Prognostic significance of sentinel lymph node biopsy in elderly with cutaneous melanoma: systematic review and meta-analysis.

Sentinel lymph node biopsy is the most powerful prognostic indicator to date for cutaneous melanoma. Even though elderly patients have a lower incidence of sentinel node involvement, its results are still necessary for access to adjuvant therapies. This is highly relevant considering that the Western population shows an aging trend, and the incidence of melanoma has grown exponentially over the years, making elderly patients more likely to die from melanoma than younger ones. We performed a systematic review to investigate the prognostic significance of sentinel lymph node biopsy in elderly patients with melanoma. The systematic review was conducted following the PRISMA guidelines and registered in PROSPERO. The authors searched the Cochrane Database, EMBASE, PubMed, and WOS. Eligible studies for the systematic review were clinical trials, observational population studies, clinical or hospital-based cohort studies, and case-control studies. The meta-analysis was conducted using the R software program applying the meta package. Six reports were identified to meet the inclusion criteria. All studies were retrospective, non-randomized cohorts. The results obtained in this systematic review show a statistically significant influence of sentinel lymph node biopsy on disease-specific survival (HR = 2.87; 95% CI: 1.73-4.74) but also suggest that a positive result negatively impacts disease-free survival (HR = 3.41; 95% CI: 0.96-12.11). This meta-analysis shows that a positive sentinel lymph node biopsy does not imply differences in overall survival but significantly influences disease-specific survival and suggests an unfavorable impact on disease-free survival.

Recurrence factors in patients with cutaneous melanoma and positive sentinel lymph node treated in a single reference unit in Buenos Aires.

INTRODUCTION: Although therapeutic advances have improved results of cutaneous melanoma (CM), sentinel node-positive patients still have substantial risk to develop recurrent disease. We aim to investigate prognostic indicators associated with disease recurrence in positive-sentinel lymph node biopsy (SLNB) patients in a Latin-American population. METHODS: Retrospective analysis of CM patients and positive-SLNB (2010-2020). Patients were divided into two groups: Group A (completion lymph node dissection, CLND), Group B (active surveillance, AS). Association of demographics, tumor data and SLN features with recurrence-free (RFS), distant metastases-free (DMFS) and melanoma specific (MSS) survival was analyzed. RESULTS: Of 205 patients, 45 had a positive SLNB; 27(60%) belonged to Group A and 18(40%) to Group B. With a median follow-up of 36 months, 16 patients (12 in Group A and 4 in Group B) developed recurrent disease and estimated 5-yr RFS at any site was 60% (CI95%, 0.39 - 0.77) (44.5% in CLND group vs. 22% in AS group; P = 0.20). Estimated 5-yr DMFS and MSS: 65% (CI 95%, 0.44 - 0.81) and 73% (CI 95%, 0.59 - 0.89) with no differences between groups (p = 0.41 and 0.37, respectively). Independent predictors of poorer MSS were extranodal extension (ENE) and MaxSize > 2 mm of melanoma deposit in SLN. Factors independently associated with DMFS: Breslow depth > 2 mm, ENE, number (≥ 2) of positive SN and CLND status. CONCLUSION: Primary tumor and SN features in melanoma provide important prognostic information that help optimize prognosis and clinical management. AS is now the preferred approach for most positive-SLNB CM patients.

Introducción: Si bien los avances terapéuticos han permitido mejorar los resultados del melanoma cutáneo (MC), los pacientes con ganglio centinela positivo (BGCP) aún tienen riesgo elevado de desarrollar recurrencia de la enfermedad. Nuestro objetivo fue investigar indicadores pronósticos asociados a dicho evento en una población latinoamericana. Métodos: Análisis retrospectivo de pacientes con MC y BGCP entre 2010-2020. Los pacientes se dividieron en 2 grupos: Grupo A (linfadenectomía terapéutica) y Grupo B (Vigilancia activa, VA). Se analizaron datos demográficos, tumorales y características del GC junto con sobrevidalibre de recurrencia (SLR), libre de metástasis a distancia (SLMD) y específica de melanoma (SEM). Resultados: De 205 pacientes, 45 presentaron BGCP; 27 (60%) perteneció al Grupo A y 18 (40%) al Grupo B. Con una mediana de seguimiento de 36 meses, 16 pacientes (12 en Grupo A y 4 en Grupo B) desarrollaron enfermedad recurrente con una SLR a 5 años de 60% (IC95%: 0.39-0.77) (44.5% en Grupo B vs. 22% en Grupo A; P = 0.20). Las SLMD y SEM estimadas a 5 años fueron de 65% (CI 95%, 0.44 ­ 0.81) y 73% (CI 95%, 0.59 ­ 0.89) sin diferencias entre ambos grupos (p = 0.41 y 0.37, respectivamente). Los predictores independientes de peor SEM fueron: extensión extranodal (ENE) y MaxSize > 2mm de depósito tumoral en GC. Los factores asociados de forma independiente con SLMD fueron Breslow > 2mm, ENE, número (≥ 2) de GC positivos y el status (positividad) de la linfadenectomía. Conclusión: Características del tumor primario y del GC brindan información importante que ayuda a optimizar el pronóstico y manejo clínico de los pacientes con MC. La VA es actualmente el abordaje de elección para la mayoría de los pacientes con BGCP.

Melanoma Registry of the Spanish Academy of Dermatology and Venereology (REGESMEL): Description and Data in its First Year of Operation. / Registro de Melanoma de la Academia Española de Dermatología y Venereología (REGESMEL): descripción y datos en el primer año de funcionamiento.

INTRODUCTION: The incidence of melanoma is rising in Spain. The prognostic stages of patients with melanoma are determined by various biological factors, such as tumor thickness, ulceration, or the presence of regional or distant metastases. The Spanish Academy of Dermatology and Venereology (AEDV) has encouraged the creation of a Spanish Melanoma Registry (REGESMEL) to evaluate other individual and health system-related factors that may impact the prognosis of patients with melanoma. The aim of this article is to introduce REGESMEL and provide basic descriptive data for its first year of operation. METHODS: REGESMEL is a prospective, multicentre cohort of consecutive patients with invasive cutaneous melanoma that collects demographic and staging data as well as individual and healthcare-related baseline data. It also records the medical and surgical treatment received by patients. RESULTS: A total of 450 cases of invasive cutaneous melanoma from 19 participant centres were included, with a predominance of thin melanomas≤1mm thick (54.7%), mainly located on the posterior trunk (35.2%). Selective sentinel lymph node biopsy was performed in 40.7% of cases. Most cases of melanoma were suspected by the patient (30.4%), or his/her dermatologist (29.6%). Patients received care mainly in public health centers (85.2%), with tele-dermatology resources being used in 21.6% of the cases. CONCLUSIONS: The distribution of the pathological and demographic variables of melanoma cases is consistent with data from former studies. REGESMEL has already recruited patients from 15 Spanish provinces and given its potential representativeness, it renders the Registry as an important tool to address a wide range of research questions.

Feasibility of Omitting Sentinel Lymph Node Biopsy in an Under-screened Cohort of Breast Cancer Patients With a Premastectomy Diagnosis of Ductal Carcinoma In Situ.

BACKGROUND: Nodal involvement in ductal carcinoma in situ (DCIS) is rare. In patients with DCIS diagnosis prior to mastectomy, a sentinel lymph node biopsy (SLNB) is usually performed during mastectomy, to avoid the risk of reoperation and the non-identification of SLN subsequently, should there be an upgrade to invasive cancer. We aimed to study the feasibility of omitting SLNB in an under-screened cohort, with mostly symptomatic patients and DCIS diagnosis before mastectomy, by determining the upgrade rate to invasive cancer/ DCIS microinvasion (DCISM) and its associated risk factors. METHODS: Patients with pure DCIS diagnosis premastectomy were reviewed retrospectively. Patients with known DCISM or invasive cancer before mastectomy and bilateral cancers were excluded. Patients' demographics, radiological and pathological data premastectomy were analyzed. RESULTS: A total of 189 patients were included. The mean age was 53.8 (range: 29-85) years old. About 64.4% presented with symptoms. 36.0% and 15.3% upgraded to invasive cancer and DCISM on mastectomy respectively. Palpable tumor (P = .0036), large size on ultrasound (P = .0283), tumor seen on mammogram and ultrasound (P = .0082), ultrasound-guided biopsy (P < .0001), high-grade DCIS on biopsy (P = .0350) and no open biopsy/lumpectomy before mastectomy (P < .0001) were associated with the upgrade, with the latter factor remaining significant after multivariable analysis. Nodal involvement was 8.47% and was associated with invasive cancer (P < .0001). CONCLUSION: In a cohort who had DCIS diagnosis before mastectomy and were mostly symptomatic, the upgrade rate was 51.3%. Despite the high upgrade rate, nodal involvement remained comparable. Risk factors could select patients for omission of upfront SLNB, with a delayed SLNB planned if needed.

Accuracy of sentinel lymph node biopsy in male breast cancer: Systematic review and meta-analysis.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is commonly used in the surgical management of male breast cancer. Contrary to female breast cancer, limited data exist about its performance in male breast cancer. The objective of this systematic review and meta-analysis was to evaluate the SLNB accuracy in male breast cancer. METHODS: MEDLINE, EMBASE, Web of Science and The Cochrane Library were searched from January 1995 to April 2023 for studies evaluating the SLNB identification rate and false-negative rate in male breast cancer with negative preoperative axillary evaluation and primary surgery. For SLNB false-negative rate, the gold standard was the histology of axillary lymph node dissection (ALDN). Methodological quality was assessed by using the QUADAS-2 tool. Pooled estimates of the SLNB identification rate and false-negative rate were calculated. Heterogeneity of the pooled studies was evaluated using I2 index. RESULTS: A total of 12 retrospective studies were included. The 12 studies that reported the SLNB identification rate gathered a total of 164 patients; the 5 studies that reported the SLNB false-negative rate gathered a total of 50 patients with a systematic ALND. The pooled estimate of the SLNB identification rate was 99.0%. The SLNB false-negative rates were 0% in the 5 included studies and consequently so as the pooled estimate of the false-negative rate with no heterogeneity. CONCLUSION: SLNB for male breast cancer, following negative preoperative axillary assessment and primary surgery, appears feasible, consistent, and effective. Our research supports conducting immediate SLNB histological evaluation to facilitate prompt ALND in case of positive results.

Role of sentinel lymph node evaluation during hysterectomy for preoperative pathology diagnosis of endometrial intraepithelial neoplasia in a community hospital setting.

OBJECTIVE: To determine the utility of sentinel lymph node (SLN) evaluation during hysterectomy for endometrial intraepithelial neoplasia (EIN) in a community hospital setting and identify descriptive trends among pathology reports from those diagnosed with endometrial cancer (EC). METHODS: We reviewed patients who underwent hysterectomy from January 2015 to July 2022 for a pathologically confirmed diagnosis of EIN obtained by endometrial biopsy (EMB) or dilation and curettage. Data was obtained via detailed chart review. Statistical testing was utilized for between-group comparisons and multivariate logistic regression modeling. RESULTS: Of the 177 patients with EIN who underwent hysterectomy during the study period, 105 (59.3%) had a final diagnosis of EC. At least stage IB disease was found in 29 of these patients who then underwent adjuvant therapy. Pathology report descriptors suspicious for cancer and initial specimen type obtained by EMB were independently and significantly associated with increased odds of EC diagnosis (aOR 8.192, p < 0.001;3.746, p < 0.001, respectively). Operative times were not increased by performance of SLN sampling while frozen specimen evaluation added an average of 28 min to procedure length. Short-term surgical outcomes were also similar between groups. CONCLUSION: Patients treated for EIN at community-based institutions might be more likely to upstage preoperative EIN diagnoses and have an increased risk of later stage disease than previous research suggests. Given no surgical time or short-term outcome differences, SLN evaluation should be more strongly considered in this practice setting, especially for patients diagnosed by EMB or with pathology reports indicating suspicion for EC.

Macroscopic tumor dimension, sentinel lymph node outcome, and survival analysis among cutaneous melanoma.

BACKGROUND: Cutaneous melanoma is characterized by a high risk of metastasis to distant organs and a substantial mortality rate. For planning treatment and assessing outcomes, the Breslow micrometric measurement is critical. The tumor macroscopic dimension is not considered a prognostic parameter in cutaneous melanoma, although there are studies showing that tumor size is an independent prognostic factor for melanoma-specific survival. Therefore, this study aimed to evaluate the macroscopic dimension of melanoma and other known prognostic factors (i.e., Breslow index, mitoses, regression, and ulceration) as predictors of sentinel lymph node outcome and survival outcome. METHODS: We performed a retrospective cross-sectional study of 227 melanoma lesions subjected to sentinel lymph node biopsy at two Brazilian referral centers. RESULTS: On univariate analysis, there was a statistically significant correlation between the largest macroscopic tumor dimension and the sentinel lymph node result (P = 0.001); however, on multivariate analysis considering all evaluated parameters, there was no significant difference between the sentinel lymph node result and the tumor macroscopic dimension (P = 0.2689). Regarding melanoma-specific survival, the macroscopic dimension showed no significant correlation (P = 0.4632) in contrast to Breslow's dimension (P < 0.0001). CONCLUSION: The Breslow thickness was the only significant factor related to both the sentinel lymph node outcome and melanoma specific survival among the evaluated variables.

Ganglio centinela positivo en melanoma: factores predictivos y resultados del vaciamiento ganglionar / Positive sentinel lymph node in melanoma: predictive factors and results of completion lymph node dissection

RESUMEN Antecedentes: la biopsia del ganglio centinela (GC) es la técnica aceptada para determinar el pronóstico en estadios iniciales de melanoma cutáneo. La ventaja del vaciamiento ganglionar (VG) cuando el GC resulta positivo ha sido recientemente cuestionada. Objetivo: describir los porcentajes y factores asociados a metástasis en el GC, y en los ganglios no centinela (GnC) en los VG de pacientes con GC positivo. Material y métodos: se llevó a cabo un estudio retrospectivo de los registros clínicos y patológicos de 139 pacientes operados por melanoma cutáneo entre enero de 2012 y diciembre de 2019. Resultados: a 96 (69%) pacientes se les realizó biopsia de GC. El promedio de edad fue 61,7 años ± 17,5 (19-93); 53 (55,2%) fueron hombres. La lesión primaria estuvo ubicada en: extremidades 47 (49%), tronco 39 (40,6%), cabeza y cuello 10 (10,4%). El promedio de espesor de Breslow fue 5,01 mm (1,05- 50 mm) y se encontró ulceración en 35 casos (36,4%). El GC fue identificado en todas las oportunidades y en 39 (40,6%) fue positivo. Hubo asociación con el espesor ≥ 3 mm (p = 0,000017) y con la ulceración (p = 0,0011). A los pacientes con GC positivo se les efectuó el VG del territorio afectado: 23 axilar, 10 inguinal y 6 cervical. Veintitrés (59%) presentaron metástasis en GnC. Se asoció con el espesor (p = 0,022) y la ulceración (p = 0,019). Conclusión: existió un alto porcentaje de GnC positivos en la población estudiada, vinculado al espesor y la ulceración. Estas características, así como la dificultad de un estricto seguimiento, inducen a no abandonar el VG en pacientes con GC positivo.

ABSTRACT Background: Sentinel lymph node (SLN) biopsy is the technique accepted to determine the prognosis of early cutaneous melanomas. The advantage of lymph node dissection (LND) when SLN biopsy is positive has recently been questioned. Objective: The aim of this study is to describe the percentages and factors associated with SLN and non-sentinel node (NSN) metastases in LNDs of SLN-positive patients. Material and methods: The clinical records and pathology reports of 139 patients undergoing surgery for cutaneous melanoma between January 2012 and December 2019 were retrospectively reviewed. Results: Ninety-six (69%) patients underwent SLN biopsy. Mean age was 61.7 ± 17.5 years (19-93) and 53 (55.2%) were men. The primary lesion was located in the extremities in 47 (49%) cases, in the trunk in 39 (40.6%), and in the head and neck in 10 (10.4%). Mean Breslow thickness was 5.01 mm (1.05-50 mm) and ulceration was found in 35 cases (36.4%). The SLN was identified in all the cases and was positive in 39 (40.6%). There was an association with thickness ≥ 3 mm (p = 0.000017) and ulceration (p = 0.0011). Those patients with positive SLN biopsy underwent LND of the territory involved: axillary in 23, inguinal in 10 and cervical in 6. Twenty-three (59%) presented NSLN metastases and were associated with thickness (p = 0.022) and ulceration (p = 0.019). Conclusion: There was a high percentage of positive NSLN in the population studied which was associated with thickness and ulceration. These characteristics and the difficulty to achieve strict follow-up are the reasons for completion LND in SLN-positive patients.

No axillary surgical treatment for lymph node-negative patients after ultra-sonography [NAUTILUS]: protocol of a prospective randomized clinical trial.

BACKGROUND: Following sentinel lymph node biopsy (SLNB), the axillary recurrence rate is very low although SLNB has a false-negative rate of 5-10%. In the ACOSOG Z0011 trial, non-sentinel positive-lymph nodes were found in more than 20% of the axillary dissection group; the SLNB only group did not have a higher axillary recurrence rate. These findings raised questions about the direct therapeutic effect of the SLNB. SLNB has post-surgical complications including lymphedema. Considering advances in imaging modalities and adjuvant therapies, the role of SLNB in early breast cancer needs to be re-evaluated. METHODS: The NAUTILUS trial is a prospective multicenter randomized controlled trial involving clinical stage T1-2 and N0 breast cancer patients receiving breast-conserving surgery. Axillary ultrasound is mandatory before surgery with predefined imaging criteria for inclusion. Ultrasound-guided core needle biopsy or needle aspiration of a suspicious node is allowed. Patients will be randomized (1:1) into the no-SLNB (test) and SLNB (control) groups. A total of 1734 patients are needed, considering a 5% non-inferiority margin, 5% significance level, 80% statistical power, and 10% dropout rate. All patients in the two groups will receive ipsilateral whole-breast radiation according to a predefined protocol. The primary endpoint of this trial is the 5-year invasive disease-free survival. The secondary endpoints are overall survival, distant metastasis-free survival, axillary recurrence rate, and quality of life of the patients. DISCUSSION: This trial will provide important evidence on the oncological safety of the omission of SLNB for early breast cancer patients undergoing breast-conserving surgery and receiving whole-breast radiation, especially when the axillary lymph node is not suspicious during preoperative axillary ultrasound. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04303715 . Registered on March 11, 2020.

Trends in Sentinel Lymph Node Biopsies in Patients With Inflammatory Breast Cancer in the US.

Importance: The standard of care for inflammatory breast cancer (IBC) is neoadjuvant chemotherapy, total mastectomy with axillary lymph node dissection (ALND), and postmastectomy radiation therapy. Existing studies suggest that sentinel lymph node biopsy (SLNB) may not be reliable in IBC. The use and frequency of SLNB in women with IBC is not well characterized. Objective: To determine the frequency and temporal trend of SLNB in patients with IBC. Design, Setting, and Participants: This retrospective cohort study used the National Cancer Database, a nationwide hospital-based cancer registry, and included women who were diagnosed with nonmetastatic IBC and underwent axillary surgery from 2012 to 2017. Data were analyzed from January 2021 to May 2021. Exposures: Any SLNB, including SLNB alone and SLNB followed by ALND, and ALND alone. Main Outcomes and Measures: Scatterplot fit with a linear regression model were used to evaluate the yearly increase of any SLNB use. Multivariable logistic regression models to evaluate the association of study variables with the outcome of any SLNB. Results: This study included a total of 1096 women (mean [SD] age, 56.1 [12.9] years) who were 18 years or older with nonmetastatic IBC diagnosed between 2012 and 2017. Of the 186 of 1096 women (17%) who received any SLNB, 137 (73.7%) were White individuals; and of the 910 of 1096 women (83%) who received an ALND only, 676 (74.3%) were White individuals. Among women undergoing any SLNB, 119 of 186 (64%) did not undergo a completion ALND. There was a statistically significant increasing trend in the use of SLNB from 2012 to 2017 (22 of 205 patients [11%] vs 32 of 148 patients [22%]; P = .004). In multivariable analysis, the use of SLNB was associated with diagnosis year (2017 vs 2012; odds ratio [OR], 2.26; 95% CI, 1.26-4.20), clinical nodal status (cN3 vs 0; OR, 0.39; 95% CI, 0.22-0.67), and receipt of reconstructive surgery (OR, 1.80; 95% CI, 1.09-2.96). Conclusions and Relevance: The findings of this cohort study suggest that there is frequent and increasing use of SLNB in patients with IBC that is not evidence-based or supported by current treatment guidelines.

Sentinel lymph node biopsy alone in the management of early cervical carcinoma.

OBJECTIVE: Sentinel lymph node (SLN) biopsy aims to assess lymph node status with reduced surgical morbidity. The aim of the study was to determine the accuracy and safety of SLN biopsy in the management of early cervical carcinoma using a double technique (technetium-99m (Tc-99m) nanocolloid and methylene blue dye injection). METHODS: This was a 10-year study from January 2009 to January 2019 that recruited 103 consecutive women undergoing surgery for early cervical carcinoma, FIGO 2009 stage IA1 (grade 3, and grade 2 with lymphovascular space invasion) to IB1 (<2 cm), at the West Kent Gynaecological Oncology Centre, Maidstone, UK. All patients were given the choice of pelvic node dissection and SLN mapping or SLN only. All patients elected to undergo SLN only. In total 97 patients had SLN mapping performed laparoscopically. We used the combined method (Tc-99m nanocolloid and/or methylene blue dye). All SLN routinely underwent ultrastaging. RESULTS: At least one SLN was detected in all 103 patients, using at least one of the combined methods (Tc-99m nanocolloid or blue dye). Bilaterally SLN were removed in 85/103 women with an 83% bilateral detection rate. The median SLN count was 2.3 (range 1-6) nodes. Of 103 patients, 7 (6.7%) patients had lymph node involvement. There were no pelvic or para-aortic lymph node recurrences with a median follow-up of 53 (range 8-120) months. The specificity and negative predictive value of a negative SLN was 100%. None of our 103 patients reported lower extremity lymphedema. CONCLUSION: In carefully selected patients with early cervical carcinoma, SLN biopsy alone appears to be a safe method for lymph node assessment of women undergoing surgical staging. Ultrastaging is an essential part of histologic examination of SLN.

Long-term oncological safety of sentinel lymph node biopsy in early-stage cervical cancer: A post-hoc analysis of SENTICOL I and SENTICOL II cohorts.

OBJECTIVES: To compare oncologic outcomes of patients with early-stage cervical cancer and negative nodes who underwent sentinel lymph node biopsy alone (SLNB) versus pelvic lymphadenectomy (PL). METHODS: An ancillary analysis of two prospective multicentric trials on SLN biopsy for cervical cancer (SENTICOL I and II) was conducted. Only patients with early-stage cervical cancer (IA to IIA FIGO stage), bilateral detection of SLN, negative SLN after ultrastaging and negative non-SLN after final pathologic examination were included. Risk-factors of recurrence and disease-specific mortality were determined by Cox proportional hazard models. RESULTS: Between January 2005 and July 2012, 259 node-negative patients were analyzed: 87 in the SLNB group and 172 in the PL group. The median follow-up was 47 months [4-127]. During the follow-up, 21 patients (8.1%) experienced recurrences, including 4 nodal recurrences (1.9%), and 9 patients (3.5%) died of cervical cancer. Disease-free survival (DFS) and disease-specific survival (DSS) were similar between SLNB and PL groups, 85.1% vs. 80.4%, p = 0.24 and 90.8% vs. 97.2%, p = 0.22 respectively. By Cox multivariate analysis, SLNB compared to PL was not associated with DFS (HR = 1.78, 95%CI = [0.71-4.46], p = 0.22) neither with DSS (HR = 3.02, 95%CI = [0.69-13.18], p = 0.14). Only pathologic risk level according to the Sedlis criteria was an independent predictor of DFS and DSS. CONCLUSIONS: Omitting full pelvic lymphadenectomy for patients with bilateral negative SLN does not seem to be associated with an increased risk of recurrence in this series. Survival non-inferiority needs to be confirmed by prospective trials.

Risk factors for lymphedema after breast surgery: A prospective cohort study in the era of sentinel lymph node biopsy.

INTRODUCTION: The Objective was to investigate the incidence of lymphedema after breast cancer treatment and to analyze the risk factors involved in a tertiary level hospital. METHODS: Prospective longitudinal observational study over 3 years post-breast surgery. 232 patients undergoing surgery for breast cancer at our institution between September 2013 and February 2018. Sentinel lymph node biopsy (SLNB) or axillary lymphadenectomy (ALND) were mandatory in this cohort. In total, 201 patients met the inclusion criteria and had a median follow-up of 31 months (range, 1-54 months). Lymphedema was diagnosed by circumferential measurements and truncated cone calculations. Patients and tumor characteristics, shoulder range of motion limitation and local and systemic therapies were analyzed as possible risk factors for lymphedema. RESULTS: Most cases of lymphedema appeared in the first 2 years. 13.9% of patients developed lymphedema: 31% after ALND and 4.6% after SLNB (p < 0.01), and 46.7% after mastectomy and 11.3% after breast-conserving surgery (p < 0.01). The lymphedema rate increased when axillary radiotherapy (RT) was added to radical surgery: 4.3% for SLNB alone, 6.7% for SLNB + RT, 17.6% for ALND alone, and 35.2% for ALND + RT (p < 0.01). In the multivariate analysis, the only risk factors associated with the development of lymphedema were ALND and mastectomy, which had hazard ratios (95% confidence intervals) of 7.28 (2.92-18.16) and 3.9 (1.60-9.49) respectively. CONCLUSIONS: The main risk factors for lymphedema were the more radical surgeries (ALND and mastectomy). The risk associated with these procedures appeared to be worsened by the addition of axillary radiotherapy. A follow-up protocol in patients with ALND lasting at least two years, in which special attention is paid to these risk factors, is necessary to guarantee a comprehensive control of lymphedema that provides early detection and treatment.

Is image-guided core needle biopsy of borderline axillary lymph nodes in breast cancer patients clinically helpful?

BACKGROUND: When borderline axillary lymph nodes (bALN) are identified on ultrasound (US) for breast cancer (BC) patients, preoperative management is unclear. We aimed to evaluate if core needle biopsy (CNB) for bALN is clinically helpful or disruptive. METHODS: Retrospective review of BC patients with bALN from 2014 to 2019 was performed. Clinicopathologic data were compared for those who did and did not have CNB. RESULTS: CNB (n = 34) and no CNB (n = 31) were similar with respect to clinicopathologic factors. Surgical LN-positive rate was the same between cohorts (p = 0.26). CNB was disruptive in 58.8 %; all had CNB for pN0 disease. CNB was helpful in 34.2 %: 14.7 % proceeded directly to axillary dissection; 17.6 % had positive LN localized after neoadjuvant chemotherapy. CONCLUSIONS: CNB for bALN is more likely clinically disruptive and did not impact surgical LN positive rate. BC patients with bALN should undergo CNB only if it will change clinical management.

Sentinel lymph node biopsy for stage II endometrial cancer: Recent utilization and outcome in the United States.

OBJECTIVE: To examine trends and outcomes related to sentinel lymph node (SLN) biopsy for stage II endometrial cancer. METHODS: This is a retrospective observational cohort study querying the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The study population was 6,314 women with T2 endometrial cancer who underwent hysterectomy from 2010-2018. Exposure allocation was based on nodal evaluation type: lymphadenectomy (LND; n=4,915, 77.8%), SLN biopsy (n=340, 5.4%), or no surgical nodal evaluation (n=1,059, 16.8%). The main outcomes were (i) trends and characteristics related to nodal evaluation assessed by multinomial regression, and (ii) overall survival (OS) assessed by an inverse probability of treatment weighting propensity score analysis. A sensitivity analysis was performed to examine concurrent LND in women who underwent SLN biopsy. RESULTS: The utilization of SLN biopsy increased from 1.6% to 16.1%, while the number of LND decreased from 81.5% to 65.7% between 2010-2018 (P<0.05). In multivariable analysis, the utilization of SLN biopsy increased 45% annually (adjusted-odds ratio 1.45, 95% confidence interval [CI] 1.37-1.54, P<0.001). The frequency of SLN biopsy alone exceeded the frequency of SLN biopsy with concurrent LND in 2017 (6.8% versus 3.4%), followed by continued increase in SLN biopsy alone (11.2% versus 4.9%) in 2018. In the weighted model, the 3-year OS rate was 79.9% for the SLN biopsy group and 78.6% for the LND group (hazard ratio 0.98, 95%Cl 0.80-1.20, P=0.831). Similarly, the SLN biopsy alone without concurrent LND had comparable OS compared to the LND group (hazard ratio 0.90, 95%CI 0.59-1.36, P=0.615). CONCLUSION: Utilization of SLN biopsy in stage II endometrial cancer increased significantly over time, and SLN biopsy-incorporated nodal assessment was not associated with worsened short-term survival outcome.

Rates of Upstaging, Between Diagnosis and Surgery, and Clinical Management of Metastatic Cutaneous Squamous Cell Carcinoma: A Case-Control Study.

BACKGROUND: Cutaneous squamous cell carcinomas (cSCC) have upstage rates of approximately 10.3% to 11.1%. Data are currently limited on the rate of upstaging for metastatic cSCC. OBJECTIVE: The aim of this study was to determine the rates of upstaging, between diagnosis and surgery, and differences in management for metastatic and non-metastatic high-risk cSCC. MATERIALS AND METHODS: This was a retrospective, case-control, single institution, multi-center study. Univariate analysis was used. RESULTS: Sixty-eight subjects (34 metastatic & 34 non-metastatic) with 69 tumors were included. The overall rate of upstaging was 46.4%. The most common reasons for upstage were undocumented tumor size and under-diagnosis of poor differentiation. There were no differences in rates of upstaging. Preoperative imaging was performed in 43.6% of wide local excisions (WLE) versus 3.3% of Mohs micrographic surgery (MMS; p < .001). The median days from surgery to sentinel lymph node biopsy (SLNB), or nodal dissection was shorter for WLE versus MMS (0 vs 221 days, p < .001). CONCLUSION: Improved clinical documentation, including documenting tumor size, and the identification of pathologic risk factors, including poor differentiation and depth of invasion, are needed for proper staging. Preoperative imaging and discussion of SLNB may be beneficial for high-risk T2b and T3 tumors.

Does failed mapping predict sentinel lymph node metastasis in cN0 breast cancer?

Aims: The clinical significance of nonvisualized sentinel lymph nodes (non-vSLNs) is unknown. The authors sought to determine the incidence of non-vSLNs on lymphoscintigraphy, the identification rate during surgery, factors associated with non-vSLNs and related axillary management. Patients & methods: A total of 30,508 consecutive SLN procedures performed at a single institution from 2000 to 2017 were retrospectively studied. Associations between clinicopathological factors and the identification of SLNs during surgery were assessed. Results: Non-vSLN occurred in 525 of the procedures (1.7%). In 73.3%, at least one SLN was identified intraoperatively. Nodal involvement was only significantly associated with SLN nonidentification (p < 0.001). Conclusion: Patients with non-vSLN had an increased risk for SLN metastasis. The detection rate during surgery was consistent, reducing the amount of unnecessary axillary dissection.

Lay abstract To study the clinical significance of nonvisualized sentinel lymph nodes (non-vSLNs) in axillary surgery for breast cancer, 30,508 consecutive SLN procedures performed at a single institution from 2000 to 2017 were retrospectively reviewed with the aim to analyze the incidence of non-vSLNs on lymphoscintigraphy, the identification rate during surgery, factors associated with non-vSLNs and related axillary management. Associations between clinicopathological factors and the identification of SLNs during surgery were assessed. Non-vSLN occurred in 525 of the procedures (1.7%). In 73.3%, at least one SLN was identified intraoperatively. Nodal involvement was only significantly associated with SLN nonidentification (p < 0.001). Patients with non-vSLN had an increased risk for SLN metastasis. The detection rate during surgery was consistent, reducing the amount of unnecessary axillary dissection.

Data Driven for Early Breast Cancer Staging using Integrated Mammography and Biopsy.

OBJECTIVE: Breast cancer patients who have a rapid diagnosis have been better prognosis than late diagnosis. The popular screening is mammogram or ultrasound. In recent years, researchers try to develop data driven models to predict early cancer staging from the first screening. However, data elements are not complete such as lymph node status. Therefore, the Integrated dataset approach will be challenging. METHODS: Because the data elements are not collected from the same source, joining between mammography and biopsy data were performed using latent variables that determine by tumor severity. The datasets consist of 445 mammography reports and 183 pathological reports. The latent variables of the mammogram dataset were determined by the severity of mass, while latent variables of the pathological dataset were determined by TNM Staging. The latent variables were used to join between two datasets. Then, the prediction models were built using the machine learning technique. The modeling is divided into three steps; staging prediction, lymph node prediction, and prognosis. RESULTS: Integrated dataset from mammography and biopsy extend more factors and built the models to predict breast cancer staging in the mammography process. The staging prediction is 100% accuracy. The lymph node prediction are 72.47% accuracy, 73.94% specificity, and 72.5% sensitivity. An area under ROC curve is 0.74. The prognosis model prediction are 72.72% accuracy, 80% specificity, and 77% sensitivity. An area under ROC curve is 0.87. There are also built the rule for early staging, diagnosis, and prognosis.  Conclusion: This study aims to build the models for early staging, diagnosis, and prognosis using the less aggressive method. The advantages are (1) predict staging from the first screening (2) estimate the lymph node metastases for planning to ALND or SLNB (3) evaluate overall survival time. These advantages help the physician planning the best treatment for cancer patients.

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.

Usefulness of histological superstudy of sentinel lymph nodes detected with radioisotopes in colon cancer.

INTRODUCTION: Adjuvant chemotherapy (CT) significally reduces the rate of relapse in +pN (stage III) colon cancer (CC) and in some pN0 (stage II) with risk factors such as pT4, vascular invasion V1, perineural invasion Pn1, and complicated tumors. However, unexpectedly, 20%-30% of pN0 present a relapse in the follow-up, which may suggest that the lymph node involvement was not discovered in the conventional histological study (CS), and its finding with a superstudy (SS) could increase the number of patients who would benefit from neoadjuvant CT. It is not possible to perform this SS in every lymph node (LN) from the specimen, but it is possible in a small group of LN which are representative of the N status (definition of sentinel node SN). The aim of our work is to state the representativeness of the SN and to analyze de number of patients who are suprastaged after the SS of the SN. MATERIAL AND METHODS: Prospective study of a series of patients who have undergone curative surgery for CC, to whom we perform selective biopsy of sentinel node (SBDN). Identification of SN was carried out with in vivo injection of the radiotracer, with ex vivo isolation of SN. Once the specimen is out, we take pictures of the surgical bed to rule out the presence of aberrant drainage routes, out of the routine oncological resection area. We performed the histological CS (Hematoxilin-Eosin stain (H-E) in conventional sections) in the rest of the LN from the mesocolon. In the SN we performed the CS and a SS with H-E in serial sections, immunohistochemistry (IHC) and molecular study with OSNA® (One Step Nucleic Acid Amplification). Diagnostic validity study od SBSN was carried out, defining the false negative (FN) as the negativity of the SN while other LN are positive (N+), as well as a valuation of the suprastaging due to the SS of the SN. RESULTS: We performed lymphatic map in 72 patients, finding the SN in 62 of them (87.3%). The 9 identification failures happened in the first 17 cases. We have not found aberrant drainage routes. A total of 1.164 LN were studied in the 62 patients (18.8 LN/patient), from which 145 are SN (2,34 SN/patient), having found 103 positive LN with the CS and 112 positive with the SS of SN (9+ LN more in 8 patients than detected with the CS). Positivity after CS in the SN group is 17.24% (25/145), while it is 8.53% in the rest (87/1.019) (P < .001). With the CS, 50% of the patients (31/62) were pN+ (4 are N+ exclusively in the SN), and after the SS of the SN, only 1 of the 31 pN0 patients (3.2%) becomes pN1a, with a definitive 51.6% of N+ in the whole series (32 N+ in the 62 patients) (5 are N+ exclusively in the SN). Exclusively with the SS of the SN, FN rate ("-SN, +others", meaning patients who are N+ having -SN) is 54.8% (17/31). With the SS of the SN, 8 of the 62 patients (12.9%) increase their total number of +LN: apart from the patient who turns from pN0 to pN1a, suprastaging from IIA to IIIB (and therefore increasing the total number of pN+ to 32), 5 of the 17 FN in the CS turns into positive (2 change the pN subindex and one is suprastaged from IIIB to IIIC), decreasing FN to 37.5% (12/32 cases). Besides, 2 patients whose SN is already positive in the CS increase the number of +SN after the SS of the SN, therefore both changing their pN subindex and one of them suprastaging from IIIB to IIIC. In summary, 8 patients increase the total number of positive SN after the SS (8/62, 12.9%), 5 of them changing the pN subindex (5/62, 12.9%), even if only 3 of them get suprastaged (3/62, 4.8%), among them the one who turns from pN0 to pN1a. CONCLUSION: Technique is valid and reproducible, with a high detection rate even with a high learning curve. It globally increases the number of affected LN in 12.9% of patients, having prognostic implications in 4.8% (suprastaging rate). Only 3.2% of pN0 patients in the CS turn to be +pN after the SS of the SN, with its therapeutic implications (prescription of adjuvant CT), which could be relevant when extrapolated to a big number of patients. The high FN rate (37.5%) prevents us from accepting the representativeness of SN as the global N status, but it is not clinically relevant in CC, as its aim is not to avoid lymphadenectomy, which remains mandatory (opposite to breast cancer or melanoma in which SN detection decides upon whether to perform or not the lymphadenectomy), but to decide which patients would benefit from adjuvant CT.