Negative Sentinel Lymph Node Biopsy Research Articles

Assessing para-aortic nodal status in high-grade endometrial cancer patients with negative pelvic sentinel lymph node biopsy.

To determine the accuracy of pelvic sentinel lymph node biopsy (SLN) in detecting positive para-aortic (PA) lymph nodes in high-grade uterine cancer, and to determine the recurrence rate in patients with high-grade uterine cancers who did not receive adjuvant chemotherapy based on negative pelvic SLNs. This was a retrospective cohort study of patients with newly diagnosed, high-grade endometrial cancer who underwent surgery, including pelvic SLNs with or without PA node dissection, at a tertiary care institution between 2015 and 2020. Baseline demographics, surgical management, pathology data, and outcomes were analyzed using descriptive statistics, and survival analysis. Postoperative histology of the 110 patients meeting inclusion criteria was 45.5% grade 3 endometrioid, 36.4% serous, 10.9% clear cell, and 7.3% carcinosarcoma. On final pathology, 63.7% were stage 1, and 23.6% were stage 3C with positive nodes. A total of 63 patients (57.3%) had a PA lymph node dissection (56 bilateral, 7 unilateral) in addition to the pelvic SLN. Among this group, 5.8% (95% confidence interval 1.2%-16.0%) had a positive PA node despite a negative pelvic SLN. Among those with a negative pelvic SLN and no adjuvant chemotherapy (n = 75), the rate of distant recurrence was 14.7%, and 3-year recurrence-free survival was 71.9%. The rate of isolated PA node metastasis in high-grade endometrial cancers despite a negative pelvic SLN may be significantly higher than the accepted rate of isolated PA node metastasis in low-grade endometrial cancer. This supports adjuvant treatment decisions continuing to incorporate primary tumor pathology and molecular classification.

8581 Unusual Case of Multifactorial Hyperthyroidism

Abstract Disclosure: D.D. Bagar: None. E. Meyers: None. M. Correia: None. Background: Nivolumab is an immune checkpoint inhibitor that is used to treat specific types of cancer, including melanoma, by increasing the ability of the immune system to detect cancer through activating cytotoxic T-cells. The side effects of immune checkpoint inhibitors are mainly through the overactivation of the immune system that can affect many organs with autoimmune diseases, including endocrine glands, which could be severe and irreversible, like hypothyroidism or immune thyroiditis. The uniqueness of this case is the presence of multifactorial causes of hyperthyroidism; in addition, it is one of the few cases of immune checkpoint inhibitor induced positive TSI thyroiditis.Clinical Case: An 82-year-old male with a known history of atrial fibrillation on amiodarone presented to his dermatologist with a left forearm lesion. A shave biopsy showed melanoma, and he underwent wide local excision with negative sentinel lymph node biopsy. However, he had significant melanoma in situ present within 5 mm of the margin and was deemed not a candidate for further excision. Tumor board recommended close surveillance. He then received two cycles of pembrolizumab for one year, followed by nivolumab. During his treatment course, he had CT scans with iodinated contrast every 8-12 weeks for the clinical trial. At his clinic visit, routine thyroid function tests were significant for hyperthyroidism with a TSH <0.01 and free T4 of 6.07 (0.8-1.8). He was asymptomatic except for unintentional weight loss. He denied using any biotin supplements. His labs also showed positive thyroid stimulating immunoglobulin (TSI) of 1.10 (<=0.54 IU/L). A thyroid US with doppler showed two nodules less than 1.1 cm and no increased vascularity. Amiodarone was discontinued, and prednisone and methimazole were started. His free T4 has since normalized and both prednisone and methimazole are being tapered down. Conclusion: This case is a multifactorial cause of hyperthyroidism. He had been using amiodarone for atrial fibrillation, had multiple imaging studies with iodinated contrast, and was on immune checkpoint inhibitor therapy with a positive TSI. The uniqueness of this case is not only that combined factors can affect thyroid function but also that he developed a positive TSI, which indicates either Graves’ disease or immune-induced thyroiditis by nivolumab, which has been reported only in a few cases. Presentation: 6/3/2024

8581 Unusual Case Of Multifactorial Hyperthyroidism

Abstract Disclosure: D.D. Bagar: None. E. Meyers: None. M. Correia: None. Background: Nivolumab is an immune checkpoint inhibitor that is used to treat specific types of cancer, including melanoma, by increasing the ability of the immune system to detect cancer through activating cytotoxic T-cells. The side effects of immune checkpoint inhibitors are mainly through the overactivation of the immune system that can affect many organs with autoimmune diseases, including endocrine glands, which could be severe and irreversible, like hypothyroidism or immune thyroiditis. The uniqueness of this case is the presence of multifactorial causes of hyperthyroidism; in addition, it is one of the few cases of immune checkpoint inhibitor induced positive TSI thyroiditis.Clinical Case: An 82-year-old male with a known history of atrial fibrillation on amiodarone presented to his dermatologist with a left forearm lesion. A shave biopsy showed melanoma, and he underwent wide local excision with negative sentinel lymph node biopsy. However, he had significant melanoma in situ present within 5 mm of the margin and was deemed not a candidate for further excision. Tumor board recommended close surveillance. He then received two cycles of pembrolizumab for one year, followed by nivolumab. During his treatment course, he had CT scans with iodinated contrast every 8-12 weeks for the clinical trial. At his clinic visit, routine thyroid function tests were significant for hyperthyroidism with a TSH <0.01 and free T4 of 6.07 (0.8-1.8). He was asymptomatic except for unintentional weight loss. He denied using any biotin supplements. His labs also showed positive thyroid stimulating immunoglobulin (TSI) of 1.10 (<=0.54 IU/L). A thyroid US with doppler showed two nodules less than 1.1 cm and no increased vascularity. Amiodarone was discontinued, and prednisone and methimazole were started. His free T4 has since normalized and both prednisone and methimazole are being tapered down. Conclusion: This case is a multifactorial cause of hyperthyroidism. He had been using amiodarone for atrial fibrillation, had multiple imaging studies with iodinated contrast, and was on immune checkpoint inhibitor therapy with a positive TSI. The uniqueness of this case is not only that combined factors can affect thyroid function but also that he developed a positive TSI, which indicates either Graves’ disease or immune-induced thyroiditis by nivolumab, which has been reported only in a few cases. Presentation: 6/3/2024

Sentinel lymph node biopsy for early stage vulvar squamous cell carcinoma

Background Patients with regional lymph node involvement from squamous cell carcinoma (SCC) of the vulva have a 48% 5-year relative survival. Recently, sentinel lymph node (SLN) biopsy has become a viable alternative to inguinofemoral lymphadenectomy. We sought to identify risk factors for predicting a positive SLN in patients with vulvar SCC. Methods A retrospective review of 29 patients with vulvar SCC was performed from 2016 to 2021 at a tertiary care center. Clinicopathologic data were collected in addition to SLN status, including number of lymph nodes removed. Results The average depth of invasion was 7.9 mm, average tumor size was 1.8 cm, 3 of 23 patients had perineural invasion, and 4 of 23 patients had lymphovascular invasion. One patient who did not map on lymphoscintigraphy and five patients with recurrent vulvar SCC were excluded from final analysis. The average number of SLNs removed was two. One patient had a positive SLN: the depth of invasion was 17 mm, tumor size was 5.1 cm, and lymphovascular invasion was present. Conclusions Most patients with early stage vulvar SCC had a negative SLN biopsy. Further study is needed to determine the patient subset that could avoid SLN biopsy altogether.

Triple-Negative Breast Cancer in Older Patients: Does SLNB Guide Therapy?

Older breast cancer patients represent a heterogeneous population. Studies demonstrate that sentinel lymph node biopsy (SLNB) omission may be appropriate in some clinical scenarios, yet patients with triple-negative breast cancer (TNBC) are often excluded from these studies. This study evaluated differences in treatment and survival for older patients with TNBC based on SLNB receipt and result. Patients 70 years old or older with a diagnosis of cT1-2/cN0/M0 TNBC (2010-2019) who underwent surgery were selected from the National Cancer Database. Logistic regression estimated the association of SLNB with therapy, and Cox proportional hazards models estimated the association of SLNB with overall survival (OS) after adjustment for select factors. Of the 15,167 patients included in the study (median age, 77 years), 13.02% did not undergo SLNB, 5.14% had pN1 disease, 0.12% had pN2 disease, and 0.01% had pN3 disease. Most of the patients (83.9%) underwent surgery first, and 16.1% received neoadjuvant chemotherapy. Of those who underwent surgery first and SLNB, 6.2% had pN+ disease. Receipt of SLNB was associated with a higher likelihood of chemotherapy (odds ratio [OR] 1.85; 95% confidence interval [CI] 1.55-2.21), regardless of pN status. Compared with those who did not undergo a SLNB, a negative SLNB was significantly associated with lower mortality (hazard ratio [HR] 0.68; 95% CI 0.63-0.75), although there was no difference for a positive SLNB (HR 1.14; 95% CI 0.98-1.34). The patients receiving chemotherapy first showed no difference in survival based on SLNB receipt or result (p = 0.23). Most older patients with TNBC do not have nodal involvement and do not receive chemotherapy. The receipt and results of SLNB may be associated with outcomes for some who undergo surgery first, but not for those who receive neoadjuvant chemotherapy.

Axillary Recurrence in Sentinel Lymph Node Negative Mastectomy Patients at 16 Years Median Follow Up: Natural History in the Absence of Radiation

BackgroundAxillary recurrence following lumpectomy with a negative sentinel lymph node biopsy (SLNB) is rare, possibly due to routine use of whole breast radiation. In this study, we characterized the rate of any axillary recurrence among mastectomy patients with a negative SLNB and no adjuvant radiation therapy. MethodsWe identified women who underwent mastectomy with SLNB for early-stage breast cancer (1999-2005) and included patients with pathologically negative nodes and no axillary dissection or adjuvant radiation. The primary outcome was ipsilateral axillary recurrence. ResultsA total of 234 women, median age 50 years, underwent 242 mastectomies. Histology showed 112 (46%) invasive cancers, 16 (7%) ductal carcinoma in-situ (DCIS) with microinvasion, and 114 (47%) pure DCIS. Cancers were predominantly estrogen receptor positive (59%) and moderate (41%) or high grade (32%). A mean of 2 final sentinel nodes were excised (range 1-6) and 21 patients (9%) had isolated tumor cells on SLNB pathology. At 16 years median follow up (range 1-22 years), 3 patients (1.2%) developed an isolated axillary failure, and 1 had concurrent axillary and chest wall recurrences (total axillary recurrence rate 1.7%). Three of four axillary recurrences occurred in patients with moderate or high-grade estrogen receptor-positive DCIS without invasion on mastectomy histology. Median time to axillary recurrence was 70.5 months (range 29-132 months). ConclusionsAxillary recurrence is rare after a negative SLNB, even in the absence of adjuvant radiation. This supports the safety of forgoing additional surgery or radiation to the axilla in the early-stage breast cancer and a negative SLNB.

Sentinel lymph node biopsy in early-stage oral squamous cell carcinoma: A retrospective single-center analysis

Sentinel lymph node biopsy (SLNB) is increasingly incorporated in European national guidelines for the management of the clinically node-negative neck (cN0) in early-stage oral squamous cell carcinoma (OSCC). In Germany, SLNB in OSCCs is not yet routinely performed. This study aimed to evaluate the clinical outcome of SLNB in a German cohort.Patients with primary early-stage OSCC who underwent tumor resection and SLNB were retrospectively analyzed. Clinical-pathological characteristics were documented. Primary endpoints were sensitivity and the negative predictive value (NPV).A total of 46 patients with a mean age of 62.3 (±14.5) years met the inclusion criteria. Most tumors were located in the tongue (63.0%). Bilateral drainage from a lateral tumor was observed in three cases (6.5%), and sentinel lymph node metastasis was detected in three patients (6.5%). Mean follow-up for all patients was 13.8 months (±9.6). One patient developed regional recurrence following a negative SLNB during the observation period, leading to an NPV of 0.98 and a sensitivity of 75.0%. The 2-year neck-specific relapse-free survival was 92.8%.SLNB in early-stage OSCC is a reliable diagnostic tool of the cN0 neck, ensuring a high NPV and RFS. SLNB can be advantageous in comparison to elective neck dissection due to the detection of contralateral lymph drainage.

The surgical management of axillary lymph node disease in breast cancer patients

The precise assessment and management of the axillary lymph nodes in breast cancer is crucial for regional control, disease staging, selection of adjuvant chemotherapy strategies, and prediction of prognosis, with a general downward trend in surgical management. For early breast cancer with negative axillary lymph node metastases, sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) as the criterion for axillary status measurement. Patients can be exempted from ALND if they have negative SLNB results. However, it remains to be carefully decided in China whether patients with one or two positive nodes in SLNB can be spared from ALND. However, consensus has been met that patients who meet the criteria of the Z0011 study can be exempted from ALND. For breast cancer patients with positive axillary lymph nodes metastases at the beginning of treatment, the clearance of lymph node disease can be achieved by neoadjuvant therapy, with a reduced rate of complications related to ALND. In particular, there are still many debates associated with SLNB after neoadjuvant therapy, such as whether patients who remain axillary lymph node positive can be spared from ALND. Exploratory and validation studies related to the SLNB avoidance criteria are still controversial. In the future, clinicians should consider the characteristics of patients, the risk of recurrence, and adjuvant treatment regimens to develop individualized axillary lymph node management.

Axillary management and long-term oncologic outcomes in breast cancer patients with clinical N1 disease treated with neoadjuvant chemotherapy

BackgroundLow false negative rates can be achieved with sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients with clinical N1 (cN1) disease. We examined changes in axillary management and oncologic outcomes in BC patients with cN1 disease receiving NAC.MethodsBC patients with biopsy proven cN1 disease treated with NAC were selected from our institutional cancer registry (2014–2017). Patients were grouped by axillary management, axillary lymph node dissection (ALND), SLNB followed by ALND, or SLNB alone. Univariable and multivariable survival analysis for recurrence-free survival (RFS) and overall survival (OS) were performed.Results81 patients met inclusion criteria: 31 (38%) underwent ALND, 25 (31%) SLNB + ALND, and 25 (31%) SLNB alone. A SLN was identified in 45/50 (90%) patients who had SLNB. ALND was performed in 25/50 (50%) patients who had SLNB: 18 for a + SLNB, 5 failed SLNB, and 2 insufficient SLNs. 25 patients had SLNB alone, 17 were SLN- and 8 SLN+. In the SLNB alone group, 23/25 (92%) patients received adjuvant radiation (RT). 20 (25%) patients developed BC recurrence: 14 distant (70%), 3 local (15%), 2 regional + distant (10%), and 1 contralateral (5%). In the SLNB alone group, there was 1 axillary recurrence in a patient with a negative SLNB who did not receive RT. Univariable survival analysis showed significant differences in RFS and OS between axillary management groups, ALND/SLNB + ALND vs. SLNB alone (RFS: p = 0.006, OS: p = 0.021). On multivariable survival analysis, worse RFS and OS were observed in patients with TNBC (RFS: HR 3.77, 95% CI 1.70–11.90, p = 0.023; OS: HR 8.10, 95% CI 1.84–35.60, p = 0.006).ConclusionsSLNB alone and RT after NAC in BC patients with cN1 disease who have negative SLNs at surgery provides long-term regional disease control. This analysis provides support for the practice of axillary downstaging with NAC and SLNB alone.

Sentinel Lymph Node Biopsy in Cutaneous Melanoma: Results of a Single-Center Analysis

Sentinel lymph node biopsy (SLNB) in cutaneous melanoma is a staging step in cases of unaffected regional lymph nodes. This method is included in routine practice in many medical facilities of the Russian Federation.Aim. To analyze the results of SLNB in cutaneous melanoma performed using gamma scintigraphy technique with the 99mTc-containing technefit radiopharmaceutical agent.Materials and methods. The prospective study included 97 patients (39.2 % (38/97) men and 60.8 % (59/97) women) with primary cutaneous melanoma who received surgical treatment at the Republican Clinical Oncological Dispensary (Ufa) between February of 2021 and January of 2023. Mean patient age was 57.2 ± 13.2 years (95 % confidence interval (CI) 53.8–61.3 years), mean Breslow thickness per biopsy and histological examination after wide tumor resection was 2.89 ± 2.7 mm (95 % CI 2.2–3.76 mm), median follow-up period was 14 months (interquartile range 8–18 months). 99mTc-containing technefit radiopharmaceutical agent was administered intradermally around melanoma/scar. Accumulation of the radiopharmaceutical in the regional lymph nodes was evaluated using single-photon emission computed tomography/computed tomography (SPECT/CT). Intraoperatively the sentinel lymph node (SLN) was identified using a portable gamma probe. Morphological evaluation was performed in accordance with the protocol approved at the Republican Clinical Oncological Dispensary and based on the updated protocol of the European Organisation for Research and Treatment of Cancer (EORTС) (2019).Results. The percentage of successfully mapped SLNs after radiopharmaceutical administration was 93.8 % (91/97). Mean number of visualized SLNs per SPECT/CT data was 1.7 ± 1.1 SLN (95 % CI 1.5–1.9). SLN biopsy was performed in 91.8 % (89/97) patients. Mean number of identified SLNs during SLNB was 1.9 ± 1.2 (95 % CI 1.6–2.3). Histological and immunohistochemical examinations showed SLN metastases in 22.5 % (20/89) patients; in 77.5 % (69/89) patients, no lymph node metastases were found. SLN biopsy allowed to perform disease staging. During follow-up in 3 patients with negative SLNs metastases in the regional lymph nodes were found, as well as in 2 patients with positive SLNs. The frequency of false negative SLNB results was 13 % (3/23), negative post-test probability was 2.8 % (2/69). V600E mutation in the BRAF gene was found in 42.3 % (22/52) patients.Conclusion. SLN biopsy using the technefit radiopharmaceutical showed satisfactory results: SLNs were identified in 93.8 % of cases. Morphological examination showed SLN metastases in 22.5 % (20/89) of patients.

Long-term outcomes and patterns of recurrence in patients with thin melanoma and a negative sentinel lymph node biopsy: a single-center experience.

The majority of patients diagnosed with melanoma have thin melanomas (≤1 mm). Data on the rate and pattern of recurrence after a negative sentinel lymph node biopsy (SLNB) are sparse. We retrospectively searched our institutional database and retrieved the records of patients with thin melanomas who underwent an SLNB with negative results. We analyzed patterns of recurrence, time to recurrence, and mode of diagnosis. Thirteen of the 198 patients with thin melanomas and negative SLNB results had tumor recurrence (6.5%): two local in transit (15.4%), three regional (21.3%), and eight distant (61.5%). Distant recurrences tended to occur later than local or regional ones [median disease-free survival = 50 months (95% confidence interval: 36.1-63.9) vs. 34 and 15 months (95% confidence interval: 5.4-24.6), P = 0.005, respectively]. The percentage of patients with tumor thickness ≥0.8 mm was higher among those who sustained recurrence (84.6 vs. 64.9% for no recurrence, P = 0.04). The majority of patients with recurrence were not being followed up when diagnosed (69%), and they are presented because of clinical symptoms. Patients with recurrence had lower survival compared with those without recurrence (median: 118 months vs. ongoing survival, P < 0.001, respectively). Melanoma recurrence in patients with thin melanomas and negative SLNBs is rare, tends to be distant, and negatively affects prognosis. Recurrence tends to occur in patients with melanoma thickness ≥0.8 mm. Further studies are needed to identify patients with high recurrence risk and determine optimal follow-up protocols.

Sex as a predictor of progression-free survival in sentinel node-negative stage II melanoma.

e21560 Background: Adjuvant immunotherapy can improve outcomes for resected stage IIB/C melanoma patients, but also poses challenges. Many patients are cured by surgery alone, making them susceptible to unnecessary treatment risks. Additionally, current staging may overlook some high-risk stage IIA patients who could benefit from immunotherapy. Accurate risk assessment is therefore critical to balance benefits and risks of early immunotherapy and optimise patient selection. This study sought to identify clinicopathologic predictors to refine risk stratification for sentinel lymph node-negative (SLN(-)) stage II melanoma patients, with a focus on the role of sex in prognostic accuracy and treatment personalisation. Methods: We retrospectively analysed 565 stage II melanoma patients with negative sentinel lymph node biopsies at four UK hospitals between 2004-2017. The primary outcome was progression-free survival (PFS). Analysed clinicopathologic factors included Breslow thickness, ulceration sex and tumour-infiltrating lymphocytes (TILs). Univariate and multivariate analyses were conducted. Results: Median follow-up was 9.5 years. Melanoma progression occurred in 24% of patients. Sex emerged as a significant PFS predictor. Specifically, stage IIA and IIB males had higher progression risks than females at the same stages. We also observed disparities across stages; for instance, PFS was significantly worse in stage IIA males than stage IIB females (PFS difference: χ2 = 5.629, p = 0.018), revealing gaps in the prognostic accuracy of current staging systems. Stage IIB females—identified as at risk by current standards—had 5-year PFS of 91%. This highlights potential overestimation of their treatment needs and subsequent risk of undue exposure to treatment toxicity. The sex-based discrepancies observed may be partially explained by differences in antitumor immune function, evidenced by the discovery that Non-brisk TILs-an independent predictor of high progression risk in SLN(-) stage II melanoma- were associated with a 20% reduction in PFS in males vs females (p &lt; 0.001). Conclusions: Significant sex-based PFS disparities exist among sentinel lymph node-negative stage II melanoma patients, with implications for treatment decisions. Incorporating sex enables more refined risk assessment than current substaging alone. Specifically, stage IIA males may be under-recognised for progression risks, while many stage IIB females could face overtreatment. Our findings advocate for nuanced, sex-specific approaches to enhance prognostic accuracy and optimise patient care.

Identifying the high risk group in stage pT1bN0 cutaneous melanoma.

9583 Background: In recent years, there has been a substantial improvement in prognosis for patients diagnosed with stage II or III melanoma due to the advent of adjuvant and neoadjuvant therapy. At the same time, significant percentage of melanoma deaths are caused by prevalent cases of thin melanoma. In this work, we aimed to identify the stage pT1bN0 melanoma subgroup with the worst prognosis. Methods: All cases of stage pT1b melanoma (with negative sentinel node biopsy) treated between 1998 and 2022 in high-throughput reference center were analyzed. Patients were followed for ten years or up to lost to follow-up or death. Patients alive at 10 year mark were censored. The patients were divided into groups with BOTH pT1b features (i.e., Breslow thickness &gt; 0.8mm AND ulceration) vs those with just ONE of those features. Additionally, patients’ sex, the tumor’s pathological subtype, and mitotic index were analyzed. The Kaplan-Meier and the Cox proportional model were used in statistical analysis. Results: There were 665 cases identified. 63% of patients were female, median age was 49 (IQR: 38-60). 70% of patients were classified as pT1b due to Breslow thickness, 21% due to ulceration and 9% due to BOTH features. 48% of patients had superficially spreading melanoma, 3% - acral, 9% - nodular while other patients had other/unspecified subtype. The median mitotic index was 1/mm2, but this feature was missing in 46% of cases. Overall, 61 patients died during the follow-up. The 10-year overall survival (OS) rate for the whole group was 86% (95% CI: 83-90%). In a multivariable model, patients with BOTH IB features (HR 2.1, 95%CI:1.1-4.2), nodular or acral melanoma (HR 2.2, 95%CI:1.2-4.1) and males (HR 2.6, 95%CI:1.6-4.4) had worse prognosis; the mitotic index was not predictive for OS in this model. In patients with BOTH pT1b features the 10 year survival rate was 75% (95%CI: 62-89) and 87% (95%CI: 84-91%) in case of just one feature (log-rank p=0.008). Conclusions: There is a specific subgroup of patients diagnosed with stage IB who have a relatively bad prognosis. Focusing on perioperative treatment or on a more strict follow-up schedule in this group may prove beneficial.

A phase III randomized trial of radiotherapy optimization for low-risk HER2-positive breast cancer (HERO): NRG-BR008.

TPS613 Background: Breast radiotherapy (RT) is the standard of care for patients with early-stage breast cancer (BC) who undergo breast-conserving surgery (BCS). However, the magnitude of benefit of RT is less clear in BCS patients with low-risk disease who receive effective systemic therapy. Among patients with early-stage HER2-positive (HER2+) BC, 10-year locoregional recurrence has been reported as low as 1.5% following BCS, adjuvant chemotherapy and HER2-targeted therapy, and RT. Given these exceedingly favorable outcomes, with the addition of HER2-directed therapy, we seek to evaluate the feasibility of omitting RT among patients with early-stage HER2+ BC following BCS and appropriate systemic therapy. Methods: This is a phase III randomized trial for patients ≥40 years with early-stage, node-negative, HER2+ (IHC/FISH) BC treated with BCS with negative margins and sentinel lymph node biopsy or axillary dissection. Patients undergoing primary surgery must have pathologic T1 (≤2 cm) N0 disease, while patients receiving neoadjuvant therapy must have clinical T1-2 (with radiographically T≤3.0 cm) N0 disease and exhibit a pathologic complete response (ypT0N0) at surgery. All patients must receive cytotoxic chemotherapy and HER2-targeted therapy, either in the adjuvant or neoadjuvant setting. Stratification is by age (&lt;60; ≥60), tumor size (≤1 cm; &gt;1 cm), estrogen-receptor status (positive; negative), and systemic therapy sequencing (adjuvant vneoadjuvant). Patients will be randomized to standard breast RT in addition to continuation of trastuzumab to complete one year of treatment (Arm 1), or trastuzumab alone (Arm 2). Endocrine therapy will be recommended for patients with hormone-receptor positive tumors. The primary endpoint is the recurrence-free interval (RFI). Secondary endpoints include time to ipsilateral breast recurrence, locoregional recurrence, disease-free survival, and overall survival, in addition to the 7-year ipsilateral breast recurrence rate among those not receiving RT. A health-related quality of life sub-study will assess differences in patient-reported breast pain and worry. We estimate a 7-year RFI of 97.5% with RT and allow for a clinically acceptable decrement of 3.63% without RT (7-year RFI of 93.87%; HR 2.5) to establish omission of RT as non-inferior. NRG-BR008 aims to enroll 1,300 patients over 4.5 years, yielding 80% power to detect the non-inferiority of RT omission with a one-sided α=0.05. We expect to observe the required 38 RFI events within 6 years of additional follow-up. The NRG-BR008/HERO trial opened to accrual in March 2023. Accrual is 13/1,300 as of 02-05-2024. Clinical trial information: NCT05705401 .

Abstract PO1-19-01: NRG-BR008: A Phase III Randomized Trial of Radiotherapy Optimization for Low-risk HER2-positive Breast Cancer (HERO)

Abstract Background: Breast radiotherapy (RT) is the standard of care for patients with early-stage breast cancer (BC) who undergo breast-conserving surgery (BCS). However, the magnitude of benefit of RT is less clear in BCS patients with low-risk disease who receive effective systemic therapy. Among patients with early-stage HER2-positive (HER2+) BC, 10-year locoregional recurrence has been reported as low as 1.5% following BCS, adjuvant chemotherapy and HER2-targeted therapy, and RT. Given these exceedingly favorable outcomes, with the addition of HER2-directed therapy, we seek to evaluate the feasibility of omitting RT among patients with early-stage HER2+ BC following BCS and appropriate systemic therapy. Methods: This is a phase III randomized trial for patients ≥40 years with early-stage, node-negative HER2+ (IHC/FISH) BC treated with BCS with negative margins and sentinel lymph node biopsy or axillary dissection. Patients undergoing primary surgery must have pathologic T1 (&amp;lt; 2 cm) N0 disease, while patients receiving neoadjuvant therapy must have clinical T1-2 (with radiographically T&amp;lt; 3.0 cm) N0 disease and exhibit a pathologic complete response (ypT0N0) at surgery. All patients must receive cytotoxic chemotherapy and HER2-targeted therapy, either in the adjuvant or neoadjuvant setting. Stratification is by age (&amp;lt; 60; ≥60), tumor size (≤1 cm; &amp;gt;1 cm), estrogen-receptor status (positive; negative), and systemic therapy sequencing (adjuvant vs neoadjuvant). Patients will be randomized to standard breast RT in addition to continuation of trastuzumab to complete a year of treatment (Arm 1), or trastuzumab alone (Arm 2). Endocrine therapy will be recommended for patients with hormone-receptor positive tumors. The primary endpoint is the recurrence-free interval (RFI). Secondary endpoints include the time to ipsilateral breast recurrence, locoregional recurrence, disease-free survival, and overall survival, in addition to the 7-year ipsilateral breast recurrence rate among those not receiving RT. A health-related quality of life sub-study will assess differences in patient-reported breast pain and worry. We estimate a 7-year RFI of 97.5% with RT and allow for a clinically acceptable decrement of 3.63% without RT (7-year RFI of 93.87%; HR 2.5) to establish omission of RT as non-inferior. NRG-BR008 aims to enroll 1,300 patients over 4.5 years, yielding 80% power to detect the non-inferiority of RT omission with a one-sided α=0.05. We expect to observe the required 38 RFI events within 6 years of additional follow-up. The NRG-BR008/HERO trial opened to accrual in March, 2023. NCT05705401. Support: U10CA180868, -180822, UG1CA189867, U24CA196067; Susan G. Komen Foundation (JR) Citation Format: Lior Braunstein, Melissa Mitchell, Hanna Bandos, William Sikov, Atif Khan, Peter Chen, Patricia Ganz, Reshma Jagsi, Julia White, Reena Cecchini, Hyejoo Kang, Shannon Puhalla, Kelly Bolton, Eileen Connolly, Erica Stringer-Reasor, Kimberly Gergelis, Thomas Julian, Eleftherios Mamounas, Norman Wolmark. NRG-BR008: A Phase III Randomized Trial of Radiotherapy Optimization for Low-risk HER2-positive Breast Cancer (HERO) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-19-01.

Efficacy of sentinel lymph-node biopsy after neoadjuvant chemotherapy in clinically axilla node-negative patients.

Breast cancer is the most common cancer in women. Developments in breast cancer treatment have extended the life expectancy of these patients, raising the issue of morbidity of breast cancer surgery, the major cause of which is axillary dissection. The aim of the present study was to establish the safety of sentinel node biopsy (SLNB) in patients with a clinically node-negative axilla after neoadjuvant chemotherapy (NACT). We recorded demographic data, as well as the findings of physical examination, imaging, and pathology before and after NACT. SLNB with indocyanine green + isosulfan blue and axillary dissection were performed and the surgical and pathology findings were recorded. A sentinel lymph node was detected in 80 of 90 patients who underwent surgery. When ≥ three sentinel lymph nodes were removed as negative in the patient group with cN0 after treatment, we evaluated the axilla as being negative with an accuracy of 100%. Axillary lymph-node dissection may not be necessary for patients with cNO confirmed by physical and radiological examination using positron emission tomography (PET) computed tomography (CT), and breast magnetic resonance imaging (MRI) after NACT, if ≥ three negative SLNB are removed. Further studies are needed to confirm our findings.

Sentinel Node Navigation Surgery for Early Gastric Cancer: A Narrative Review.

Early gastric cancer (EGC) refers to malignant tumor lesions that are limited to the mucosa and submucosa layers, regardless of the presence of lymph node metastasis. Typically, EGC has a low rate of perigastric lymph node metastasis, and long-term survival outcomes are good after radical surgical treatment. The primary objective of surgical treatment for EGC is to achieve functional preservation while ensuring a radical cure. Sentinel node navigation surgery (SNNS) is a surgical technique used in the treatment of EGC. This approach achieves functional preservation by limiting lymph node dissection and performing restrictive gastrectomy guided by intraoperative negative sentinel node (SN) biopsy. Despite the apparent improvement in the detection rate of SN with the emergence of various tracing dyes and laparoscopic fluorescence systems, the oncological safety of SNNS remains a controversial research topic. SNNS, as a true form of stomach preservation surgery that enhances the quality of life, has become a topic of interest in the EGC field. In recent years, scholars from Japan and South Korea have conducted extensive research on the feasibility and safety of SNNS in the treatment of EGC. This article aims to provide reference choices for surgeons treating EGC by reviewing relevant research on SNNS for EGC in recent years.

Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in cN0 Breast Cancer: Impact of HER2-Positive Status on Survival.

High rates of negative sentinel lymph node biopsy (SLNB) in clinically node-negative (cN0) breast cancer (BC) after neoadjuvant chemotherapy (NAC) have been described. These results are associated with triple-negative (TNBC) and human epidermal growth factor receptor 2 (HER2+) subtypes achieving pathologic complete response (pCR). This study evaluates predictive variables and survival in order to assess the possible omission of SLNB after NAC. Prospective study of women with cN0 BC treated with NAC and subsequent surgery, between April 2010 and May 2021. SLNB technique included, performing axillary lymphadenectomy in the absence of detection or SLNB-positivity. Multivariable logistic regression was used for analysis of NAC-response and SLNB-results in molecular subtypes: HR-/HER2+, TNBC, HR+/HER2- and HR+/HER2+. Kaplan-Meyer and log-rank were used for survival analysis. A total of 179 patients (50.5±10.1 years) were included. Of these, 39.7% achieved pCR (ypT0/Tis). HR-negative subtypes had higher pCR rates (HR-/HER2+: 59.4%; TNBC: 53.4%), with no cases of SLNB-positive. With residual disease, HR-/HER2+ and TNBC showed low rates of SLNB-positivity (6.7% and 10.3%) versus HR+ (HR+/HER2+: 20%; HR+/HER2-: 44%; p<0.001). Multivariable analysis identified independent predictors of SLNB-negativity (p<0.0001) to be: HR- [odds ratio (OR)=0.15; 95% confidence interval (CI): 0.06-0.37; p = 0.0001], HER2+ (OR=0.34; 95% CI: 0.14-0.81; p = 0.015) and high-grade Nottingham (OR=0.42; 95% CI: 0.18-0.99; p = 0.048). Disease-free survival showed worse outcomes with SLNB-positivity (p<0.0001), HR+/HER2- (p = 0.0277), larger tumor size (p = 0.002) and residual disease after NAC (p<0.0001). Patient selection based on NAC response, molecular subtype, and survival outcomes is a priority for establishing individualized therapeutic strategies after NAC. Molecular subtypes with higher pCR rates and lower rates of SLNB-positivity could benefit from non-invasive strategies that include omission of SLNB.

The Role of Sentinel Node Biopsy in the Era of Adjuvant Therapy for Melanoma.

Sentinel lymph node biopsy (SLNB) is a surgical procedure aimed to detect nodal metastases in patients with clinically occult disease. Since the advent of new systemic therapies, its role in melanoma has been extensively debated over the last years. In this article, three possible scenarios are discussed, considering the SLNB impact on the management of melanoma patients. First, pT1b and pT2a patients with negative SLNB (stages IA and IB) and those with positive SLNB (stage IIIA) would all not benefit from adjuvant treatment. Therefore, SLNB might be avoided in these categories of patients. Second, in IIB and IIC, melanoma patients are already candidates for adjuvant treatment; therefore, SLNB in patients with T3b, T4a, or T4b melanoma would not change treatment decisions. On the other end of the spectrum, patients with pT2b and pT3a melanomas (clinical stage IIA) represent the only two groups whose management would be significantly affected by the SLNB status, being adjuvant therapy only indicated for SLN-positive patients. Further studies are needed to investigate which melanoma patient deserves SLNB.

Pathological characteristics predicting sentinel lymph node metastasis in early breast cancer patients.

In this study, we aimed to identify the predicting pathological factors affecting sentinel lymph node biopsy (SLNB) in patients with clinically node-negative breast cancer. Our single institution retrospective study was conducted at the Cancer Research Center of Shahid Beheshti University of Medical Sciences from 2018 to 2021. Data were imported into and analyzed using SPSS Version 28 for Windows (IBM Corp., Armonk, NY, USA). Of the 76 patients who underwent SLNB, 43 (56.6%) had negative SLNB and 33 (43.4%) had positive SLNB which led to axillary lymph node dissection (ALND). The relationship between hormone receptor status (ER/PR/Her2), pathology type (IDC, ILC, DCIS, LCIS), tumor size, and Ki67 expression was assessed. According to the results, axillary lymph node involvement can be predicted based on the scores and results of the three variables: IDC tumor type, lympho vascular invasion (LVI), and Ki67 expression. The positive relationship between IDC tumor type and LVI with SLNB indicates that with positive IDC tumor type and LVI, there is a higher probability of positive axillary lymph nodes (3.88 times higher probability for IDC tumor type and 6.75 times higher probability for the LVI factor). However, when the Ki67 expression is lower, the probability of positive axillary lymph nodes is higher (3.58 times higher probability). IDC tumor type, LVI, and lower Ki67 expression are independent predictive factors of positive SLNB.