Negative Sentinel Lymph Node Biopsy Research Articles

Abstract PD4-05: Axillary recurrence is a rare event in node-positive patients. treated with sentinel node biopsy alone after neoadjuvant chemotherapy: Results of a prospective study

Abstract Background: Four prospective multi-institutional trials have demonstrated that clinically node-positive patients (cN1) who receive neoadjuvant therapy (NAC) and convert to cN0 can be reliably staged with sentinel lymph node biopsy (SLNB) with false-negative rates (FNRs) of < 10%, when ≥ 3 SLNs are retrieved. Since study patients all had axillary lymph node dissection (ALND), the rate of axillary recurrence after SLNB alone is unknown. Of concern is the possibility that residual chemotherapy-resistant axillary disease could lead to higher recurrence rates than seen in the primary surgery setting for cN0 patients where SLN FNRs of 5-10% result in axillary recurrence in < 1% of cases. Here we report regional recurrence rates in a prospectively defined cohort of cN1 patients receiving NAC, followed by a negative SLNB using a standardized technique, and no further axillary surgery. Methods: From 06/2014 to 02/2019, patients with cT1-3 biopsy-proven cN1 breast cancer who received NAC and converted to cN0 by physical exam were prospectively managed with SLNB with dual tracer mapping and omission of ALND if ≥ 3 SLNs were pathologically negative. Nodes were not routinely clipped, and retrieval of clipped metastatic nodes was not required. Pathologically negative SLNs were defined as the absence of any metastases including isolated tumor cells. Results: Of 610 cN1 patients treated with NAC, 555 (91%) converted to cN0 and had SLNB; 234 (42%) had ≥ 3 negative SLNs and were treated with SLNB alone. Median patient age was 49 years and median tumor size at presentation was 3 cm; 61% were HER2+ and 18% triple negative. Most (91%) received doxorubicin-based NAC and 88% received adjuvant radiotherapy (RT), with 80% (n = 164) of RT patients receiving nodal RT (Table). At a median follow-up of 35 months, there was only 1 (0.4%) axillary recurrence for the entire cohort, synchronous with a breast recurrence, in a patient who refused RT. Among patients who received RT (n = 205), there were no axillary recurrences. The 4-year rate of distant recurrence for all patients was 6.1% (95% CI, 3.4-10.7%) and 4-year overall survival was 93.9% (95% CI, 87.6-97.1%). Conclusion: In cN1 patients treated with NAC, rates of axillary recurrence in patients with ≥ 3 pathologically negative SLNs treated with SLNB alone were low, without routine nodal clipping. Although further follow-up is needed, multiple studies have shown that nodal recurrence is an early event, particularly in HER2+ and triple negative patients, who comprised the majority of the population. Our findings support omitting ALND in cN1 patients after NAC when the SLNs are negative using an optimal SLNB technique. Table. Patient PopulationOverall cohort (n = 234)Age, years (median, IQR)49 (40, 58)Tumor size at presentation, cm (median, IQR)3.0 (2.2, 5.0)Number SLNs retrieved (median, IQR)4 (3, 5)Palpable nodes at presentation (n, %)179 (76%)HistologyDuctal211 (90%)Lobular and mixed7 (3%)Micropapillary and mixed10 (4%)Other3 (1%)Occult3 (1%)DifferentiationWell1 (0.5%)Moderate36 (15%)Poor196 (84%)Unknown1 (0.5%)Receptor StatusHR+/HER2-47 (20%)HR+/HER2+80 (34%)HR-/HER2+64 (27%)HR-/HER2-43 (18%)Breast SurgeryBCS118 (50%)Mastectomy116 (50%)Breast pCR¥Yes161 (70%)No70 (30%)NAC regimenAC-T197 (84%)AC-T + carbo15 (6.4%)TC8 (3.4%)Other14 (6%)Neoadjuvant anti-HER2 treatmentHP (dual-therapy)144 (100%)Adjuvant RTYes205 (88%)No*29 (12%)¥3 patients had occult primary breast cancer and were not included in breast pCR calculation; *6/29 patients who did not receive RT enrolled in NSABP B-51 Citation Format: Andrea V Barrio, Giacomo Montagna, Anita Mamtani, Varadan Sevilimedu, Hiram S Cody, III, Mahmoud El-Tamer, Mary L Gemignani, Alexandra S Heerdt, Tracy-Ann Moo, Melissa Pilewskie, George Plitas, Lisa Sclafani, Kimberly J Van Zee, Monica Morrow. Axillary recurrence is a rare event in node-positive patients. treated with sentinel node biopsy alone after neoadjuvant chemotherapy: Results of a prospective study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD4-05.

Post-operative follow-up of 150 patients with sentinel lymph node biopsy under tumescence local anesthesia.

Sentinel lymph node biopsy (SLNB) is useful for staging of patients with melanoma. Although SLNB is mostly performed under general anesthesia (GA), tumescence local anesthesia (TLA) can also be used. However, less data are available regarding feasibility of SLNB under TLA. Here we present a post-operative follow-up of 150 patients. We prospectively analyzed data from 150 patients with primary cutaneous malignant melanoma. We assessed pain, post-operative complications and patients' satisfaction after SLNB under TLA. 32% of the patients reported post-operative pain within the first 48h after SLNB. Seroma was the most frequent complication, as 29 seromas after SLNB were observed. Wound infection was observed in 3.3% of the patients. 98.7% of the patients were satisfied with SLNB under TLA. SLNB under TLA is a safe and feasible option and should be considered for patients with melanoma. Especially with multimorbid or elderly patients, the risks of GA can be avoided.

Sentinel Node Biopsy in Ductal Carcinoma in Situ: Is it Justifiable?

Background: For invasive breast cancer, sentinel node biopsy (SNB) is an acceptable alternative to axillary node clearance (ANC), although in the recent era, its role is under review. In ductal carcinoma in situ (DCIS), the benefit of SNB is even less well defined. Despite this, guidelines still recommend that it is performed in selected cases of DCIS. The aim of our study was to evaluate the diagnostic value of performing SNB in DCIS.Methods: Patients with a diagnosis of DCIS who underwent axillary staging with SNB between 2008-2019 in our large volume tertiary centre were identified and included in the study.Results: Out of the 48 patients who were identified, four patients had a positive SNB (8%). Two of those patients were found to have micro metastatic disease. None of the patients with a positive SNB had local or systemic recurrence (median follow up: 40 months). One non-breast cancer-related mortality was reported. Two patients were identified who had recurrent disease, one with an invasive recurrence in the breast, and the other with systemic recurrence in the form of bone disease. Both of these patients had a negative SNB.Conclusion: Our results confirm that performing axillary staging with SNB in DCIS is not justifiable, as it does not affect patient outcomes. This supports the emerging evidence that being more surgically conservative may decrease morbidity without affecting patient survival.

SURGICAL TREATMENT FOR BREAST CANCER AND AXILLARY METASTASES: HISTORICAL PERSPECTIVE

Breast cancer (BC) is the most common malignancy to affect females. The first suggestions of BC and its treatment date back to Ancient Egypt, 1500-1600 B.C. Throughout history, the management of BC has evolved from extensive radical mastectomy towards less invasive treatments. Radical mastectomy was introduced by W.S. Halsted in 1894, involving the resection of the breast, regional lymph nodes, pectoralis major and minor. Despite its mutilating effect, it had been the main surgical approach to BC patients until 1948, when Patey and Dyson proposed its modified form that conserved pectoralis major and minor and the level III of axillary lymph nodes. The latter was associated with less postoperative morbidity and improved quality of life. The idea of limited breast tissue resection was introduced in the 1970s by Umberto Veronesi and led to further minimizations of surgery in BC patients until breast conservation became the standard of care for early-stage disease. In the 1990s, intraoperative lymphatic mapping and the concept of sentinel lymph node (SLN) biopsy (SLNB) have been developed. SLNB has replaced axillary lymph node dissection (ALND) to be the standard procedure for axillary staging in patients with clinically node-negative BC. Many women have since been spared ALND, including those with negative SLNB or with SLNs involved with micrometastases (0.2-2 mm in size). In the last decade, evidence gathered from new clinical trials suggests that ALND may be safely omitted even in BC patients with 1 or 2 positive SLNs if adjuvant radiotherapy is delivered.

Patient Selection for Surgery vs Radiotherapy for Early Stage Oropharyngeal Cancer.

Surgery and radiation therapy are both commonly used in the treatment of early stage (AJCC stages T1-T2 N0-M0) oropharyngeal squamous cell carcinoma (OPSCC). Transoral robotic surgery (TORS) and intensity modulated radiation therapy (IMRT) have been reported to result in similar survival and disease control outcomes. However, their side effect profiles widely differ. Nevertheless, patients who experience the worst side effects and quality of life are the ones who receive the combination of TORS and adjuvant radiation or chemoradiation therapy. Thus, appropriate patient selection for surgery to minimize the need for multimodality therapy is key. We propose, in this paper, the use of sentinel lymph node biopsy in the node negative (N0) neck as a means that is worth exploring for selecting patients to either radiation therapy or surgery. Patients with a positive sentinel lymph node (SLN) would be better directed to upfront radiation. On the contrary, patients with a negative SLN biopsy would be more confidently directed towards TORS and neck dissection alone.

Complications and outcomes following inguinal lymphadenectomy for malignant melanoma in an Asian population.

Melanoma is a potentially fatal cutaneous malignancy and regional lymph node (LN) metastases are the most important predictors of mortality. This study aimed to analyze clinical features and risk factors of complications associated with inguinal LN dissection (LND) to establish treatment protocols. This single-center retrospective study (2000 to 2018) consisted of patients who underwent inguinal area sentinel LN biopsy (SLNB) or LND due to malignant melanoma. Risk factors and outcomes were analyzed. One hundred patients underwent SLNB alone (n=67; patients with negative SLNB), complete LND (CLND) after positive SLNB (n=19), or radical LND without SLNB (n=14). Five-year overall survival and disease-free survival rates among these groups were 87.3%, 57.4%, and 61.9%, and 59.0%, 22.7%, and 28.1%, respectively. The complication rate in the SLNB alone group was lower than the other groups (22.4% vs. 47.4% and 35.7%, respectively; P=0.048). Seroma was the most common complication in the SLNB alone group (15.0%); lymphedema was most common in the CLND after SLNB group (21.1%). Multivariate analysis of risk factors for postoperative complications found the hazard ratio for body mass index >28 kg/m2 was 4.376 (95% confidence interval [CI], 1.243-15.401; P=0.022). The hazard ratio for LND (including CLND after SLNB and radical LND without SLNB) was 3.263 (95% CI, 1.248-8.529; P=0.016). Inguinal LND is a higher risk procedure compared to SLNB and other sites for postoperative complications, irrespective of meticulous surgical techniques. More studies are needed to establish treatment protocols (e.g., observation vs. CLND after a positive SLNB result) and the risks and benefits in Asian populations.

Evaluation of internal mammary lymph node biopsy during microsurgical breast reconstruction: An analysis of 230 consecutive patients.

Clinical significance of internal mammary (IM) lymph node biopsy during microvascular free flap breast reconstruction remains controversial. Some microsurgeons may choose to biopsy an IM lymph node during routine IM vessel dissection. The authors reviewed the results of IM lymph node biopsy during autologous breast reconstruction. A retrospective chart review of patients who underwent autologous breast reconstruction during a seven-year period (January 2010 to January 2017) was performed. Patient demographic data, disease staging, flap details, pathology reports, and adjuvant treatment were evaluated. A total of 230 patients with a mean age of 52.1 (SD 9.3) underwent IM lymph node biopsy (n=297). Single IM lymph node was removed in 169 patients, 2 nodes were removed in 56 patients, 3 nodes in 4 patients, and 4 nodes in a single patient. Histopathologic analysis demonstrated presence of IM lymph node metastasis in 16 patients (7.0%). Thirteen patients were found to have metastatic IM lymph nodes in the setting of immediate reconstruction. Three patients were found to have metastatic IM lymph nodes in the setting of delayed. Five out of 16 patients (31.3%) had negative axillary sentinel lymph node biopsy and IM lymph nodes were the only site of nodal metastases. All five of these patients were upstaged accordingly and received adjuvant therapy based on the discussion at the multidisciplinary breast tumor conference. Opportunistic internal mammary lymph node sampling during autologous breast reconstruction can be performed with minimal morbidity and has significant impact on the disease staging and adjuvant treatment.

Locoregional relapse is a strong prognostic indicator of distant metastatic progression in breast cancer patients after negative sentinel lymph node biopsy.

Sentinel lymph node biopsy is routinely used in breast cancer patients with clinically negative axillary lymph nodes. Locoregional relapses after negative sentinel lymph node biopsy are infrequent, occurring in up to 3% of patients. Six thousand and eight patients underwent breast cancer surgery in our center between 2006 and 2015. We analyzed 1466 patients with negative sentinel lymph node biopsy and no prior systemic treatment. Mastectomy without irradiation was used in 25.4% of these patients and breast-conserving surgery with adjuvant radiotherapy in 74.6%. Forty-seven (3.21%) locoregional relapses were identified within a median of 51months (10-138months). The molecular type was analyzed as a risk factor for locoregional relapses and distant metastases. The locoregional relapse location was then analyzed as a risk factor for distant metastases. Triple-negative breast cancer (P=.003), age <40year (P=.007), multifocality (P=.011), and mastectomy (P<.0001) were risk factors for locoregional relapses. Patients who developed locoregional relapses more frequently developed distant metastases (P<.0001). The distribution of molecular types did not differ significantly in patients with locoregional relapses and distant metastases, concentrating in triple-negative and Luminal B tumor cases with distant metastases in almost 58% of cases, while not occurring in Luminal A patients. The locoregional-to-distant metastasis interval was shorter in cases of chest wall and lymph nodes relapse compared with breast-only relapse locations(P=.028). Molecular type, especially triple-negative, young age, mastectomy without adjuvant irradiation, and multifocality are risk factors for locoregional relapse in sentinel lymph node biopsy negative breast cancer patients. Locoregional relapse is an important risk factor for developing distant metastasis, except in Luminal A breast cancer patients and those who suffer from breast-only relapse.

A negative binomial regression model for risk estimation of 0\u20132 axillary lymph node metastases in breast cancer patients

Extensive clinical trials indicate that patients with negative sentinel lymph node biopsy do not need axillary lymph node dissection (ALND). However, the ACOSOG Z0011 trial indicates that patients with clinically negative axillary lymph nodes (ALNs) and 1–2 positive sentinel lymph nodes having breast conserving surgery with whole breast radiotherapy do not benefit from ALND. The aim of this study is therefore to identify those patients with 0–2 positive nodes who might avoid ALND. A total of 486 patients were eligible for the study with 212 patients in the modeling group and 274 patients in the validation group, respectively. Clinical lymph node status, histologic grade, estrogen receptor status, and human epidermal growth factor receptor 2 status were found to be significantly associated with ALN metastasis. A negative binomial regression (NBR) model was developed to predict the probability of having 0–2 ALN metastases with the area under the curve of 0.881 (95% confidence interval 0.829–0.921, P < 0.001) in the modeling group and 0.758 (95% confidence interval 0.702–0.807, P < 0.001) in the validation group. Decision curve analysis demonstrated that the model was clinically useful. The NBR model demonstrated adequate discriminative ability and clinical utility for predicting 0–2 ALN metastases.

Post-operative surveillance following negative sentinel node biopsy: our 3 year experience

Post-operative surveillance following negative sentinel node biopsy: our 3 year experience

Sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with node-positive breast cancer: guiding a more selective axillary approach.

The role of sentinel lymph node biopsy (SLNB) in breast cancer patients who undergo neoadjuvant chemotherapy (NAC) remains controversial. This study aims to investigate if axillary lymph node dissection (ALND) could be safely omitted after a negative SLNB in cN1/2 patients who become cN0 after NAC. We retrospectively assessed T1-4, cN1/2 patients who were submitted to NAC between 2010 and 2016. T1-T3 patients who achieved complete axillary clinical response underwent SLNB. Those whose SLNs were negative were not subjected to additional ALND. The oncological outcomes of the patients were analyzed. Fifty-nine T1-T3 patients (45.0%) achieved a complete axillary response (cN0), and were selected to undergo SLNB. SLNs were detected in 55 of them (93.2%). Seventeen of those patients (30.9%) had SLN metastases detected and subsequently underwent ALND. In contrast, 38 patients (69.1%) had no nodal metastases detected and were managed without complementary ALND. After a mean follow-up of55.8months, only one patient (2.6%) submitted to SLNB without a complementary ALND had axillary recurrence as compared with three patients (3.2%) in the ALND group (p = 0.71). Distant recurrence occurred more frequently among patients submitted to ALND (92.1%) than among those only submitted to SLNB (7.9%) (p < 0.0006). Overall survival and disease-free survival were significantly better in patients who were not submitted to ALND. SLNB could be successfully used in guiding a more selective axillary approach in cN+ patients that became cN0 after NAC. Omitting ALND in CN0 patients with negative SLNs did not seem to compromise disease control and oncological outcomes.

The prognostic impact of mode of detection of axillary metastases for women with invasive breast cancer: A retrospective observational study

AimTo identify the breast cancer specific survival (BCSS) associated with nodal metastasis identified by axillary core biopsy (ACB), and by sentinel node biopsy (SNB) compared with node negative patients. A further aim was to assess the prognostic effects of axillary ultrasound (US) features and amount of tumour in ACB specimens. MethodsConsecutive patients with cancer were identified from a database of US lesions undergoing breast biopsy. The three study groups were: a) those with metastasis identified by ACB, b) those undergoing immediate surgery with positive SNB and c) those undergoing immediate surgery with a negative SNB. US features and the amount of tumour in the ACB specimen were assessed by review of US images and pathological reports. BCSS was assessed using Kaplan Meier survival curves. Results967 patients were included, with mean follow-up of 6.0 yrs. There were 90 breast cancer deaths: 26% of those with a positive ACB, 11% with a positive SNB and 4% of those with a negative SNB. BCSS was significantly different between the groups (p < 0.001) with hazard ratio, compared with the negative SNB group, of 7.8 (95% CI 4.4–13.7) for patients with positive ACB and 2.5 (95% CI 1.3–4.6) for positive SNB. Axillary US findings and assessment of the amount of tumour in the ACB did not influence survival. ConclusionThis study suggests that women with a positive ACB have a worse BCSS compared to those with a positive SNB. This should be borne in mind when systemic therapy is being considered.

First Intraoperative Radiation Therapy Center in Africa: First 2 Years in Operation, Including COVID-19 Experiences.

PURPOSEThere is a shortage of radiation therapy service centers in low- to middle-income countries. TARGIT–intraoperative radiation therapy (IORT) may offer a viable alternative to improve radiation treatment efficiency and alleviate hospital patient loads. The Breast Care Unit in Johannesburg became the first facility in Africa to offer TARGIT-IORT, and the purpose of this study was to present a retrospective review of patients receiving IORT at this center between November 2017 and May 2020.PATIENTS AND METHODSPatient selection criteria were based mainly on the latest American Society of Radiation Oncology guidelines. Selection criteria included early-stage breast carcinoma (luminal A) and luminal B with negative upfront sentinel lymph node biopsy that negated external-beam radiation therapy (EBRT). Patient characteristics, reasons for choosing IORT, histology, and use of oncoplastic surgery that resulted in complications were recorded.RESULTSOne hundred seven patients successfully received IORT/TARGIT-IORT. Mean age was 60.8 years (standard deviation, 9.3 years). A total of 73.8% of patients presented with luminal A, 15.0% with luminal B, and 5.6% with triple-negative cancer. One patient who presented with locally advanced breast cancer (T4N2) opted for IORT as a boost in addition to planned EBRT. Eighty-seven patients underwent wide local excision (WLE) with mastopexy, and 12 underwent WLE with parenchymal. Primary reasons for selecting IORT/TARGIT-IORT were distance from the hospital (43.9%), choice (40.2%), and age (10.3%).CONCLUSIONThis retrospective study of IORT/TARGIT-IORT performed in Africa confirms its viability, with low complication rates and no detrimental effects with breast conservation, resulting in positive acceptance and the potential to reduce Oncology Center patient loads. Limitations of the study include the fact that only short-term data on local recurrence were available. Health and socioeconomic value models must still be addressed in the African setting.

Expression of IMP3 in a retrospective cohort of melanomas with selective lymph node biopsy.

Insulin-like growth factor-II mRNA-binding protein 3 (IMP-3), which is a member of the insulin-like growth factor mRNA-binding protein family, is expressed at high levels in many types of cancer, where it plays an important role in cell proliferation, as well as in the processes of invasion, migration, and metastasis. Its expression has also been demonstrated in malignant melanoma, but not in other benign skin lesions, which has raised the possibility of using it as a predictive and prognosis marker. Its relationship with sentinel lymph node biopsy, however, has not been explored yet. A retrospective study including 120 histological samples of patients diagnosed with malignant cutaneous melanoma in Granada, between 2012 and 2018, was developed. All patients had had a sentinel lymph node biopsy (SLNB) performed at Hospital Universitario San Cecilio. IMP3 immunostaining was simultaneously carried out in the cutaneous lesion. We observed a significant difference regarding the percentage of cells expressing IMP3 (29.73 ± 3.81 for negative SLNB vs 44.86 ± 5.91 for positive SLNB, P = .020). Our endpoint calculated according to the ROC curve of 35% was significant with P = .007. H (P = .013) and AR (P = .016) indexes, created by the percentage of positive tumor cells and the intensity of the IMP3 expression, were also statistically significant. The most optimal cut-off points to predict the positivity of the SLNB were 35 for the percentage of positive tumor cells and 70 for the H score. We found a significant association between the expression of IMP3 and the regional nodal status defined by the SLNB on malignant melanomas in our series.

Giant lung metastasis of NRAS-mutant melanoma in a 24-year-old patient with a history of BRAF-mutant conventional melanoma harboring Spitzoid morphology: a case report

BackgroundSpitzoid melanocytic lesions represent a heterogeneous group of proliferations with ambiguous and overlapping terminology. The exact distinction of a Spitz nevus from a Spitzoid melanoma can be very difficult or, in some cases, impossible. Among the Spitzoid lesions, there is a lesion termed an atypical Spitz tumour (AST) that has intermediate histopathologic features between those of a Spitz nevus and a Spitzoid melanoma and thus uncertain malignant potential. There are several rare cases of patients with a Spitzoid melanoma initially misdiagnosed as a Spitz nevus or an AST with fatal consequences. It is, therefore, advised to perform a molecular characterization in cases where uncertain skin lesions are presented, as it may provide extended set of information with a possible impact on the treatment options. Furthermore, preventive measures, such as regular physical and skin examinations, as well as thorough scheduling of individual follow-up visits, are essential in patients with potentially malignant skin nevi.Case reportWe report a case of a young adult female with a history of AST excision with a negative sentinel lymph node biopsy (SLNB) and insufficient follow-up. Four years after the primary dermatological diagnosis, she presented with a giant tumour in the right hemithorax. Radical en bloc resection of the tumour with right pneumonectomy and resection of the pericardium with reconstruction of the pericardium using mesh was performed. A definitive histopathological examination revealed a metastatic melanoma. The association of the previously diagnosed AST and subsequent appearance of melanoma metastases led to a retrospective re-evaluation of the initial lesion. The suspected diagnosis of Spitzoid melanoma, however, was not confirmed. Moreover, the molecular examination revealed a major discordance between the initial lesion and the lung tumour, which most likely excluded the possible association of the lung metastasis with the initial skin lesion. The initial skin lesion was a BRAF-mutant melanoma with Spitzoid features and termed as AST, while the giant lung metastasis was NRAS-mutant melanoma. The subsequent postoperative course was complicated by the appearance of brain metastases that were stereotactically irradiated. Nevertheless, despite complex specialised medical care, the patient’s clinical condition rapidly deteriorated. By this time, no active oncological treatment was possible. The patient was delegated to local hospice for palliative care six months after the surgery and died three weeks later.ConclusionsOur patient was surgically treated at the age of 20 for AST and died four years later of metastatic NRAS-mutant melanoma most likely of different occult origin. Molecular characterization, as well as the close clinical follow-up should be always precisely performed in patients with uncertain skin lesions, such as AST.

Lack of distinct molecular profile of Primary Dermal Melanoma

Primary dermal melanoma (PDM) is a rare variant of melanoma which simulates metastatic melanoma to the skin. Diagnosis of PDM cannot be established on histologic grounds alonebut requires absence of evidence of melanoma elsewhere by clinical history and/or imaging studies. Despite this entity being clinically well documented, limited data on molecular characterization are available. We performed comprehensive mutation and copy number variation analysis in a series of PDMs in search for distinctive molecular features.Studies were approved by respective institutional review boards. Six cases fulfilling strict histologic criteria of PDM were identified in patients with absent history of melanoma elsewhere, negative sentinel lymph node biopsies and imaging studies. DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissue, and five cases passed quality control measures and were subjected to targeted exon sequencing using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets 410 panel. Two of five PDM carried NRAS hotspot mutations characteristic of cutaneous melanoma (CM) genomic subtypes. One case showed a probable low-activating NRAS mutation in combination with additional aberrations in other mitogen-activated protein kinase (MAPK) pathway effectors. Hotspot mutations were also identified in the TERT promoter region, and one tumor showed a mutation in the SWI/SNF remodeling complex. No oncogenic mutations were identified in one case. Furthermore, none of the tumors analyzed showed activating mutations in Gα subunits, including GNAQ and GNA11. Copy number alterations included deletions of Chr 9p, characteristic of CM.Despite PDM showing mutational heterogeneity, our findings suggest predominance of MAPK pathway aberrations in agreement with the mutational profile of CMs in general. Given the absence of genetic overlap with other distinct primary dermal melanocytic proliferations, mutational profiling will unlikely aid in the difficult differential diagnosis of PDM versus melanoma metastasis. Thorough metastatic workup remains crucial in establishing this rare diagnosis.

Lymphatic Transport Efficiency Determines Metastatic Potential of Cutaneous Melanoma.

BackgroundIn staging patients with clinical stage I-II melanoma, the sentinel lymph node (SLN) is the most important prognostic indicator; however, the false negative rate of SLN biopsy (SLNB) is 15%.MethodsNine patients with clinical Stage I-II melanoma underwent SLNB with repeated intraoperative radiotracer measurements to determine lymphatic transport efficiency (LTE), which was correlated with clinicopathologic data.ResultsLTE demonstrated the potential to predict SLN status. LTE in patients with occult nodal metastasis is 40 times faster than those with negative SLNBs. There was no confounding of LTE by clinicopathologic factors.Significance:LTE may be a novel biomarker for metastasis, with transformative potential for personalized precision diagnostics of early-stage disease and improved patient survival.

Impact of sentinel lymph-node biopsy and FDG-PET in staging and radiation treatment of anal cancer patients

To assess the role of sentinel lymph-node biopsy (SLNB) and FDG-PET in staging and radiation treatment (RT) of anal cancer patients. This retrospective study was performed on 80 patients (male: 32, female: 48) with a median age of 60 years (39–89 years) with anal squamous cell carcinoma who were treated from March 2008 to March 2018 at the IRCCS San Raffaele Hospital. Patients without clinical evidence of inguinal LNs metastases and/or with discordance between clinical evidence and imaging features were considered for SLNB. FDG-PET was performed in 69/80 patients. Patients with negative imaging in inguinal region and negative SLNB could avoid RT on groin to spare inguinal toxicity. CTV included GTV (primary tumour and positive LNs) and pelvic ± inguinal LNs. PTV1 and PTV2 corresponded to GTV and CTV, respectively, adding 0.5 cm. RT dose was 50.4 Gy/28 fractions to PTV2 and 64.8 Gy/36 fractions to PTV1, delivered with 3DCRT (n = 24) or IMRT (n = 56), concomitant to Mitomycin-C and 5-FU chemotherapy. FDG-PET showed inguinal uptake in 21/69 patients (30%) and was negative in 48/69 patients (70%). Lymphoscintigraphy was performed in 11/21 positive patients (4 patients SLNB confirmed inguinal metastases, 6 patients false positive and 1 patient SLN not found), and in 29/48 negative patients (5/29 showed metastases, 23/29 true negative and 1 SLN not found). Sensitivity, specificity, positive and negative predictive value of FDG-PET were 62%, 79%, 40% and 82%, respectively. Median follow-up time from diagnosis was 40.3 months (range: 4.6–136.4 months): 69 patients (86%) showed a complete response, 10 patients (13%) a partial response, 1 patient (1%) a stable disease. Patients treated on groin (n = 54) versus not treated (n = 26) showed more inguinal dermatitis (G1–G2: 50% vs. 12%; G3–G4: 17% vs. 0%, p < 0.05). For patients treated on groin, G3–G4 inguinal dermatitis, stomatitis and neutropenia were significantly reduced with IMRT against 3DCRT techniques (13% vs. 36%, p = 0.10; 3% vs. 36%, p = 0.003; 8% vs. 29%, p = 0.02, respectively). SLNB improves the FDG-PET inguinal LNs staging in guiding the decision to treat inguinal nodes. IMRT technique significantly reduced G3-G4 toxicities when patients are treated on groin.

Identifying Risk Factors for Regional Recurrence in Early-Stage Breast Cancer with pT1-2 and Negative Sentinel Lymph Node Biopsy.

BackgroundDue to the low rate of regional recurrence (RR) in early-stage breast cancer with pT1-2 and negative sentinel lymph node biopsy (SLNB), no regional therapy is suggested for them. However, whether there is a subset of patients who were with high risk of regional failure and may benefit from regional treatment is still unknown. The current study was designed to identify the patients with high risk of RR, thereby providing clues for enhanced regional therapy.MethodsWe analyzed a total of 1124 breast cancer patients with pT1-2N0 from May 2004 to Dec 2014. All the patients were treated with breast-conservation surgery (BCS) and adjuvant whole-breast radiotherapy. The regional recurrence-free survival (RRFS), local regional recurrence-free survival (LRRFS), disease-free survival (DFS) and overall survival (OS) were assessed by using the Kaplan–Meier method. Cox proportional hazards regression was performed to detect factors in predicting the RRFS.ResultsIn multivariable analysis, both T stage and molecular type were significant predictors of RRFS. Patients with T2 stage had a lower RRFS than those with T1stage. Triple-negative patients were more likely to suffer regional failure than the patients with other molecular types. The two predictors were then employed to divide all the patients into three groups based on the risk level of RR. Patients with both T2 and triple-negative molecular type had the lower RRFS, LRRFS, DFS and OS than the patients with one or no risk factor.ConclusionFor early-stage breast cancer patients with negative SLNB, those who were with both T2 stage and triple-negative molecular type had a high rate of RR and enhance regional therapy may be needed for them.

Challenges and outcomes in establishing a sentinel lymph node biopsy service for oral squamous cell carcinoma in a regional district specialist hospital

UK national guidelines in 2016 recommended that sentinel lymph node biopsy (SLNB) should be offered to patients with early oral squamous cell carcinoma (OSCC). We review the establishment of an OSCC SLNB service with specific consideration to resources, service implications and patient outcomes. A review of processes was performed to identify key stages in establishing the service, and subsequently a retrospective cohort study consisting of 46 consecutive patients with T1/T2 N0 OSCC was undertaken. The key stages identified were: coordinating a nuclear medicine pathway and reliable cost-appropriate pathology service, constructing a Trust business case, and gaining approval of a new interventional service policy. A median (range) of 3.3 (1-8) sentinel nodes (SLN) were removed, with 17 patients having a positive SLN. The negative predictive value of SLNB was 100%, with 12 having a SLN outside the field if elective neck dissection (END) was planned. There was a significantly increased risk of a positive SLN with increasing depth of invasion (DOI) (p=0.007) and increased diameter (p=0.036). We also identified a longer-than-ideal time to completion neck dissection and inadequate ultrasound follow up of negative SLNB patients. Establishment of a service requires careful planning. Our results were in keeping with those reported in the literature, and showed that SLNB for OSCC has a high negative predictive value and can identify at-risk SLN outside the traditional END levels, even in well-lateralised tumours. Our findings show that DOI and size of SLN were significantly associated with a positive SLN, and also identified areas requiring improvement.