After Axillary Lymph Node Dissection Research Articles

Quality of Life After Axillary Lymph Node Dissection Among Racial and Ethnic Minority Women

Higher lymphedema rates after axillary lymph node dissection (ALND) have been found in Black and Hispanic women; however, there is poor correlation between subjective symptoms, quality of life (QOL), and measured lymphedema. Additionally, racial and ethnic differences in QOL have been understudied. To evaluate the association of race and ethnicity with long-term QOL in patients with breast cancer treated with ALND. This cohort study enrolled women aged 18 years and older with breast cancer who underwent unilateral ALND at a tertiary cancer center between November 2016 and March 2020. Preoperatively and at 6-month intervals, arm volume was measured by perometer and QOL was assessed using the Upper Limb Lymphedema-27 (ULL-27) questionnaire, a validated tool for assessing lymphedema that evaluates how arm symptoms affect physical, psychological, and social functioning. Data were analyzed from November 2016 to October 2023. Breast surgery and unilateral ALND in the primary setting or after sentinel lymph node biopsy. Scores in each domain of the ULL-27 were compared by race and ethnicity. Factors impacting QOL were identified using multivariable regression analyses. The study included 281 women (median [IQR] age, 48 [41-58] years) with breast cancer who underwent unilateral ALND and had at least 6 months of follow-up. Of these, 30 patients (11%) self-identified as Asian individuals, 57 (20%) as Black individuals, 23 (8%) as Hispanic individuals, and 162 (58%) as White individuals; 9 individuals (3%) who did not identify as part of a particular group or who were missing race and ethnicity data were categorized as having unknown race and ethnicity. Median (IQR) follow-up was 2.97 (1.96-3.67) years. The overall 2-year lymphedema rate was 20% and was higher among Black (31%) and Hispanic (27%) women compared with Asian (15%) and White (17%) women (P = .04). Subjective arm swelling was more common among Asian (57%), Black (70%), and Hispanic (87%) women than White (44%) women (P < .001), and lower physical QOL scores were reported by racial and ethnic minority women at nearly every follow-up. For example, at 24 months, median QOL scores were 87, 79, and 80 for Asian, Black, and Hispanic women compared with 92 for White women (P = .003). On multivariable analysis, Asian race (β = -5.7; 95% CI, -9.5 to -1.8), Hispanic ethnicity (β = -10.0; 95% CI, -15.0 to -5.2), and having Medicaid (β = -5.4; 95% CI, -9.2 to -1.7) or Medicare insurance (β = -6.9; 95% CI, -10.0 to -3.4) were independently associated with worse physical QOL (all P < .001). Findings of this cohort study suggest that Asian, Black, and Hispanic women experience more subjective arm swelling after unilateral ALND for breast cancer compared with White women. Black and Hispanic women had higher rates of objective lymphedema than their White counterparts. Both minority status and public medical insurance were associated with worse physical QOL. Understanding disparities in QOL after ALND is an unmet need and may enable targeted interventions to improve QOL for these patients.

155. Lymphedema and Autoimmunity: Is There A Link?

BACKGROUND: Despite the emerging evidence highlighting the role of immune responses in driving the progression of breast-cancer-related lymphedema (BCRL), there is a lack of data on the role of autoimmunity in lymphedema development. The purpose of this study was to investigate the association between a wide range of autoimmune diseases and lymphedema development after axillary lymph node dissection (ALND). METHODS: Patients who underwent ALND at our institution between 1995 and 2022 were included. Demographic data, lymphedema development after ALND, and the prevalence of autoimmune disorders were analyzed. RESULTS: 13,071 patients with a mean follow-up time of 88.4±59 months were included. Lymphedema developed in 1047 patients (8%). On univariate analysis, lymphedema development was significantly associated with one or more autoimmune diseases (OR 2.1, 95% CI 1.8-2.5, p<0.0001). The association was strongest for disorders involving the skin (OR 3.1, 95% CI 2.1-4.5, p<0.0001). These findings remained stable in multivariable analyses after adjustment for age, gender, race, BMI, radiation, and chemotherapy history. Preexisting diagnoses of atopic dermatitis (OR 8.5, 95% CI 4.0-17.8, p<0.0001), dermatopolymyositis (OR 4.0, 95% CI 1.2-12.5, p=0.0167), grave’s disease (OR 2.2, 95% CI 1.4-3.4, p=0.0004), vitiligo (OR 2.2, 95% CI 0.9-4.5, p=0.0437) and rheumatoid arthritis (OR 1.73, 95% CI 1.2-2.5, p=0.005) were highly predictive of lymphedema development following ALND. CONCLUSION: This is the first and largest study to date to investigate the association between autoimmune conditions and BCRL development. Our analysis demonstrated significant autoimmune comorbidity of patients with BCRL, suggesting that autoimmune reactions might play a role in the pathophysiology of BCRL development after ALND.

D8. Lymphedema and Autoimmunity: Is There a Link?

PURPOSE: Despite the emerging evidence highlighting the role of immune responses in driving the progression of breast-cancer-related lymphedema (BCRL), there is a lack of data on the role of autoimmunity in lymphedema development. The purpose of this study was to investigate the association between a wide range of autoimmune diseases and lymphedema development after axillary lymph-node dissection (ALND). METHODS: Patients who underwent ALND at our institution between 1995 and 2022 were included. Demographic data, lymphedema development after ALND, and the prevalence of autoimmune disorders were analyzed. RESULTS: 13,071 patients with a mean follow-up time of 88.4±59 months were included. Lymphedema developed in 1047 patients (8%). Lymphedema development was significantly associated with one or more autoimmune diseases (OR 2.1, 95% CI 1.8-2.5, p<0.0001). The association was strongest for disorders involving the skin (OR 3.1, 95% CI 2.1-4.5, p<0.0001). These findings remained stable in multivariable analyses after adjustment for age, gender, ethnicity, BMI, radiation, and chemotherapy history. Preexisting diagnoses of atopic dermatitis (OR 8.5, 95% CI 4.0-17.8, p<0.0001), dermatopolymyositis (OR 4.0, 95% CI 1.2-12.5, p=0.0167), grave’s disease (OR 2.2, 95% CI 1.4-3.4, p=0.0004), vitiligo (OR 2.2, 95% CI 0.9-4.5, p=0.0437) and rheumatoid-arthritis (OR 1.73, 95% CI 1.2-2.5, p=0.005) were highly predictive of lymphedema development following ALND. CONCLUSION: This is the first and largest study to date to investigate the association between autoimmune conditions and BCRL development. Our analysis demonstrated significant autoimmune comorbidity of patients with BCRL, suggesting that autoimmune reactions might play a role in the pathophysiology of BCRL development after ALND.

PC8. Prophylactic Axillary Lymphovenous Bypass Using the Branched Vein Graft Technique

PURPOSE: Prophylactic lymphovenous bypass reduces the risk of lymphedema after axillary lymph node dissection (ALND). Extensive axillary dissection often creates a large gap between disrupted lymphatic vessels and potential recipient veins. The wide distribution of lymphatics throughout the lateral axilla further compounds the difficulty of including all injured vessels for bypass. We describe the technical details and preliminary clinical outcomes of patients who underwent prophylactic lymphovenous bypass using a branched vein graft (BVG) from the superficial circumflex iliac vein (SCIV). METHODS: A retrospective review was performed, focusing on operative details and clinical results. Technique: A 8-10 cm BVG containing valves is harvested from the SCIV and coupled to an appropriate recipient vein. A 27-gauge cannula is used to intubate the BVG lumen at various branch openings as appropriate. This allows a 10-0 suture to be passed outward through the cannula. Lymphatic vessels are then captured and intussuscepted into the BVG with 4 - 6 mm of overlap, without any bunching or kinking. Upon completing the bypass, the intussuscepting suture is removed to avoid lymphatic obstruction. Valves in the graft prevent reflux. RESULTS: Seven patients were identified for inclusion. A median of 3 disrupted lymphatic vessels were encountered per case (range 1-5). Follow-up was 3 weeks to 6 months. Six patients demonstrated no clinical evidence of lymphedema. 1 patient had trace swelling localized to the thumb at 2 months. CONCLUSION: The branched vein graft technique effectively facilitates the immediate bypass of multiple injured lymphatics over a wide area after ALND.

29. Natural History of Breast Cancer-related Lymphedema

PURPOSE: Although breast Cancer-related lymphedema (BCRL) is a chronic disease, the rate of progression is highly variable. The purpose of this prospective longitudinal study was to analyze the natural history of BCRL after axillary lymph node dissection (ALND) and identify predictive variables that may regulate the trajectory of the disease. METHODS: Between 2016 and 2020, we performed baseline arm volume measurements and prospectively followed patients who underwent ALND at a tertiary cancer center every 6 months for 3 years. Demographic data and relative volume change (RVC) were recorded. Patients were divided into four disease trajectories based on RVC (no disease RVC<5%, mild RVC 5-10%, moderate RVC 10-20%, severe RVC>20%) and analyzed using an ordinal logistic regression model. RESULTS: 292 patients with a mean follow-up time of 32.7±6 months were included in the study. Lymphedema (defined as an RVC ≥5%) developed in 39.4% of patients, on average 14.6 months after surgery. Postoperative radiation therapy was the strongest predictor of severe disease trajectory (OR 8.98, 95% CI 1.68-167, p=0.007), followed by African American race (OR 2.16, 95% CI 1.15-4.03, p=0.011), older age (OR 1.03, 95% CI 1.00-1.05 p=0.02) and higher baseline volume differential (OR 0.94, 95% CI 0.89-0.94, p=0.014). Neither chemotherapy nor referral for lymphedema therapy/compression had a significant impact on the disease trajectory. CONCLUSION: This is the largest prospective longitudinal study to identify predictive factors associated with severe BCRL disease trajectory. This information can be used to prioritize aggressive preventative measures such as immediate lymphatic reconstruction or immediate postoperative physical therapy

Plasma Cytokines/Chemokines as Predictive Biomarkers for Lymphedema in Breast Cancer Patients.

Breast cancer-related lymphedema (BCRL) occurs in ~ 40% of patients after axillary lymph node dissection (ALND), radiation therapy (RT), or chemotherapy. First-line palliative treatment utilizes compression garments and specialized massage. Reparative microsurgeries have emerged as a second-line treatment, yet both compression and surgical therapy are most effective at early stages of LE development. Identifying patients at the highest risk for BCRL would allow earlier, more effective treatment. Perometric arm volume measurements, near-infrared fluorescent lymphatic imaging (NIRF-LI) data, and blood were collected between 2016 and 2021 for 40 study subjects undergoing treatment for breast cancer. Plasma samples were evaluated using MILLIPLEX human cytokine/chemokine panels at pre-ALND and at 12 months post-RT. A Mann-Whitney t-test showed that G-CSF, GM-CSF, IFN-2α, IL-10, IL-12p40, IL-15, IL-17A, IL-1β, IL-2, IL-3, IL-6, and MIP-1β were significantly higher at pre-ALND in those presenting with BCRL at 12 months post-RT. MIP-1β and IL-6 were significantly higher at pre-ALND in those who developed dermal backflow, but no BCRL, at 12 months post-RT. Plasma IL-15, IL-3, and MIP-1β were elevated at 12 months after RT in those with clinical BCRL. These findings establish BCRL as a perpetual inflammatory disorder, and suggest the use of plasma cytokine/chemokine levels to predict those at highest risk.

Lymphovenous Bypass and Radiotherapy: A Dosimetric Approach to a Multi-Modality Mystery

<h3>Purpose/Objective(s)</h3> Prophylactic lymphovenous bypass (LVB), in which a severed lymphatic channel is anastomosed to a low-pressure venule, is a microsurgical technique performed after axillary lymph node dissection (ALND) and intended to prevent breast cancer related lymphedema (BCRL). However, the location of these fragile anastomoses in related to radiotherapy (RT) fields remains unstudied. We aimed to identify the typical location of LVB anastomoses and evaluate the feasibility of shielding them from RT dose. <h3>Materials/Methods</h3> Patients underwent LVB with the placement of a circular clip for identification following ALND and received RT at a single institution. Delineation of the target volumes and lymph nodes levels was performed using NRG atlases. Additionally, the axillary and lateral thoracic vessels junction (ALTJ) -previously correlated with BCRL development- was delineated. The LVB clip was contoured and a 0.5cm expansion used to define a LVB volume. RT plans were created with 3D CRT and VMAT. The mean maximum dose to the LVB volume was compared between the two groups using T Test. <h3>Results</h3> Five patients underwent the procedures described above; all underwent mastectomy, ALND and LVB. The LVB anastomoses were identified in axillary Level 1, immediately subjacent (caudal) to the ALTJ. Owing to their location in the tangent fields, the mean maximum dose to LVB volume was 47.2 Gy using 3D planning and 18.7 Gy using VMAT (p<0.0001). <h3>Conclusion</h3> Prophylactic LVB following ALND is increasing in utilization. However, almost all patients undergoing ALND will also receive RT, and effect of RT on the viability of the LVB anastomoses is unknown. In this proof-of-concept study, the location of LVB was consistently identified in level 1 of the axilla. Owing to its location in the tangent fields, exclusion of the LVB volume was typically difficult with 3D CRT. VMAT allowed superior sparing of this structure. Further study is required to clarify the viability of the anastomoses after RT, their dose tolerance, and whether active dose avoidance is necessary.

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

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

Abstract GS4-01: Impact of race and ethnicity on incidence and severity of breast cancer related lymphedema after axillary lymph node dissection: Results of a prospective screening study

Abstract GS4-01: Impact of race and ethnicity on incidence and severity of breast cancer related lymphedema after axillary lymph node dissection: Results of a prospective screening study

Primary Prevention of Cancer-Related Lymphedema Using Preventive Lymphatic Surgery: Systematic Review and Meta-analysis.

Background Several studies have proven prophylactic lymphovenous anastomosis (LVA) performed after lymphadenectomy can potentially reduce the risk of cancer-related lymphedema (CRL) without compromising the oncological treatment. We present a systematic review of the current evidence on the primary prevention of CRL using preventive lymphatic surgery (PLS). Patients and Methods A comprehensive search across PubMed, Cochrane-EBMR, Web of Science, Ovid Medline (R) and in-process, SCOPUS, and ScienceDirect was performed through December 2020. A meta-analysis with a random-effect method was accomplished. Results Twenty-four studies including 1547 patients fulfilled the inclusion criteria. Overall, 830 prophylactic LVA procedures were performed after oncological treatment, of which 61 developed lymphedema. The pooled cumulative rate of upper extremity lymphedema after axillary lymph node dissection (ALND) and PLS was 5.15% (95% CI, 2.9%–7.5%; p < 0.01). The pooled cumulative rate of lower extremity lymphedema after oncological surgical treatment and PLS was 6.66% (95% CI < 1–13.4%, p-value = 0.5). Pooled analysis showed that PLS reduced the incidence of upper and lower limb lymphedema after lymph node dissection by 18.7 per 100 patients treated (risk difference [RD] – 18.7%, 95% CI – 29.5% to – 7.9%; p < 0.001) and by 30.3 per 100 patients treated (RD – 30.3%, 95% CI – 46.5% to – 14%; p < 0.001), respectively, versus no prophylactic lymphatic reconstruction. Conclusions Low-quality studies and a high risk of bias halt the formulating of strong recommendations in favor of PLS, despite preliminary reports theoretically indicating that the inclusion of PLS may significantly decrease the incidence of CRL.

Simultaneous Lymphatic Superficial Circumflex Iliac Artery Perforator Flap Transfer from the Zone 4 Region in Autologous Breast Reconstruction Using the Deep Inferior Epigastric Artery Perforator Flap: A Proof-of-Concept Study.

The incidence of upper extremity lymphedema after breast cancer treatment is reported to be 14% after axillary lymph node dissection (ALND) and 33% after ALND and regional lymph node dissection. The present report describes a novel method in which the afferent lymphatic vessels are harvested with their lymph nodes from the Zone 4 region as a separate flap, the superficial circumflex iliac artery perforator (SCIP) flap, in the setting of autologous breast reconstruction using the deep inferior epigastric artery perforator (DIEP) flap. From September 2017 to September 2020, seven female patients with an average age of 46.9 years (range: 39 to 54 years) underwent autologous breast reconstruction using the DIEP flap and the lymphatic SCIP flap procured separately from the Zone 4 region. All patients had undergone ALND, four patients had undergone radiation therapy, and three patients had established lymphedema at the time of reconstruction. All lymphatic SCIP flaps survived completely. Lymphedema did not occur in any of the four patients to whom the lymphatic flap was transferred for a preventive purpose (average follow-up: 37.5 months). In three patients with established lymphedema at the time of reconstruction, the average rate of estimated volume decrease at the last follow-up (average: 29.0 months) was 12.6%. A lymphatic SCIP flap procured from the Zone 4 region in DIEP flap breast reconstruction can contribute to improvement or prevention of lymphedema with no additional donor site.

Lymphatic Microsurgical Preventive Healing Approach (LYMPHA) for Lymphedema Prevention after Axillary Lymph Node Dissection-A Single Institution Experience and Feasibility of Technique.

While surgical options exist to treat lymphedema after axillary lymph node dissection (ALND), the lymphatic microsurgical preventive healing approach (LYMPHA) has been introduced as a preventive measure performed during the primary surgery, thus avoiding the morbidity associated with lymphedema. Here, we highlight details of our operative technique and review postoperative outcomes. For our patients, limb measurements and body composition analyses were performed pre- and postoperatively. Intraoperatively, axillary reverse lymphatic mapping was performed with indocyanine green (ICG) and lymphazurin. SPY-PHI imaging was used to visualize the ICG uptake into axillary lymphatics. Cut lymphatics from excised nodes were preserved for lymphaticovenous anastomosis (LVA). At the completion of the microanastomosis, ICG was visualized draining from the lymphatic through the recipient vein. A retrospective review identified nineteen patients who underwent complete or partial mastectomy with ALND and subsequent LYMPHA over 19 months. The number of LVAs performed per patient ranged between 1–4 per axilla. The operating time ranged from 32–95 min. There were no surgical complications, and thus far one patient developed mild lymphedema with an average follow up of 10 months. At the clinic follow up, ICG and SPY angiography were used to confirm intact lymphatic conduits with an uptake of ICG across the axilla. This study supports LYMPHA as a feasible and effective method for lymphedema prevention.

Evaluation of apical clips placed during axillary dissection demonstrates potential under‐coverage of axillary radiation therapy target volumes during breast cancer regional nodal irradiation

Evidence-based Australian guidelines (eviQ) recommend adjuvant supraclavicular fossa irradiation after axillary lymph node dissection (ALND) in node-positive breast cancer patients. Disparity between surgically determined versus computed tomography (CT) determined nodal volumes may result in discontiguous nodal volumes and untreated nodal tissue. We examine the extent of untreated nodal tissue in women with breast cancer post-level II or III ALND and adjuvant radiation therapy (RT) using ESTRO contouring guidelines. Female breast cancer patients who underwent level II and III ALND with apical clip placement from 2016 to 2020 and CT simulated in supine position were included. CT-defined axillary level II-IV volumes were contoured using ESTRO guidelines. The distance between the apical clip and RT nodal volumes was measured to indicate extent of untreated tissue. Of 34 eligible patients treated by 7 surgeons, 76% had level II ALND and 24% level III ALND. Only 5.9% of clips entirely encompassed the corresponding RT nodal volumes. 55.9% of clips fell within and 44.1% fell inferolaterally outside the corresponding RT nodal volumes. A median 3.6 cm (range 0-7.5 cm) of undissected nodal tissue would not be included within standard RT target volumes following eviQ recommendations. There is a disparity between surgically determined versus CT determined axillary nodal volumes, leading to discontiguous nodal volumes and untreated axillary nodal tissue, despite following standard radiation contouring guidelines. Intraoperatively placed apical axillary clips may assist radiation oncologists to accurately delineate undissected nodal tissues at risk.

Omitting axillary lymph node dissection after positive sentinel lymph node in the post-Z0011 era: Compliance with NCCN and ASCO clinical guidelines and Z0011 criteria in a large prospective cohort

In the ACOSOG Z0011 trial, patients with primary breast cancer and 1-2 tumor-involved sentinel lymph nodes (SLNs) undergoing breast-conserving surgery had no oncological outcome benefit after axillary lymph node dissection (ALND), despite a relevant rate of non-SLN metastases of 27%. According to the St Gallen expert consensus, and NCCN and ASCO clinical guidelines, ALND may be avoided in patients who meet all ACOSOG Z0011 inclusion criteria. This recommendation can also be extended to patients undergoing mastectomy, with 1 or 2 positive SLNs and an indication for chest wall radiation, in whom axillary radiotherapy can be proposed as an alternative to completion ALND. The aim of this study was to assess non-compliance with the NCCN and ASCO clinical guidelines and Z0011 criteria, namely the rate of performance of completion ALND when it was not recommended, and the rate of failure to perform completion ALND when recommended. Data were prospectively analysed from T1-2 N0 breast cancer patients undergoing an SLN procedure and treated at the Georges-François Leclerc Cancer Center between November 2015 and May 2017. Factors associated with non-compliance treatment decisions were identified using logistic regression. Among 563 patients included, 122 (21.7%) had at least one positive SLN. ALND was not recommended for 76 patients (62.3%), and was recommended in 46 patients (37.7%). The rate of non-compliant treatment was 32% (39/122) overall: ALND was performed despite not being recommended in 16/76 patients (21.1%) and was not performed in 50% of patients in whom it was recommended (23/46). By multivariate analyses, lymphovascular invasion ((Odds Ratio (OR)=6.1; 95% confidence interval (CI): 1.4-26.7; P=0.02)) and only one SLN removed (OR=9.1; 95%CI: 2.2-33.3; P=0.002) were associated with performance of completion ALND when not recommended. Conversely, >1 SLN removed (OR=5.1; 95%CI: 1.2-22.2; P=0.03) was associated with the failure to perform completion ALND when recommended. Almost one third of patients with invasive breast cancer receive treatment that is not in compliance with recommendations regarding completion ALND.

Radiation Oncologists' Approach to Internal Mammary Lymph Node Radiotherapy in Breast Cancer: The Turkish Society for Radiation Oncology Breast Cancer Study Group (TROD 06-005 Survey Study).

BackgroundThis study aimed to examine the practice patterns of radiation oncologists in Turkey regarding radiotherapy to the regional lymph nodes, including internal mammary lymph nodes (IMNs), and identify the factors influencing their clinical decisions in breast cancer patients.MethodsA nationwide, 19-point questionnaire was sent to the physician members of the Turkish Society for Radiation Oncology (TROD).ResultsIn total, 165 radiation oncologists completed the survey, corresponding to a 27% response rate. Regional radiotherapy was used in 64.2% of the patients with 1–3 axillary lymphatic involvement and unfavorable prognostic factors. In contrast, 61.2% of the respondents indicated that IMN should be included in the target volume for regional radiotherapy when the patient had one positive node after axillary lymph node dissection (ALND) in the inner quadrant and central region tumors. However, 71.5% of the respondents chose to include the IMN in the non-inner quadrant and non-central region tumors for patients with four or more positive nodes after ALND. The decision to offer internal mammary lymph node radiotherapy (IMNRT) varied widely and significantly among respondents, years in practice, and the rates of dedicating their clinical time to patients with breast cancer.ConclusionThe results of this survey revealed significant national variation in attitudes regarding the treatment of IMN. Thus, this study may also help document the impact of future studies on clinical practice.

Randomized Study of Wound Drainage on Early Complications After Lymph Node Dissection for Melanoma

IntroductionThe complication rate after axillary lymph node dissection (ALND) and inguinal lymph node dissection (ILND) in melanoma patients is high. The aim of this randomized non-inferiority study was to evaluate the effect of postoperative wound drainage on early complications after ALND and ILND. Materials and methodsBetween 2018 and 2020, 104 stage III melanoma patients operated on with ALND or ILND were randomized to a study group with complete wound drain removal 3 wk after surgery or a control group with progressive drain removal. The primary end point was overall early complications graded according to the modified Clavien-Dindo classification. Secondary endpoints were length of hospital stay and prognostic factors for early complications. ResultsOf the 99 patients analyzed, ALND was performed in 58 patients and ILND in 41 patients. Overall, 62 patients (62.6%) developed early complications: 30 in the study group and 32 in the control group (P = 0.53). The confidence interval for the difference in proportions of patients without early complications in the two groups was −0.27 to 0.11 (P = 0.42), hence non-inferiority could be claimed. Length of hospital stay was 5 d in the study group compared to 6 in the control group (P < 0.01). ILND was associated with increased risk of early complications compared to ALND (75.6% versus 53.4%, P = 0.04). ConclusionsComplete drain removal 3 wk after ALN and ILND in stage III melanoma patients did not increase the risk of early complications compared to progressive drain removal.

Low TGF-β1 in Wound Exudate Predicts Surgical Site Infection After Axillary Lymph Node Dissection

Surgical site infection (SSI) after axillary lymph node dissection (ALND) for breast cancer increases morbidity and delays the onset of adjuvant treatment. Only a few studies have investigated the feasibility of wound exudate analysis in SSI prediction. This study assessed changes in cytokine levels in postsurgical wound exudate after ALND and examined their predictive value for the early diagnosis of SSI. An observational prospective pilot study was conducted in 47 patients with breast cancer undergoing ALND. Wound exudate samples were collected on the first and sixth postoperative days (POD). Interleukin (IL)-1α, IL-1β, IL-4, IL-10, IL-13, tumor necrosis factor alpha (TNF-α), transforming growth factor beta1 (TGF-β1) and vascular endothelial growth factor (VEGF) C and D levels were measured by immunoassay. Patients were followed to detect SSI. SSI was diagnosed in 8/47 (17.0%) patients. Four SSI patients were hospitalized and treated with intravenous antibiotics. The concentration of TGF-β1 in wound exudate was significantly lower on POD#1 in the SSI group compared to the no SSI group (p=0.008). The receiving operator characteristics (ROC) curve for TGF-β1 showed an area under curve of 0.773 (p=0.0149) indicating good diagnostic potential. On POD#6, the concentration of TGF-β1 remained significantly lower (p=0.043) and the concentrations of IL-10 (p=0.000) and IL-1β (0.004) significantly higher in the SSI group compared to the no SSI group. To our knowledge, this is the first study suggesting a predictive role of wound exudate TGF-β1 levels for SSI. Our results suggest that the risk for SSI can be detected already on POD#1 and that the assessment of TGF-β1 levels in the wound exudate after ALND can provide a usefull method for the early detection of SSI. The key findings of this pilot study warrant verification in a larger patient population.

Economic implications of ACOSOG Z0011 trial application into clinical practice at the European Institute of Oncology

Background and objectivesThe American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated that in clinically node-negative women undergoing breast-conserving therapy (BCT) and found to have metastases to 1 or 2 sentinel nodes, sentinel lymph node biopsy (SLNB) alone resulted in rates of local control, disease-free survival, and overall survival equivalent to those seen after axillary lymph node dissection (ALND), but with significantly lower morbidity. Application of the Z0011 guidelines resulted in fewer ALNDs without affecting locoregional recurrence or survival. Changes in practice inevitably affect health care costs. The current study investigated the actual impact of applying the Z0011 guidelines to eligible patients and determined the costs of care at a single institution. Patients and methodsWe compared axillary nodal management and cost data in breast cancer patients who met the Z0011 criteria and were treated with BCT and SLNB. Patients were allocated into two mutually exclusive cohorts based on the date of surgery: pre-Z0011 (June 2013 to December 2015) and post-Z0011 (June 2016 to December 2018). ResultsOf 3912 patients, 433 (23%) and 357 (17.6%) patients in the pre- and post-Z0011 era had positive lymph nodes. ALND decreased from 15.3% to 1.57% in the post-Z0011 era. The mean overall cost of SLNB in the pre-Z0011 cohort was €1312 per patient, while that for SLNB with completion ALND was €2613. Intraoperative frozen section (FS) use decreased from 100% to 12%. Omitting the FS decreased mean costs from €247 to €176. The mean total cost in the pre-Z0011 cohort was €1807 per patient, while in the post-Z0011 cohort it was €1498. The application of Z0011 resulted in an overall mean cost savings of €309 for each patient. ConclusionsApplication of the Z0011 criteria to patients undergoing BCT at our institution results in more than half a million Euro cost savings.

Effect of Poloxamer-Based Thermo-Sensitive Sol-Gel Agent on Upper Limb Dysfunction after Axillary Lymph Node Dissection: A Double-Blind Randomized Clinical Trial.

PurposeRestricted shoulder motion is a major morbidity associated with a lower quality of life and disability after axillary lymph node dissection (ALND) in patients with breast cancer. This study sought to evaluate the antiadhesive effect of a poloxamer-based thermosensitive sol-gel (PTAS) agent after ALND.MethodsWe designed a double-blind, multicenter randomized controlled study to evaluate the clinical efficacy and safety of PTAS in reducing upper-limb dysfunction after ALND. The primary outcome was the change in the range of motion (ROM) of the shoulder before surgery and 4 weeks after ALND (early postoperative period). Secondary outcomes were shoulder ROM at six months, axillary web syndrome, and lymphedema (late postoperative period).ResultsA total of 170 patients with planned ALND were randomly assigned to one of 2 groups (poloxamer and control) and 15 patients were excluded. In the poloxamer group (n = 76), PTAS was applied to the surface of the operative field after ALND. ALND was performed without the use of poloxamer in the control group (n = 79). Relative to the control group, the poloxamer group had significantly lower early postoperative restrictions in total shoulder ROM at four weeks (−30.04 ± 27.76 vs. −42.59 ± 36.79; p = 0.0236). In particular, the poloxamer group showed greater reductions in horizontal abduction at four weeks (−3.92 ± 9.80 vs. −10.25 ± 15.42; p = 0.0050). The ROM of the shoulder at 24 weeks, axillary web syndrome, and lymphedema were not significantly different between the two groups. No adverse effects were observed in either group.ConclusionWe suggest that poloxamer might improve the early postoperative shoulder ROM in patients with breast cancer who have undergone ALND.Trial RegistrationClinicalTrials.gov Identifier: NCT02967146

Guiding Measurement Protocols of Connected Medical Devices Using Digital Twins: A Statistical Methodology Applied to Detecting and Monitoring Lymphedema

This article describes the preparation of a clinical study on a connected medical device dedicated to facilitate the prevention of lymphedema for patients treated for breast cancer after axillary lymph node dissection (ALND), and to alert them of any manifestation or resurgence in order to prevent its aggravation. A simulator of the entire physical process called digital twin has been developed for this purpose, in a <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">hardware-in-the-loop</i> framework. Statistical calibration of its input parameters, by stochastic inversion and using sensitivity studies, led to establish one or more measurement protocols allowing to capture the signal on a mobile device (phone or tablet) and to detect signal breaks that are physically significant. The measured signal makes it possible to report quickly on the worsening of the patient’s condition and to warn the therapists within a very reasonable period of time. The general methodology of this work seems to us to be easily reproducible in the preparation of clinical studies of other types for connected devices, which aim to develop measurement protocols limiting the often significant cost of such studies. One of the immediate prospects of this work is the initiation of a clinical study on different patients who have been treated by surgery for breast cancer, after improving the robustness of the design of the prototype to take into account the uncertainties affecting the measurements.