Current axillary management of patients with early breast cancer and low-volume nodal disease undergoing primary surgery: results of a United Kingdom national practice survey.

PURPOSE: UK NICE guidelines recommend axillary node clearance (ANC) should be performed in all patients with biopsy-proven node-positive breast cancer having primary surgery. There is, however, increasing evidence such extensive surgery may not always be necessary. Targeted axillary dissection (TAD) may be an effective alternative in patients with low-volume nodal disease who are clinically node negative (cN0) but have abnormal nodes detected radiologically. This survey aimed to explore current management of this group to inform feasibility of a future trial. METHODS: An online survey was developed to explore current UK management of patients with low-volume axillary disease and attitudes to a future trial. The survey was distributed via breast surgery professional associations and social media from September to November 2022. One survey was completed per unit and simple descriptive statistics used to summarise the results. RESULTS: 51 UK breast units completed the survey of whom 78.5% (n = 40) reported performing ANC for all patients with biopsy-proven axillary nodal disease having primary surgery. Only 15.7% of units currently performed TAD either routinely (n = 6, 11.8%) or selectively (n = 2, 3.9%). There was significant uncertainty (83.7%, n = 36/43) about the optimal surgical management of these patients. Two-thirds (n = 27/42) of units felt an RCT comparing TAD and ANC would be feasible. CONCLUSIONS: ANC remains standard of care for patients with low-volume node-positive breast cancer having primary surgery in the UK, but considerable uncertainty exists regarding optimal management of this group. This survey suggests an RCT comparing the outcomes of TAD and ANC may be feasible.

Preoperative Prediction of Lymph Node Metastases in Nonfunctional Pancreatic Neuroendocrine Tumors Using a Combined CT Radiomics-Clinical Model.

BACKGROUND: PanNETs are a rare group of pancreatic tumors that display heterogeneous histopathological and clinical behavior. Nodal disease has been established as one of the strongest predictors of patient outcomes in PanNETs. Lack of accurate preoperative assessment of nodal disease is a major limitation in the management of these patients, in particular those with small (< 2 cm) low-grade tumors. The aim of the study was to evaluate the ability of radiomic features (RF) to preoperatively predict the presence of nodal disease in pancreatic neuroendocrine tumors (PanNETs). PATIENTS AND METHODS: An institutional database was used to identify patients with nonfunctional PanNETs undergoing resection. Pancreas protocol computed tomography was obtained, manually segmented, and RF were extracted. These were analyzed using the minimum redundancy maximum relevance analysis for hierarchical feature selection. Youden index was used to identify the optimal cutoff for predicting nodal disease. A random forest prediction model was trained using RF and clinicopathological characteristics and validated internally. RESULTS: Of the 320 patients included in the study, 92 (28.8%) had nodal disease based on histopathological assessment of the surgical specimen. A radiomic signature based on ten selected RF was developed. Clinicopathological characteristics predictive of nodal disease included tumor grade and size. Upon internal validation the combined radiomics and clinical feature model demonstrated adequate performance (AUC 0.80) in identifying nodal disease. The model accurately identified nodal disease in 85% of patients with small tumors (< 2 cm). CONCLUSIONS: Non-invasive preoperative assessment of nodal disease using RF and clinicopathological characteristics is feasible.

Advances and residual knowledge gaps in the neck management of head and neck squamous cell carcinoma patients with advanced nodal disease undergoing definitive (chemo)radiotherapy for their primary.

PURPOSE: Substantial changes have been made in the neck management of patients with head and neck squamous cell carcinomas (HNSCC) in the past century. These have been fostered by changes in cancer epidemiology and technological progress in imaging, surgery, or radiotherapy, as well as disruptive concepts in oncology. We aimed to review changes in nodal management, with a focus on HNSCC patients with nodal involvement (cN+) undergoing (chemo)radiotherapy. METHODS: A narrative review was conducted to review current advances and address knowledge gaps in the multidisciplinary management of the cN+ neck in the context of (chemo)radiotherapy. RESULTS: Metastatic neck nodes are associated with poorer prognosis and poorer response to radiotherapy, and have therefore been systematically treated by surgery. Radical neck dissection (ND) has gradually evolved toward more personalized and less morbid approaches, i.e., from functional to selective ND. Omission of ND has been made feasible by use of positron-emission tomography/computed tomography to monitor the radiation response in cN+ patients. Human papillomavirus-driven oropharyngeal cancers and their cystic nodes have shown dramatically better prognosis than tobacco-related cancers, justifying a specific prognostic classification (AJCC) creation. Finally, considering the role of lymph nodes in anti-tumor immunity, de-escalation of ND and prophylactic nodal irradiation in combination are intense areas of investigation. However, the management of bulky cN3 disease remains an issue, as aggressive multidisciplinary strategies or innovative combined treatments have not yet significantly improved their prognosis. CONCLUSION: Personalized neck management is an increasingly important aspect of the overall therapeutic strategies in cN+ HNSCC.

Targeted axillary dissection reduces residual nodal disease in clinically node- positive breast cancer after neoadjuvant chemotherapy.

BACKGROUND: Any advantage of performing targeted axillary dissection (TAD) compared to sentinel lymph node (SLN) biopsy (SLNB) is under debate in clinically node-positive (cN+) patients diagnosed with breast cancer. Our objective was to assess the feasibility of the removal of the clipped node (RCN) with TAD or without imaging-guided localisation by SLNB to reduce the residual axillary disease in completion axillary lymph node dissection (cALND) in cN+ breast cancer. METHODS: A combined analysis of two prospective cohorts, including 253 patients who underwent SLNB with/without TAD and with/without ALND following NAC, was performed. Finally, 222 patients (cT1-3N1/ycN0M0) with a clipped lymph node that was radiologically visible were analyzed. RESULTS: Overall, the clipped node was successfully identified in 246 patients (97.2%) by imaging. Of 222 patients, the clipped lymph nodes were non-SLNs in 44 patients (19.8%). Of patients in cohort B (n=129) with TAD, the clipped node was successfully removed by preoperative image-guided localisation, or the clipped lymph node was removed as the SLN as detected on preoperative SPECT-CT. Among patients with ypSLN(+) (n=109), no significant difference was found in non-SLN positivity at cALND between patients with TAD and RCN (41.7% vs. 46.9%, p=0.581). In the subgroup with TAD with axillary lymph node dissection (ALND; n=60), however, patients with a lymph node (LN) ratio (LNR) less than 50% and one metastatic LN in the TAD specimen were found to have significantly decreased non-SLN positivity compared to others (27.6% vs. 54.8%, p=0.032, and 22.2% vs. 50%, p=0.046). CONCLUSIONS: TAD by imaging-guided localisation is feasible with excellent identification rates of the clipped node. This approach has also been found to reduce the additional non-SLN positivity rate to encourage omitting ALND in patients with a low metastatic burden undergoing TAD.

Rates of pathologic nodal disease among cN0 and cN1 patients undergoing routine axillary ultrasound and neoadjuvant chemotherapy.

PURPOSE: Routine axillary ultrasound (AxUS) in patients receiving neoadjuvant chemotherapy (NAC) remains controversial. Here, we report rates of AxUS-detected nodal disease among patients with normal clinical exams, and rates of pathologic nodal disease after NAC based on method of nodal disease detection. METHODS: Clinicopathologic findings were prospectively collected for stage I-III breast cancer patients selected for NAC. All patients had pre-treatment AxUS, suspicious nodes were biopsied. The following four patient cohorts were examined: patients with suspicious exam or AxUS but negative biopsy (Suspicious cN0); those with normal exam and normal AxUS (Not Suspicious cN0); those with normal exam but suspicious AxUS and positive biopsy (AxUS-detected cN1); and those with abnormal exam and positive biopsy (exam-detected cN1). Sentinel (SLN) and non-sentinel lymph nodes (non-SLN) were evaluated by immunohistochemistry; nodal metastases of any size were considered positive. RESULTS: 500 patients were included. Of 310 patients with normal axillary exams, 160 had suspicious AxUS, 65 were biopsy-negative (Suspicious cN0) and 95/310 (30.6%) were biopsy-positive (AxUS-detected cN1). Of 190 with abnormal axillary exams, 166 were biopsy-proven node-positive (exam-detected cN1) and 24 were AxUS or biopsy-negative (Suspicious cN0). Rates of pathologic nodal disease were 20/150 (13.3%) among Not Suspicious cN0 patients, 12/89 (13.5%) among Suspicious cN0 (p = 0.97). Rates of residual nodal disease were 55/95 (57.9%) among AxUS-detected cN1 patients, 102/166 (61.4%) among exam-detected cN1 (p = 0.57). CONCLUSION: AxUS detected nodal disease in 30.6% of patients with normal clinical exams selected for NAC. Rates of pathologic nodal disease were similar among AxUS-detected and exam-detected cN1 patients.

Axillary response rates to neoadjuvant chemotherapy in breast cancer patients with advanced nodal disease.

PURPOSE: Utilization of sentinel lymph node biopsy (SLNB) in breast cancer patients with positive nodes after neoadjuvant chemotherapy (NAC) has increased. We examine axillary response rates after NAC in patients with clinical N2-3 disease to determine whether SLNB should be considered. METHODS: Breast cancer patients with clinical N2-3 (AJCC 7th Edition) disease who received NAC followed by surgery were selected from our institutional tumor registry (2009-2018). Axillary response rates were assessed. RESULTS: Ninety-nine patients with 100 breast cancers were identified: 59 N2 (59.0%) and 41 (41.0%) N3 disease; 82 (82.0%) treated with axillary lymph node dissection (ALND) and 18 (18.0%) SLNB. The majority (99.0%) received multiagent NAC. In patients undergoing ALND, cCR was observed in 20/82 patients (24.4%), pathologic complete response (pCR) in 15 patients (18.3%), and axillary pCR in 17 patients (20.7%). In patients with a cCR, pCR was identified in 60.0% and was most common in HER2+ patients (34.6%). CONCLUSION: In this analysis of patients with clinical N2-3 disease receiving NAC, 79.3% of patients had residual nodal disease at surgery. However, 60.0% of patients with a cCR also had a pCR. This provides the foundation to consider evaluating SLNB and less extensive axillary surgery in this select group.

Lymphopenia and clinical outcomes in patients with residual nodal disease after neoadjuvant chemotherapy for breast cancer.

BACKGROUND: Patients with residual nodal disease after neoadjuvant chemotherapy for breast cancer have a poor prognosis. We wanted to evaluate whether lymphopenia after treatment for breast cancer impacted clinical outcomes. MATERIALS AND METHODS: We assessed 99 patients with node-positive disease after neoadjuvant chemotherapy. Absolute lymphocyte count was recorded 1 year after radiation. Dates of local, regional, and distant failure were recorded. Time to event outcomes were evaluated using Kaplan-Meier analysis. Multivariable analysis determined factors predictive for overall survival. RESULTS: Median follow-up was 44 months (range 3-150). Median age was 48 years (range 23-79). Twenty-six patients (26%) had lymphopenia 1 year after RT. Patients with lymphopenia had a greater incidence of regional (p = 0.03) and distant failure (p = 0.009) compared to those with normal lymphocyte counts and had a 6.05 greater risk of death (p = 0.0002). CONCLUSIONS: In patients with residual nodal disease after neoadjuvant chemotherapy, lymphopenia after breast cancer treatment was associated with overall survival. The relationship between lymphopenia and breast cancer outcomes warrants further investigation.

Smoking, age, nodal disease, T stage, p16 status, and risk of distant metastases in patients with squamous cell cancer of the oropharynx.

BACKGROUND: With an expectation of excellent locoregional control, ongoing efforts to de-intensify therapy for patients with human papillomavirus-associated squamous cell oropharyngeal cancer necessitate a better understanding of the metastatic risk for patients with this disease. The objective of this study was to determine what factors affect the risk of metastases in patients with squamous cell cancers of the oropharynx. METHODS: Under a shared use agreement, 547 patients from Radiation Therapy Oncology Group 0129 and 0522 with nonmetastatic oropharyngeal squamous cell cancers who had a known p16 status and smoking status were analyzed to assess the association of clinical features with the development of distant metastases. The analyzed factors included the p16 status, sex, T stage, N stage, age, and smoking history. RESULTS: A multivariate analysis of 547 patients with a median follow-up of 4.8 years revealed that an age ≥ 50 years (hazard ratio [HR], 3.28; P = .003), smoking for more than 0 pack-years (HR, 3.09; P < .001), N3 disease (HR, 2.64; P < .001), T4 disease (HR, 1.63; P = .030), and a negative p16 status (HR, 1.60; P = .044) were all factors associated with an increased risk of distant disease. CONCLUSIONS: Age, smoking, N3 disease, T4 disease, and a negative p16 status were associated with the development of distant metastases in patients with squamous cell cancers of the oropharynx treated definitively with concurrent chemoradiation.

Evolution in practice patterns of axillary management following mastectomy in patients with 1-2 positive sentinel nodes.

PURPOSE: The optimal management of breast cancer patients with a positive sentinel lymph node (SLN) who undergo mastectomy remains controversial. This study aimed to describe treatment patterns of patients with positive SLNs who undergo mastectomy using a large population-based database. METHODS: The NCDB was queried for cT1-2N0 breast cancer patients treated with mastectomy between 2006 and 2014 who had 1-2 positive SLNs. Patients receiving neoadjuvant chemotherapy were excluded. Axillary management included SLN dissection (SLND) alone, axillary lymph node dissection (ALND), post-mastectomy radiation (PMRT) alone, and ALND + PMRT. Trends of axillary management and patient characteristics were examined. RESULTS: Among 12,190 patients who met study criteria, the use of ALND dropped with a corresponding increase in other approaches. In 2006, 34% of patients had SLND alone, 47% ALND, 8% PMRT and 11% ALND + PMRT. By 2014, 37% had SLND, 23% ALND, 27% PMRT and 13% ALND + PMRT. Patients who underwent SLND alone were older (mean 60.6 years) with more comorbidities (Charlson-Deyo score > 2), smaller primary tumors (mean 2.1 cm), well-differentiated histology, hormone receptor-positive, HER2-negative tumors, without lymphovascular invasion (all P values < 0.01). Treatment with SLND alone was more likely if patients had only one positive SLN (P < 0.001) or micrometastatic disease (P < 0.001), and were treated at community centers compared with academic centers (P < 0.001). CONCLUSIONS: The management of breast cancer patients undergoing mastectomy with positive SLNs has evolved over time with decreased use of ALND and increased use of radiation. Some patient subsets are underrepresented in recent clinical trials, and therefore, future trials should focus on these patients.

The risk of nodal disease in patients with pathological complete responses after neoadjuvant chemoradiation for rectal cancer: a systematic review, meta-analysis, and meta-regression.

BACKGROUND: This systematic review and meta-analysis seek to evaluate the prevalence of nodal disease in rectal cancer patients with pathological complete responses (pCR) after neoadjuvant chemoradiotherapy (ypT0N+). METHODS: This study conformed to the PRISMA guidelines. A search was performed on major databases to identify relevant articles. Meta-analyses of pooled proportions were performed on rectal cancer with pCR and ypT0N+. Meta-regression was undertaken to identify sources of heterogeneity, and the Newcastle-Ottawa Scale (NOS) was employed to assess the risk of bias. RESULTS: A total of 18 studies were included, totaling 7568 patients. The overall risk of bias was low, since all studies scored 6 and above out of 9 on the NOS. Preoperatively, the pooled proportions of patients with T3/T4 tumors and clinically positive nodal disease were 84.08% (95% CI 74.19 to 91.99%) and 52.14% (95% CI 35.02 to 69.00%) respectively. The prevalence of pCR in the whole pool was 18.52% (95% CI 13.31 to 24.35%; I2 = 93.85%; P = 0.00), and meta-regression showed a significantly negative relationship with patient age (ß = - 0.03, 95% CI - 0.03 to - 0.02; P = 0.00). The pooled prevalence of ypT0N+ was 4.61% (95% CI 2.41 to 7.28%; I2 = 52.27%; P = 0.01), and meta-regression demonstrated a significantly positive relationship with male gender (ß = 1.06, 95% CI 1.00 to 1.12; P = 0.04). CONCLUSION: There is a small risk of ypN+ in patients with pCR after neoadjuvant CRT and surgery for rectal cancer. However, further research is warranted to establish these findings and to identify predictive factors for this specific group of patients.

Long-term oncological outcomes in patients with limited nodal disease undergoing radical prostatectomy and pelvic lymph node dissection without adjuvant treatment.

PURPOSE: This study aimed at analysing long-term oncologic outcomes in prostate cancer patients with limited nodal disease (1-2 positive lymph nodes) without adjuvant therapy after radical prostatectomy (RP). METHODS: We retrospectively analysed data of 209 pN1 patients who underwent RP between January 1998 and 2010 with one (160) or two (49) histologically proven positive lymph nodes (LNs) without adjuvant treatment. Biochemical recurrence-free survival, metastasis-free survival and cancer-specific survival (CSS) were reported. In multivariable regression analyses further prognosticators of oncologic outcome in these patients were analysed. RESULTS: Median follow-up was 60.2 months. There was no significant difference in oncologic outcome between patients with one and two positive LNs. 73.1% (76.7%) of patients with one (two) positive LNs had biochemical recurrence during the follow-up period, 20.0% (25.6%) developed metastasis and 8.1% (6.1%) died of their disease. The only factors significantly associated with oncologic outcome in multivariable analysis were Gleason score and pT-stage. CONCLUSIONS: Patients with limited nodal disease (1-2 positive LNs) without adjuvant therapy showed favourable CSS-rates above 94% after 5 years. A subgroup of these patients (37%) remained metastasis-free without need of salvage treatment.

Cardiac resynchronisation therapy in patients with atrioventricular nodal disease and reduced ejection fraction - can we afford it?

BACKGROUND: Recent pacing guidelines from the European Society of Cardiology recommend cardiac resynchronisation therapy (CRT) in patients with an atrioventricular (AV) nodal pacing indication and reduced ejection fraction (EF). However, concerns over added expenditure may limit its widespread implementation. We investigate the potential incremental cost of biventricular over right ventricular pacing if such a practice was adopted. METHODS: Retrospective analysis was performed of devices implanted over eight years. The database was analysed for device type, pacing indication and EF. Cost analysis was performed. RESULTS: 1751 devices were implanted over eight years at an averaged cost of AUD$1,369,125 per year. 172 with CRT were excluded. 25.4 (11.6%) patients per year had an EF≤50% and AV nodal disease. 18.4 were in sinus rhythm (SR) and 7.0 in atrial fibrillation (AF). Of these, 13.5 (6.2%) had EF≤45% (9.9 SR, 3.6 AF) and 8.2 (3.8%) had EF≤35% (5.6 SR, 2.6 AF). Based on an incremental cost of $4,000 per device, if all patients with EF≤50% received CRT, the total cost increment per year equates to $73,500 for SR patients or $101,500 if AF patients were included. In patients with EF≤35% and EF≤45%, this amounts to $22,500 and $39,500 per year for SR patients respectively or $33,000 and $54,000 per year if AF patients were included. Depending on the EF and rhythm, this represents a 1.6% to 7.4% increase per year in the pacing budget for an increased patient population of between 2.6% (EF≤35% in SR) to 11.6% (EF≤50%). CONCLUSION: A small proportion of additional patients will qualify for CRT based on the chosen cut-off and rhythm. Although the individual incremental cost for biventricular over right ventricular pacing is high in patients with AV nodal disease and reduced EF, overall this represents at most, a modest increase in the total pacing budget.

High-grade endometrial cancer: revisiting the impact of tumor size and location on outcomes.

OBJECTIVE: Research on tumor size (TS) and intracavitary tumor location in endometrial cancer has focused primarily on low-grade tumors. Data in patients with high-grade histology are limited. Our goal is to determine if TS or lower uterine segment (LUS) involvement, is associated with nodal disease and recurrence in women with high-grade endometrial cancer. METHODS: This is an IRB-approved, multi-institutional cohort study of patients with clinically early-stage, high-grade endometrial cancer who underwent comprehensive surgical staging. Records were reviewed for demographic, pathologic, and treatment data. Nodal involvement and recurrence as a function of TS and location were estimated with odds ratios and hazard ratios. RESULTS: From 2005 to 2012, 208 patients were identified. Of these, 188 patients had tumor location and 183 had TS reported. There were 75 endometrioid (36.1%), 35 serous (16.8%), 12 clear cell (5.8%), and 26 carcinosarcoma (12.5%) cases, and 60 (28.8%) undifferentiated or mixed histologies. There were 55 recurrences (median follow up 17.2 mo). LUS tumors were associated with pelvic and para-aortic nodal disease (OR 3.83, 95% CI 1.70-8.60, p<0.01, OR 5.13, 95% CI 1.96-13.45, p<0.01). TS ≥ 2 cm was associated with pelvic nodal disease (27.4% vs. 0%, p=0.01; OR 10.00, p=0.01). Neither TS nor LUS location was independently associated with recurrence. CONCLUSIONS: In high-grade endometrial cancers, tumor involvement of the LUS and TS>2 cm was associated with pelvic nodal disease, and LUS involvement was also significantly associated with para-aortic nodal disease. There was no association between LUS involvement or TS>2 cm and recurrence.

Pathological Features Associated with Lymph Node Disease in Patients with Appendiceal Neuroendocrine Tumors.

This study aimed to evaluate the role of pathological features beyond tumor size in the risk of lymph node metastasis in appendiceal neuroendocrine tumors. Analyzing data from the national cancer database, we found that among 5353 cases, 18.8% had lymph node metastasis. Focusing on tumors smaller than 2 cm, a subject of considerable debate in treatment strategies, we identified lymphovascular invasion as one of the strongest predictors of lymph node disease. Interestingly, extension into the subserosa and beyond, a current factor in the staging system, was not a strong predictor. These findings suggest that careful interpretation of pathological features is needed when selecting therapeutic approaches using current staging systems.

Pattern of recurrence after stereotactic body radiotherapy of nodal lesions: a single-institution analysis.

OBJECTIVES: Stereotactic body radiotherapy (SBRT) and/or single fraction stereotactic body radiosurgery (SRS) are effective treatment options for the treatment of oligometastatic disease of lymph nodes. Despite the encouraging local control rate, progression-free survival remains unfair due to relapses that might occur in the same district or at other sites. The recurrence pattern analysis after nodal local ablative RT (laRT) in oligometastatic patients is presented in this study. METHODS: The pattern of failure of patients with nodal metastases who were recruited and treated with SBRT in the Destroy-1 or SRS in the Destroy-2 trials was investigated in this single-institution, retrospective analysis. The different relapsed sites following laRT were recorded. RESULTS: Data on 190 patients who received SBRT or SRS on 269 nodal lesions were reviewed. A relapse rate of 57.2% (154 out of 269 nodal lesions) was registered. The pattern of failure was distant in 88 (57.4%) and loco-regional in 66 (42.6%) patients, respectively. The most frequent primary malignancies among patients experiencing loco-regional failure were genitourinary and gynaecological cancers. Furthermore, the predominant site of loco-regional relapse (62%) was the pelvic area. Only 26% of locoregional relapses occurred contra laterally, with 74% occurring ipsilaterally. CONCLUSIONS: The recurrence rates after laRT for nodal disease were more frequent in distant regions compared to locoregional sites. The most common scenarios for locoregional relapse appear to be genitourinary cancer and the pelvic site. In addition, recurrences often occur in the same nodal station or in a nodal station contiguous to the irradiated nodal site. ADVANCES IN KNOWLEDGE: Local ablative radiotherapy is an effective treatment in managing nodal oligometastasis. Despite the high local control rate, the progression free survival remains dismal with recurrences that can occur both loco-regionally or at distance. To understand the pattern of failure could aid the physicians to choose the best treatment strategy. This is the first study that reports the recurrence pattern of a significant number of nodal lesions treated with laRT.

Elective Neck Dissection in Patients Undergoing Salvage Laryngectomy: Outcomes, Complications, and Considerations.

Objective In this study, we sought to identify the predictors for occult nodal disease (OND) and compare oncologic outcomes in patients undergoing elective neck dissection (END) at the time of salvage laryngectomy (SLE) versus the observation group. Methods A retrospective chart review was conducted involving all patients with clinically node-negative (cN0) necks who underwent SLE at a tertiary academic center over 12 years. A total of 58 patients met the inclusion criteria and were divided into two groups: END (n=39) and observation (n=19). Primary endpoints were OND, regional recurrence-free survival (RRFS), and disease-specific survival (DSS). Univariate analysis was performed to establish the association between variables with Fisher's exact test and Mann-Whitney U test. Survival analysis was performed with the log-rank test. Results The cohort comprised 46 (79.3%) males and 12 (20.7%) females, with a mean age of 60 years. Pathological nodal disease was identified in five of 71 (7%) examined neck dissection specimens, with positive nodes found in levels II through IV. The only statistically significant predictor of OND was the rT3/rT4 stage (p=0.017). There were no differences in perioperative complications, RRFS (p=0.216), or DSS (p=0.298) between the END and observation groups. Conclusions In cN0 necks, the advanced recurrent T-stage (rT3-rT4) is a predictor for OND. As OND was found involving levels II, III, and IV in this study's specimens, formal lateral neck dissection should be the procedure of choice if END is to be performed alongside SLE. While END did not show a significantly higher morbidity profile versus conservative management in this cohort, the procedure did not improve loco-regional control or survival, even when stratifying by tumor stage.

Head and Neck Merkel Cell Carcinoma: Therapeutic Benefit of Adjuvant Radiotherapy for Nodal Disease.

OBJECTIVES: To evaluate the therapeutic effect of post-operative radiotherapy (PORT) with respect to nodal status among patients with head and neck Merkel cell carcinoma (HNMCC). METHODS: In this retrospective study, we queried Surveillance, Epidemiology, and End Results (SEER) dataset from 2000 through 2019. We included all adult patients who received primary surgical resection for histologically confirmed treatment naive HNMCC. Entropy balancing was used to reweight observations such that there was covariate balance between patients who received PORT and patients who received surgical resection alone. Doubly robust estimation was achieved by incorporating weights into a multivariable cox proportional hazards model. Planned post hoc subgroup analysis was performed to evaluate the impact of PORT by pathological node status. RESULTS: Among 752 patients (mean age, 73.3 years [SD 10.8]; 64.2% male; 91.2% White; 41.9% node-positive), 60.4% received PORT. Among node-positive patients, we found that PORT was associated with improved overall survival (OS) (aHR, 0.55; 95% CI, 0.37-0.81; p = 0.003) and improved disease-specific survival (DSS) (aHR, 0.57; 95% CI, 0.35-0.92; p = 0.022). Among node-negative patients, we found that PORT was not associated with OS and was associated with worse DSS (aHR, 2.34; 95% CI, 1.30-4.23; p = 0.005). CONCLUSIONS: We found that PORT was associated with improved OS and DSS for node-positive patients and worse DSS for node-negative patients. For HNMCC treated with primary surgical resection, these data confirm the value of PORT for pathologically node-positive patients and support the use of single modality surgical therapy for pathologically node-negative patients without other adverse risk factors. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3587-3594, 2024.

Analysis of predictive factors of unforeseen nodal metastases in resected clinical stage I NSCLC.

Background: Despite notable advances made in preoperative staging, unexpected nodal metastases after surgery are still significantly detected. In this study we aim to analyze the upstaging rate in patients with clinical stage I NSCLC without evidence of nodal disease in the preoperative staging who underwent lobectomy and radical lymphadenectomy. Methods: Patients who underwent lobectomy and systematic lymphadenectomy for clinical stage I NSCLC were evaluated. Exclusion criteria included the neoadjuvant treatment, incomplete resection and no adherence to preoperative guidelines. Results: A total of 297 patients were included in the study. 159 patients were female, and the median age was 68 (61 - 73). The variables that showed a significant correlation with the upstaging rate at the univariate analysis were the number of resected lymph nodes and micropapillar/solid adenocar-cinoma subtype. This result was confirmed in the multivariate analysis with a OR= 2.545 (95%CI 1.136-5.701; p=0.02) for the number of resected lymph nodes and a OR=2.717 (95%CI 1.256-5.875; p=0.01) for the high-grade pattern of adenocarcinoma. Conclusion: Our results showed that in a homogeneous cohort of patients with clinical stage I NSCLC, the number of resected lymph nodes and the histological subtype of adenocarcinoma can significantly be associated with nodal metastasis.

ALK rearrangement is an independent predictive factor of unexpected nodal metastasis after surgery in early stage, clinical node negative lung adenocarcinoma.

OBJECTIVES: Despite notable advances made in preoperative staging, unexpected nodal metastases after surgery are still significantly detected. Given the promising role of neoadjuvant targeted treatments, the definition of novel predictive factors of nodal metastases is an extremely important issue. In this study we aim to analyze the upstaging rate in patients with early stage NSCLC without evidence of nodal disease in the preoperative staging who underwent lobectomy and radical lymphadenectomy. MATERIAL AND METHODS: Patients who underwent lobectomy and systematic lymphadenectomy for early stage LUAD without evidence of nodal disease at the preoperative staging using NGS analysis for actionable molecular targets evaluation after surgery were evaluated. Exclusion criteria included the neoadjuvant treatment, incomplete resection and no adherence to preoperative guidelines. RESULTS: A total of 359 patients were included in the study. 172 patients were female, and the median age was 68 (61-72). The variables that showed a significant correlation with the upstaging rate at the univariate analysis were the ALK rearrangement, the number of resected lymph nodes and the diameter of the tumor. This result was confirmed in the multivariate analysis, with an OR of 8.052 (CI95% 3.123-20.763, p = 0.00001) for ALK rearrangement, 1.087 (CI95% 1.048-1.127, p = 0.00001) for the number of resected nodes and 1.817 (CI95% 1.214-2.719, p = 0.004) for cT status. CONCLUSION: Our results showed that in a homogeneous cohort of patients with clinical node early stage LUAD the ALK rearrangement, the number of resected lymph nodes and the tumor diameter can significantly predict nodal metastasis.

Abbreviated MRI for Comprehensive Regional Lymph Node Staging during Pre-Operative Breast MRI.

BACKGROUND: The detection of regional lymph node metastases (LNM), in particular significant LNM (≥N2), is important to guide treatment decisions in women with breast cancer. The purpose of this study was to determine whether a coronal pulse sequence as part of pre-operative breast MRI is useful to identify women without significant LNM. MATERIAL: Retrospective study between January 2017 and December 2019 on 414 consecutive women with breast cancer who underwent pre-operative breast MRI on a 1.5 T system. For lymph node (LN) staging, a coronal pre-contrast non-fat-suppressed T1-weighted TSE sequence was acquired with the system's built-in body coil, covering the chest wall; acquisition time 3:12 min. Two radiologists rated the likelihood of LNM on a 3-point scale (absent/possible/present). Validation was obtained by histology from sentinel LN biopsy, axillary LN dissection, and/or PET/CT. RESULTS: 368/414 women were staged to have no or non-significant LNM (pN0 in 282/414, pN1 in 86/414), and significant LNM (≥pN2) in 46/414. For identification of women with significant LNM, MRI was true-positive in 42/46, false-negative in 4/46, true-negative in 327/368, and false-positive in 41/83, the latter mostly caused by women with N1-disease (38/41), yielding an NPV and PPV for significant LNM of 98.8% [95%-CI: 97.0-100%] and 50.6% [43.1-58.1%], respectively. CONCLUSIONS: A 3 min coronal T1-weighted pulse sequence covering the chest wall as part of pre-operative breast MRI is useful to rule out significant LNM with high NPV. Where MRI staging is positive for significant LNM, additional work-up is indicated to improve the distinction of N1 and N2 disease.