.MethodsThis was a retrospective observational study. Patients with primary breast cancer who underwent SLN biopsy using the MIPS at Kyoto University Hospital from April to December 2020 were included in the study. The primary endpoints were the identification rate of SLNs and detection of positive SLNs by the MIPS. The secondary endpoint was the number of SLNs excised using the MIPS per patient. We also conducted a questionnaire survey focused on the utility of the MIPS; it involved doctors with an experience in using the MIPS.ResultsSeventy-nine patients (84 procedures) were included in the study. In 60 (71%) procedures, both the radioisotope (RI) method and MIPS were used. At least one SLN could be detected by the MIPS in all the procedures, with an identification rate of 100% (95% confidence interval 95.6–100%). A total of 19 (7%) positive SLNs were removed, which were identifiable by the MIPS. Among 57 patients in whom the MIPS and RI methods were used, there was no positive SLN only identified by the RI method. The results of the questionnaire survey showed that the MIPS enabled the operator and assistant to share the ICG fluorescence image in the surgical field and to communicate with each other easily.ConclusionThe current study demonstrated that the identification rate of SLNs using the MIPS was high, and the MIPS can be used for detecting positive SLNs. It was suggested that the MIPS will be useful in learning SLN biopsy procedures.

Oncological Safety of Axillary Reverse Mapping in Patients With Clinically Node-Negative Breast Cancer

Background Axillary reverse mapping (ARM) was developed to preserve the lymphatic drainage from the upper arm during sentinel lymph node (SLN) biopsy or axillary lymph node dissection (ALND). However, the oncological safety of ARM has been controversial. Methods Patients with clinically negative nodes (cN0) underwent SLN biopsy and ARM. SLNs were identified using blue dye and radioisotope, and ARM nodes were traced using the fluorescent method. Patients with positive SLN underwent the standard ALND. After surgery, they were followed up for more than three years. Results A total of 507 patients with cN0 breast cancer were enrolled between May 2009 and November 2017. SLNs were identified in 499 (98%) of 507 patients, and ARM nodes were identified in 159 (31%) patients in the SLN field. The crossover rate of SLN-ARM nodes was 28%. Among 95 patients with positive SLNs, 70 patients underwent conventional ALND. ARM nodes were identified in 65 (93%) of those patients in the ALND field. The mean number of removed ARM nodes was 7.2 (range 0–25) in patients who underwent the standard ALND. Although ARM nodes were involved in 18 of 65 patients, the involved ARM nodes were the same SLNs identified in 14 (78%) patients. Since SLN-ARM nodes should be removed, ARM nodes were involved only in 4 (5.7 %) patients after SLN biopsy. Conclusions ARM nodes were not infrequently involved in patients with positive SLNs, but they were most often SLNs. Therefore, conservative ALND with ARM is oncologically acceptable in patients with positive SLN.

Identification of Risk Factors Associated with Axillary Lymph Node Metastasis for Sentinel Lymph Node-Positive Breast Cancer Patients

Objective. This study aimed to identify clinicopathological factors related to the extent of axillary lymph node (ALN) involvement in early-stage BC patients with positive sentinel lymph nodes (SLNs). Methods. This was a retrospective analysis of 566 patients in cT1-2N0M0 with 1-2 positive SLNs that underwent axillary lymph node dissection (ALND) at Sun Yat-Sen Memorial Hospital. The clinical and pathologic data from these patients were analyzed. Results. Of these 566 patients, 235 (41.5%) exhibited NSLN metastases. Multivariate analysis revealed that the number of positive SLNs (odds ratio (OR) = 1.511; P = 0.038 ), the ratio of metastatic/dissected SLNs (SLN metastasis rate) (OR = 2.124; P < 0.001 ), and lymphovascular invasion (LVI) (OR = 1.503; P = 0.022 ) were all independent predictors of NSLN metastasis. Patients with 0, 1, 2, or 3 of these risk factors exhibited NSLN metastases in 29.3%, 35.7%, 50.8%, and 68.3% of cases, respectively. We additionally found that the number of positive SLNs (OR = 3.582; P < 0.001 ), SLN metastasis rate (OR = 2.505; P = 0.001 ), LVI (OR = 2.010; P = 0.004 ), and HER2 overexpression (OR = 1.774; P = 0.034 ) were all independent predictors of N2 disease. When individuals had 0, 1, 2, 3, or 4 of these risk factors, they had four or more involved ALNs in 5.2%, 10.8%, 21.1%, 37.5%, and 70.6% of cases, respectively. Conclusion. These results suggest that the number of positive SLNs, the SLN metastasis rate, and LVI are all significant predictors of ALN status in BC patients that have 1-2 positive SLNs and that have undergone ALND. In addition, HER2 overexpression was a significant predictor of N2 disease.

Histopathologic Validation of the Sentinel Node Technique for Early-Stage Cervical Cancer Patients

Background The sentinel lymph node (SLN) biopsy may be an alternative to systematic lymphadenectomy in early cervical cancer. The SLN biopsy is less morbid and has been shown to have high sensitivity for metastasis detection. However, the sensitivity of the SLN technique might be overevaluated because SLNs are examined with ultra-staging, and non-sentinel nodes usually are examined only with routine techniques. This study aimed to validate the negative predictive value (NPV) of the SLN technique by the ultra-staging of SLNs and non-sentinel nodes (NSLNs). Methods The SENTICOL 1 study data published in 2011 were used. All nodes (i.e., SLNs and NSLNs) were secondarily subjected to ultra-staging. The ultra-staging consisted of sectioning every 200 µm, in addition to immunohistochemistry. Moreover, the positive slides and 10% of the negative slides were reviewed. Results The study enrolled 139 patients, and SLNs were detected in 136 (97.8%) of these patiets. Bilateral SLNs were detected in 104 (76.5%) of the 136 patients. A total of 2056 NSLNs were identified (median, 13 NSLNs per patient; range 1–54). Of the 136 patients with SLNs, 23 were shown to have positive SLNs after serial sectioning and immunohistochemical staining. The NSLNs were metastatic in six patients. In the case of bilateral SLN detection, the NPV was 100%, with no false-negatives (FNs). Conclusions The pelvic SLN technique is safe and trustworthy for determining the nodal status of patients with early-stage cervical cancer. In the case of optimal mapping with bilateral detection, the NPV was found to be 100%.

Development of a prediction model based on LASSO regression to evaluate the risk of non-sentinel lymph node metastasis in Chinese breast cancer patients with 1-2 positive sentinel lymph nodes

Background: Our study aimed to investigate the correlative factors influencing non-sentinel lymph node (NSLN) metastasis in Chinese breast cancer patients with 1-2 positive sentinel lymph nodes (SLNs) and to develop an intraoperative prediction model based on the least absolute shrinkage and selection operator (LASSO) algorithm to evaluate the risk of NSLN metastasis.Methods: The factors affecting NSLN status were investigated in a cohort of 714 patients with 1-2 positive SLNs treated at The First Affiliated Hospital of Chongqing Medical University between January 2013 and December 2018. A new mathematical prediction model based on the LASSO algorithm was developed and was validated in a cohort of 131 patients treated between January 2019 and December 2019.Results: In the training cohort, 266/714 (37.3%) patients had NSLN metastasis. In univariate analysis, the histologic grade (P =0.010), number of positive SLNs (P<0.001), number of negative SLNs (P<0.001), number of SLNs dissected (P<0.001), SLN metastasis ratio (P <0.001), lymphovascular invasion (LVI) status (P <0.001), estrogen receptor (ER) status (P =0.011), human epidermal growth factor receptor 2 (HER2) status (P =0.005), molecular subtype (P =0.001), and risk score (P <0.001) were related with NSLN involvement. In multivariate analysis, the histologic grade (P =0.026), LVI status (P =0.005), number of positive SLNs (P=0.001), number of negative SLNs (P=0.005), SLN metastasis ratio (P =0.005), and molecular subtype (P=0.007) were identified as the independent predictors of NSLN metastasis. A LASSO regression-based mathematical prediction model was developed and had an area under the curve (AUC) of 0.764 (95% CI: 0.729-0.798). In the 131-patient validation cohort, the AUC was 0.777 (95% CI: 0.692-0.862).Conclusions: We present a new prediction model to assess the risk of NSLN metastasis in Chinese breast cancer patients with 1-2 positive SLNs. The model was further validated in the validation cohort and showed excellent clinical applicability and diagnostic performance. It can be used as an intraoperative clinical tool for clinicians to predict the risk of NSLN metastasis and make the final decision regarding axillary lymph node dissection (ALND).

Histopathologic validation of the sentinel node technique in early-stage cervical cancer patients.

6028 Background: Sentinel lymph node biopsy (SLN) could be an alternative to systematic lymphadenectomy in early cervical cancer. SLN is less morbid and had shown a high sensitivity for metastasis detection. However, sensitivity of the SLN technique could be over evaluated because SLN are examined with ultrastaging and non sentinel nodes are only examined with routine techniques. The aim of this study was to validate the negative predictive value (NPV) of the SLN technique, with ultrastaging of SLN and non sentinel nodes (NSLN). Methods: We used the SENTICOL 1 study data, published in 2011. All nodes, SLN and NSLN have been secondarily subjected to ultrastaging. The ultrastaging consisted in sectioning every 200 µm and immunohistochemistry. A central reviewing of the positive slides and 10% of the negative slides was undertaken. Results: One hundred thirty-nine patients were included. SLNs were detected in 136 (97.8%) of the 139 patients. SLNs were found bilaterally in 104 (76.5%) of the 136 patients. 2056 NSLNs were identified (median = 13 NSLNs per patient [range 1-54]). Of 136 patients with SLNs detection, 23 had positive SLNs, after serial sectioning and IHC. NSLNs were metastatic in 8 patients. However, in case of bilateral SLN detection, the FN rate was 1/99 (1%) with detection of ITC in one NSLN from 99 bilateral negative SLNs. The NPV was 99% (0,99 [IC 95% = 0,97-1,00]). Conclusions: The pelvic SLN technic is a safe and trustfully technic to determine the nodal status in patients with early-stage cervical cancer. In case of optimal mapping with bilateral detection, NPV is 99% (IC 95% = 0,97-1,00).