Multiple Positive Nodes Research Articles

Incidence and distribution of contralateral lymph node metastasis associated with human papillomavirus-related oropharyngeal squamous cell carcinoma.

To analyse the rate of contralateral nodal metastasis in human papillomavirus (HPV)-associated oropharyngeal carcinoma and identify the patient cohorts that would benefit from bilateral neck treatment. A retrospective cohort review was performed on 110 HPV-positive oropharyngeal carcinoma patients who underwent transoral robotic surgery and bilateral neck dissections from 2012 to 2022. The primary outcome was to investigate the pathological incidence and location of contralateral neck node metastasis. The contralateral nodal disease rate was 12.7 per cent (n = 14), of which 2 patients (2 per cent) were occult findings, with comparable results between tongue base and tonsil sub-groups. The most commonly involved contralateral nodal station was level II (11 of 110 patients, 10 per cent). The presence of extra-nodal extension and multiple ipsilateral positive nodes was associated with increased risk of contralateral nodal disease. The incidence of contralateral nodal and occult disease in the studied cohort is low. The characteristics of patients who may benefit from bilateral neck treatment were demonstrated.

A retrospective analysis of clinical N1 oral squamous cell carcinoma

ObjectiveTo explore the appropriate dissection extent for cN1 oral cancer and to summarize neck treatment outcomes. MethodsThe cases of a series of oral squamous cell carcinoma (OSCC) patients with cN1, who underwent radical resection of the primary site and neck dissection (I-V) as the initial treatment at our institution. The distribution of pathological cervical lymph node metastases was analyzed, and the overall survival (OS), disease- specific survival (DSS) and regional control rate were estimated by the Kaplan–Meier method. ResultsPathological positive cervical lymph nodes were seen in 19 of the 57 patients. Eleven patients had one positive lymph node (pN1), whereas eight patients had multiple positive lymph nodes (pN2b). The most distal cervical metastasis was at level Ⅰ or Ⅱ in 17 cases, at level Ⅲ in one case, and at level IV in one case. There was no patient with cervical metastasis at level Ⅴ. The 5-year OS was 79.9%, the 5-year DSS was 85.3%, and the 5-year regional control rate was 87.5%. ConclusionsIn conclusion, of the 57 patients diagnosed as cN1 oral cancer, there was no patient with cervical metastasis at level Ⅴ, suggesting that level V dissection can be omitted.

Abstract PO-066: Complete pathological response following neoadjuvant chemotherapy and recurrence free survival in patients with p16-positive oropharyngeal cancer

Abstract Introduction: Locoregionally advanced p16+ squamous cell carcinoma of the oropharynx (OPSCC) is most often treated either with primary chemoradiation (CRT) or surgery followed by adjuvant treatment. Surgery alone is often insufficient treatment as adverse features such as extranodal extension, close or positive margins, lymphovascular invasion, or multiple positive lymph nodes are often identified, resulting in the need for adjuvant radiation or CRT. Primary surgery is often not pursued in more advanced cases since surgical pathology may show adverse features requiring adjuvant CRT, resulting in "triple therapy", the effects of which may worsen risk of long-term treatment toxicity. Our institution has demonstrated excellent oncologic and quality of life outcomes using a neoadjuvant chemotherapy (NAC) regimen of cisplatin and docetaxel prior to surgical treatment with TORS and neck dissection. Due to high rates of clinical-to-pathologic downstaging, adjuvant treatment is often avoided entirely. Here, we explore whether the development of a complete pathologic (pCR) response following NAC associates with 2-year recurrence free survival. Methods: A retrospective cohort study of patients receiving neoadjuvant doublet cisplatin and docetaxel followed by surgery (NAC+S) at a single institution between October 2015 and March 2023 was performed and pathologic responses and 2-year recurrence free survival was recorded following IRB exemption. Results: Fifty-four patients with p16+ OPSCC treated with NAC+S were identified. 49 patients (91%) received three cycles of NAC; 5 patients (9%) received two cycles. Comparing clinical staging to pathologic analysis of surgical specimens, 40 of 54 patients (68%) experienced clinical-to-pathologic downstaging after NAC. A pCR was identified in 23 of 54 patients (43%). Of patients that did not develop a pCR, 9 of 31 patients (29%) received adjuvant treatment due to the identification of high-risk pathologic features. Of patients that developed a pCR, 1 of 23 (4%) developed disease relapse within 2 years. Of patients that did not develop a pCR but did not require adjuvant treatment, 2 of 22 (9%) developed disease relapse within 2 years. Of patients that did not develop a pCR but did require adjuvant treatment, 2 of 9 (22%) developed disease relapse within 2 years. A trend toward reduced risk of disease relapse was observed in patients that develop a pCR following NAC compared to those that do not but did not reach statistical significance (1 of 23 relapses with pCR, 4 of 31 relapses without pCR; P>0.05, two-sided Chi-square test). Conclusion: High rates of pCR following NAC were observed in this small retrospective cohort of patients with newly diagnosed p16+ OPSCC despite 84% of patients avoiding any adjuvant treatment. Patients that develop a pCR after NAC trend toward reduced risk of recurrence compared to those that do not. The development of pCR after NAC may be a suitable short-term clinical outcome measure in prospective clinical trials of NAC for patients with newly diagnosed p16+ OPSCC. Citation Format: Alisha R. Pershad, Maxwell Madani, Timothy B. Shaver, Arjun Joshi, Clint T. Allen, Joseph F. Goodman. Complete pathological response following neoadjuvant chemotherapy and recurrence free survival in patients with p16-positive oropharyngeal cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-066.

Factors of Early Recurrence After Resection for Intrahepatic Cholangiocarcinoma.

Two-thirds of patients undergoing liver resection for intrahepatic cholangiocarcinoma experience recurrence after surgery. Our aim was to identify factors associated with early recurrence after resection for intrahepatic cholangiocarcinoma. Patients with intrahepatic cholangiocarcinoma undergoing curative intent resection (complete resection and lymphadenectomy) were included in two centers between 2005 and 2021 and were divided into three groups: early recurrence (< 12months after resection), delayed recurrence (> 12months), and no recurrence. Patients experiencing early (< 90days) postoperative mortality were excluded. Among 120 included patients, 44 (36.7%) experienced early recurrence, 24 (20.0%) experienced delayed recurrence, and 52 (43.3%) did not experience recurrence after a median follow-up of 59months (IQR: 26-113). The median recurrence-free survival was 16months (95% CI: 9.6-22.4). Median overall survival was 55months (95% CI: 45.7-64.3), while it was 25months for patients with early recurrence (p < 0.001). Patients with early recurrence had significantly larger tumors (59.1% of tumors > 70mm in early vs. 58.3% in delayed vs. 26.9% in no recurrence group, p = 0.002), multiple lesions (65.9% vs. 29.2% vs. 11.5%, p < 0.001), and positive lymph nodes (N +) (38.6% vs. 37.5% vs. 11.5%, p = 0.005). In multivariable analysis, presence of multiple lesions (OR: 9.324; 95% CI: 3.051-28.489; p < 0.001) and positive lymph nodes (OR: 3.307. 95% CI: 1.001-11.011. p = 0.05) were associated with early recurrence. Early recurrence after curative resection of intrahepatic cholangiocarcinoma is frequent and is associated with the presence of multiple lesions and positive lymph nodes, raising the question of surgery's futility in this context.

Evidence and implementation gaps in management of sentinel node–positive melanoma in the United States

BackgroundMelanoma clinical trials demonstrated that completion lymph node dissection is low value for most sentinel lymph node–positive patients. Contemporaneous trials of adjuvant systemic immunotherapy and BRAF/MEK targeted therapy showed improved recurrence-free survival in high-risk sentinel lymph node–positive patients. To better understand how oncologic evidence is incorporated into practice (implementation), we evaluated factors associated with discontinuation of completion lymph node dissection and adoption of systemic treatment at United States Commission on Cancer–accredited centers. MethodsIn a retrospective cohort study of adults with sentinel lymph node–positive melanoma treated from 2012 to 2017 using the National Cancer Database, we evaluated use of completion lymph node dissection and adjuvant systemic treatment using mixed-effects logistic regression, reporting results as odds ratios with 95% confidence intervals. ResultsAmong 10,240 sentinel lymph node–positive melanoma patients, performance of completion lymph node dissection declined from 60% to 27%. Adjuvant systemic treatment increased from 29% to 43% (37% in stage IIIA patients, 46% in IIIB–C). Completion lymph node dissection was less common with lower extremity tumors (odds ratio = 0.53, 95% confidence interval = 0.44–0.64) and more common with multiple positive sentinel lymph nodes (odds ratio = 2.36, 95% confidence interval = 2.08–2.67), treatment at a high- or moderate-volume center (odds ratiohigh = 1.49, 95% confidence interval = 1.05–2.12; odds ratiomoderate = 1.32, 95% confidence interval = 1.05–1.64), and receipt of systemic therapy (odds ratio = 1.44, 95% confidence interval = 1.27–1.63). The increased likelihood of completion lymph node dissection in patients receiving adjuvant systemic treatment persisted in the most recent study years and in patients with a single positive sentinel lymph node. ConclusionAt a population level, completion lymph node dissection declined and adjuvant systemic treatment increased, reflecting evidence-responsive care. Variation in persistent use of completion lymph node dissection and in provision of adjuvant treatment for lower risk patients highlights residual gaps in both evidence and implementation.

Oncological outcomes of total glossectomy procedure for advanced tongue cancer: a single-centre experience

Surgeons treating advanced carcinoma of the tongue with total glossectomy face many conflicts in view of the morbidity and poor functional and survival outcomes following surgery. It is pertinent to study the patients undergoing total tongue compartment resection as a separate cohort to analyse their outcomes. This study investigated the oncological outcomes of 150 patients with advanced tongue squamous cell carcinoma who underwent total glossectomy. The results suggest that compartment resection significantly improved local control, irrespective of margin status. The presence of multiple positive nodes was found to be an independent poor prognostic factor, and adjuvant radiation significantly improved survival. Total glossectomy is feasible and safe in both the primary and salvage setting and should be considered as the surgical option for advanced tongue cancer.

Central neck lymph node metastasis in oral squamous cell carcinoma at the floor of mouth

sBackgroundOur goal was to analyze the incidence of level VI metastasis in previously untreated oral squamous cell carcinoma (SCC) patients and their clinicopathological and prognostic characteristics.MethodsOral SCC patients with level VI metastasis were retrospectively enrolled, and their demographic and pathologic features as well as their survival data were descriptively analyzed.ResultsA total of 13 cases from 1875 patients were included, all patients had SCC at the floor of mouth (SCCFOM). Eight (61.5%) patients had a pT4 tumor, and all patients had a pathological N3 neck with multiple positive lymph nodes. Adverse pathologic features were present in 100% of the patients. The size of the metastatic foci in level VI ranged from 2.6 cm to 4.5 cm with a mean value of 3.2 cm, and 5 patients showed a soft tissue deposit with no lymph node component. Recurrence occurred in all patients, and 11 patients died of uncontrolled cancer within 5 years after surgery.ConclusionLevel VI metastasis in primary oral SCCFOM is rare, and its prognosis is poor.

Perineural Invasion As the Sole Pathologic Risk Factor After Surgical Resection for Head and Neck Squamous Cell Carcinoma.

IntroductionPostoperative radiotherapy (PORT) is routinely recommended for patients with head and neck squamous cell carcinoma (HNSCC) based on pathologic risk factors (pRFs) such as perineural invasion (PNI). Patients with PNI as the sole pRF after resection of HNSCC are uncommon and their prognosis is less clear. The aim of this study is to assess the role of PNI as a sole risk factor in patients with otherwise pathologically low-risk HNSCC.MethodsPatients with HNSCC of the oral cavity, pharynx, or larynx treated with primary surgical resection from 2013 to 2018 were identified from an institutional cancer registry. Those with pRFs (pathologic T3-4 disease, lymphovascular space invasion [LVSI], multiple positive lymph nodes, close [within 2 mm] or positive margins, extranodal extension [ENE], or recurrent disease) were excluded, yielding an otherwise pathologically low-risk cohort with or without incidental, pathologic PNI. Locoregional control (LRC), overall survival (OS) and disease-specific survival (DSS) were estimated and compared between PNI groups and by adjuvant therapy.ResultsA total of 1,058 patients were identified as having undergone surgical resection. Exclusion of patients with other pRFs, those with unknown PNI, and oral cavity patients with depth of invasion > 10 mm yielded a study cohort of 85 patients. Eight patients (10% of study group, <1% of all patients) had PNI as the sole pRF, none of which had clinical signs or symptoms of perineural tumor spread. The remaining 77 were negative for PNI and thus pathologically low risk. Patients with PNI were more likely to have oral cavity cancer, to be younger, and to have received PORT than those without PNI; no patient received concurrent chemotherapy. At a median follow-up of 46.4 months, two- and five-year LRC rates were 81.4% and 78.5%, respectively. No differences were noted between PNI-positive and PNI-negative groups (p=0.73) or PORT v. no-PORT groups (p=0.39). While the utility of PORT is not possible to assess given limited sample size, four patients with PNI who did not receive PORT did not experience locoregional failure. Seventeen patients overall experienced locoregional failure and 14 were ultimately salvaged. Five-year OS and DSS were 77.4% and 90.8%, respectively.ConclusionPatients with pathologically low-risk HNSCC after surgical resection experience high rates of LRC. In this large institutional cohort, PNI as the sole pRF was exceedingly rare, and the benefit of adjuvant therapies is difficult to assess. Within this limitation, PORT remains the standard of care for patients with PNI to reduce the risk of locoregional failure. Further collaborative studies are required to adequately assess the prognostic impact of PNI alone in resected HNSCC.

Outcomes of patients with metastatic cutaneous squamous cell carcinoma to the axilla: a multicentre cohort study.

Metastatic cutaneous squamous cell carcinoma to the axilla is uncommon, with limited data to guide management. We sought to assess the outcomes of patients with this condition after surgery and radiotherapy. A retrospective cohort study of patients treated at two Australian hospitals from 1994 through 2016 was performed. A total of 74 patients were identified, including 48 treated curatively with surgery-plus-radiotherapy and 15 with surgery alone. Compared with patients treated with surgery alone, a higher proportion of patients treated with surgery-plus-radiotherapy had lymph nodes larger than 6 cm (53% versus 8%, P=0.012) and multiple adverse histopathological features (75% versus 47%, P=0.04). The groups had similar 5-year disease-free survival (45% versus 46%) and overall survival (51% versus 48%). Presence of multiple positive lymph nodes was associated with reduced disease-free survival (hazard ratio 4.57, P=0.01) and overall survival (hazard ratio 3.53, P=0.02). Regional recurrence was higher in patients treated with surgery alone (38% versus 22%, P=0.22) and patients with lymph nodes larger than 6cm (34% versus 10%, P=0.03). All recurrences occurred within 2 years following treatment. Combined-modality therapy for metastatic cutaneous squamous cell carcinoma to the axilla is recommended for high-risk patients, although outcomes remain modest. The key period for recurrence is within 2 years following treatment.

Stage IIIa Melanoma and Impact of Multiple Positive Lymph Nodes on Survival

For patients with cutaneous melanoma, having >1 positive lymph node (LN) is associated with worse survival. We hypothesized that for stage IIIA patients, N2a disease (2 to 3 positive LN) would be associated with a worse prognosis compared to those with N1a disease (1 positive LN). Stage IIIA melanoma patients in the NCDB Participant User File from 2010 to 2016 were analyzed. Overall survival (OS) between N1a and N2a patients was compared. Subgroup analyses were made between patients undergoing sentinel lymph node (SLN) biopsy alone and those undergoing subsequent completion lymph node dissection (CLND). A separate post hoc analysis of T2a patients undergoing SLN biopsy and CLND from a prospective multicenter randomized clinical trial was performed to validate the findings. Records of 2,305 IIIA patients were evaluated. In an adjusted survival model, N2a disease was an independent risk factor for worse OS (hazard ratio [HR] 1.56, p= 0.0052). In the subgroup analysis, there was no difference in OS between N1a and N2a disease for patients who underwent SLN biopsy without CLND (p= 0.59), but there was a significant difference in OS for patients who underwent SLN biopsy plus CLND (p= 0.0009). The separate clinical trial database confirmed that for patients with SLN-only disease, there was no difference in OS between N1a and N2a disease. For stage IIIA melanoma patients, the distribution of micrometastatic lymph node disease (SLN or non-SLN), rather than the absolute number of SLNs, should be considered when individualizing adjuvant therapy recommendations.

Carcinoma ex pleomorphic adenoma: A review of incidence, demographics, risk factors, and survival.

Identify variables that are independent predictors of survival in carcinoma ex pleomorphic adenoma (CXPA) of the major salivary glands using a population-based database and evaluate the incidence and management strategies for this rare malignancy. The Surveillance, Epidemiology, and End Results (SEER) database was queried for all cases of major salivary gland CXPA from 1973 to 2015. Of the 619 patients identified, the parotid gland was the most common site of involvement (76.9%, 476/619). The reported incidence of CXPA has risen in the past decade (2005-2015, 0.24 to 0.63 per 1,000,000). The 2-year and 5-year disease-specific survival (DSS) rates were 90.3% and 80.4%, respectively. On univariate analysis, facial nerve sacrifice was not a statistically significant predictor of survival (HR = 1.213, 95% CI [0.588-2.058], P = 0.602). Patients with a tumor size >4 cm, multiple positive lymph nodes, and distant metastatic disease had a 2 to 4-fold statistically significant increase in mortality using a multivariate analysis. Statistical significance was not demonstrated in the DSS of patients who underwent partial versus total parotidectomy procedures. CXPA is a rare salivary malignancy that has a reported increased incidence in the last decade. Tumor size >4 cm, multiple positive lymph nodes, and distant metastatic disease are predictors of disease-specific mortality. Further research should be conducted to improve early detection and survival strategies for this salivary cancer. 4.

Predictors of extensive lymphatic dissemination and recurrences in node-positive endometrial cancer

ObjectiveTo identify predictors of extensive lymphatic dissemination and distant recurrences in node-positive endometrial cancer (EC). MethodsClinicopathologic data were collected of patients who had fully staged EC with at least 1 positive lymph node. Permanent sections of metastatic lymph nodes were reviewed; metastases were characterized according to size (≤2 mm and >2 mm) and location in the lymph node (intra- vs extracapsular). Risk of occurrence of multiple pelvic and para-aortic lymph node dissemination was calculated by combining risk factors identified at multivariate analysis. ResultsOf 96 patients, 85 had positive pelvic nodes, of whom 71 (83.5%) had high-volume metastases. In the presence of both macrometastasis in the pelvic basin (odds ratio [OR], 13.42; [95% CI, 2.44–73.83]) and uterine serosal involvement of the tumor at final pathologic evaluation (OR, 11.84 [95% CI, 1.22–115.11]), multiple pelvic node dissemination occurred in 91.7% of cases (vs 7.7% in the absence of both). Concomitant presence of pelvic macrometastasis, lymphovascular space invasion (LVSI), and extracapsular invasion led to 85.7% occurrence of para-aortic involvement (vs 11.1% if no factors present). LVSI was independently associated with nonvaginal recurrences (hazard ratio, 2.62 [95% CI, 1.33–5.16]). ConclusionsPresence of high-volume metastases in the pelvic lymph nodes is associated with concomitant presence of multiple positive pelvic nodes, as well as para-aortic node involvement. LVSI is associated with both para-aortic node involvement and occurrence of nonvaginal relapses. In this era of sentinel lymph node mapping, these factors may help predict the extent of lymphatic dissemination in EC.

Occult Nodal Disease and Occult Extranodal Extension in Patients With Oropharyngeal Squamous Cell Carcinoma Undergoing Primary Transoral Robotic Surgery With Neck Dissection

The historically reported rates of subclinical cervical nodal metastases in oropharyngeal squamous cell carcinoma (OPSCC) predate the emergence of human papillomavirus as the predominant causative agent. The rate of occult nodal disease with changing etiology of OPSCC is not known, and it is challenging to anticipate which patients will be upstaged postoperatively and will require adjuvant therapy. To assess the rate of nodal upstaging and occult extranodal extension (ENE) in a multi-institutional population of patients with pathologic (p)T1-2 OPSCC treated by transoral robotic surgery and neck dissection. This retrospective, multicenter cohort study of 92 participants at 2 US institutions (Albert Einstein College of Medicine, Bronx, New York [n = 38], and Icahn School of Medicine at Mount Sinai, New York, New York [n = 39]) and 1 Canadian institution (Princess Margaret Hospital, Toronto [n = 15]) examined the rate of postoperative pathologic upstaging for 92 patients with pT1-2 OPSCC undergoing transoral robotic surgery with neck dissection from August 2007 to December 2016. A neuroradiologist at each site blinded to final pathologic diagnosis reviewed preoperative imaging; these findings were compared with operative pathology and applied for tumor staging using the eighth edition of the American Joint Committee on Cancer Cancer Staging Manual. The statistical analysis was performed on December 18, 2018. Occult pathologic nodal disease and change in nodal category postoperatively. Of 92 patients who met the inclusion criteria, 76 (83%) were male, and they had a mean (SD) age at surgery of 59.5 (10.5) years; 70 patients (84%) with available p16 status were positive. Five of 18 patients (28%) who had no evidence of nodal disease on imaging had occult pathologic nodal disease. Seven of 32 patients (22%) presenting with no nodal disease or with a single metastatic node on imaging received pathologic upstaging because of multiple positive nodes, indicating implementation of additional adjuvant treatment not anticipated after a priori imaging. Changes included 12 patients (13%) who had pathologic nodal upstaging and 12 (13%) with pathologic nodal downstaging in the eighth edition of staging. In the cohort, 24 patients (27%) had pathologic ENE, and 5 of 39 patients (13%) had occult ENE in the absence of radiographic evidence. Predicting pathologic staging preoperatively for patients with OPSCC undergoing transoral robotic surgery and neck dissection remains a challenge. Although nodal size, tumor size, and location do not help predict ENE, the presence of nodes on imaging and nodal category may help predict ENE. Our findings suggest a small proportion of patients might benefit from further adjuvant therapies not predicted by preoperative imaging based on occult nodal upstaging and ENE.

Lymph node yield from neck dissection in HPV-associated oropharyngeal cancer.

To determine the influence of nodal yield during neck dissection on survival in surgically managed human papillomavirus (HPV)-associated oropharyngeal cancer. The National Cancer Database was used to identify patients with HPV-associated tumor T1 to T2 oropharyngeal squamous cell carcinoma who underwent upfront surgery with or without adjuvant therapy. Patients were stratified by lymph node yield (<26 vs. ≥26 nodes). Multivariable Cox proportional hazards regression analysis was used to identify factors associated with overall survival. Models were stratified by pathologically positive node number. There were 2,554 patients identified with previously untreated T1 to T2 oropharyngeal squamous cell carcinoma who underwent resection of the primary tumor and neck dissection between 2010 and 2015. Fifty-two percent had zero to one pathologically involved lymph node. Among all study patients, lymph node harvest of ≥26 was not associated with survival when adjusted for relevant covariates (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.49-1.00). However, in patients with zero to one pathologically involved node, lymph node harvest of ≥26 was significantly associated with improved overall survival (HR 0.29, 95% CI 0.20-0.78). This survival benefit was lost in patients with two or more positive nodes (2-4 positive nodes: HR 0.89, 95% CI 0.52-1.51; 5 or more positive nodes: HR 1.01, 95% CI 0.47-2.20). For patients with surgically managed early T-stage HPV-associated oropharyngeal squamous cell carcinoma, lymph node yield was not associated with survival outcomes for patients with multiple positive lymph nodes. Those with a more limited burden of regional metastatic disease, however, may benefit harvest of at least 26 nodes during neck dissection. 4 Laryngoscope, 130:666-671, 2020.

Selective Neck Dissection and Survival in Pathologically Node-Positive Oral Squamous Cell Carcinoma.

The most important prognostic factor in oral squamous cell carcinoma (OSCC) is neck metastasis, which is treated by neck dissection. Although selective neck dissection (SND) is a useful tool for clinically node-negative OSCC, its efficacy for neck node-positive OSCC has not been established. Sixty-eight OSCC patients with pN1–3 disease who were treated with curative surgery using SND and/or modified-radical/radical neck dissection (MRND/RND) were retrospectively reviewed. The neck control rate was 94% for pN1–3 patients who underwent SND. The five-year overall survival (OS) and disease-specific survival (DSS) in pN1-3 OSCC patients were 62% and 71%, respectively. The multivariate analysis of clinical and pathological variables identified the number of positive nodes as an independent predictor of SND outcome (OS, hazard ratio (HR) = 4.98, 95% confidence interval (CI): 1.48–16.72, p < 0.01; DSS, HR = 6.44, 95% CI: 1.76–23.50, p < 0.01). The results of this retrospective study showed that only SND for neck node-positive OSCC was appropriate for those with up to 2 lymph nodes that had a largest diameter ≤3 cm without extranodal extension (ENE) of the neck and adjuvant radiotherapy. However, the availability of postoperative therapeutic options for high-risk OSCC, including ENE and/or multiple positive lymph nodes, needs to be further investigated.

Survival in clinical stage I endometrial cancer with single vs. multiple positive pelvic nodes: results of a multi-institutional Italian study.

ObjectiveTo investigate survival outcomes in endometrioid endometrial cancer (EEC) patients with single vs. multiple positive pelvic lymph nodes.MethodsWe performed a retrospective evaluation of all consecutive patients with histologically proven International Federation of Gynecology and Obstetrics (FIGO) stage IIIC1 EEC who underwent primary surgical treatment between 2004 and 2014 at seven Italian gynecologic oncology referral centers. Patients with pre- or intra-operative evidence of extra-uterine disease (including the presence of bulky nodes) and patients with stage IIIC2 disease were excluded, in order to obtain a homogeneous population.ResultsOverall 140 patients met the inclusion criteria. The presence of >1 metastatic pelvic node was significantly associated with an increased risk of recurrence and mortality, compared to only 1 metastatic node, at both univariate (recurrence: hazard ratio [HR]=2.19; 95% confidence interval [CI]=1.2–3.99; p=0.01; mortality: HR=2.8; 95% CI=1.24–6.29; p=0.01) and multivariable analysis (recurrence: HR=1.91; 95% CI=1.02–3.56; p=0.04; mortality: HR=2.62; 95% CI=1.13–6.05; p=0.02) and it was the only independent predictor of prognosis in this subset of patients. Disease-free survival (DFS) and disease-specific survival (DSS) were significantly longer in patients with only 1 metastatic node compared to those with more than 1 metastatic node (p=0.008 and 0.009, respectively).ConclusionThe presence of multiple metastatic nodes in stage IIIC1 EEC represents an independent predictor of worse survival, compared to only one positive node. Our data suggest that EEC patients may be categorized according to the number of positive nodes.

Beyond Positive Margins and Extracapsular Extension: Evaluating the Utilization and Clinical Impact of Postoperative Chemoradiotherapy in Resected Locally Advanced Head and Neck Cancer.

Purpose To examine recent utilization and survival outcomes associated with use of adjuvant chemoradiotherapy (CRT) for patients with resected locally advanced head and neck cancer (LAHNC) with negative surgical margins (SM negative) and no extracapsular extension (ECE). Materials and Methods We conducted a retrospective observational cohort study using the National Cancer Database evaluating patients diagnosed in 2004 to 2012 with AJCC stage III to IVB squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx treated with definitive surgery and adjuvant radiotherapy (RT) or CRT. We identified a subset of patients with SM negative and no ECE (n = 10,870). We determined factors associated with CRT use and examined overall survival of patients receiving CRT versus RT. We further evaluated survival outcomes by number of lymph nodes involved to assess whether this was associated with benefit from CRT. Results Among patients with resected LAHNC with SM negative and no ECE, 47% received adjuvant CRT. The use of CRT varied substantially according to several factors, including patient age, contralateral/bulky neck disease, increasing number of positive lymph nodes, and lower neck disease. CRT was associated with a statistically significant improvement in overall survival compared with RT alone (hazard ratio, 0.90; 95% CI, 0.86 to 0.94; P < .001). Survival benefits of CRT versus RT alone increased in patients with multiple positive lymph nodes. Conclusion The use of adjuvant CRT in patients with resected LAHNC with SM negative and no ECE is common. Substantial practice variation as well as the survival differences observed in this study support the conduct of additional research to guide personalized treatment approaches in this setting. The number of positive lymph nodes seems to be an appropriate selection factor for further investigation of CRT in such patients.

Impact of p16 expression in oropharyngeal cancer in the postoperative setting: the necessity of re-evaluating traditional risk stratification.

To evaluate the impact of p16 expression as a surrogate marker of human papillomavirus status in oropharyngeal squamous cell carcinoma patients underwent surgery followed by postoperative radiotherapy. We identified 126 consecutive patients with histologically confirmed, newly diagnosed oropharyngeal squamous cell carcinoma who received surgery followed by radiotherapy and had p16 expression data available. All patients were treated between 2001 and 2011. Patients with high-risk factors (positive surgical margin and/or extracapsular extension) or other risk factors (multiple positive lymph nodes, perineural/lymphovascular invasion) were offered postoperative radiotherapy with or without concurrent chemotherapy. One hundred and four (82.5%) patients were p16-positive (p16 (+)) and 22 (17.5%) were p16-negative (p16 (-)). With a median follow-up of 56 months, patients with p16 (+) oropharyngeal squamous cell carcinoma exhibited a significantly better 5-year disease-free survival(80.7% vs. 57.6%, P <0.001) and overall survival(84.9% vs. 59.1%, P <0.001) than those with p16 (-) tumors. The p16 (+) oropharyngeal squamous cell carcinoma with high-risk factors (n=64) showed no difference in disease-free survival (79.7% vs. 68.3%; P =0.531) and overall survival (82.1% vs. 76.2%; P =0.964) between postoperative radiotherapy and postoperative radiotherapy with concurrent chemotherapy. Expression of p16 is a strong independent prognostic factor of survival in the postoperative setting of oropharyngeal squamous cell carcinoma. The favorable prognosis of p16 (+) oropharyngeal squamous cell carcinoma suggests a need to re-examine traditional risk stratification for determining optimal adjuvant treatment.

A clinicopathological study of perineural invasion and vascular invasion in oral tongue squamous cell carcinoma

The risk factors for recurrence of head and neck cancer are classified as being of high or intermediate risk. Those of intermediate risk include multiple positive nodes without extracapsular nodal spread, perineural/vascular invasion, pT3/T4 primary tumours, and positive level IV/V nodes. However, little evidence is available to validate these intermediate risk factors. We analyzed perineural/vascular invasion in 89 patients who underwent radical surgery for oral tongue squamous cell carcinoma, whose records were reviewed retrospectively. Perineural invasion was found in 27.0% of cases and vascular invasion in 23.6%; both had a strong relationship with histopathological nodal status (P=0.005). The 5-year disease-specific survival (DSS) and overall survival rates of patients with perineural invasion were significantly lower than those of patients without perineural invasion (P<0.001 and P=0.002, respectively). The 5-year DSS of UICC stage I and II cases with perineural/vascular invasion was significantly lower than those without (P<0.001 and P=0.008, respectively). Perineural invasion and vascular invasion are risk factors for regional metastasis and a poor prognosis. We recommend elective neck dissection when perineural/vascular invasion is found in clinical stage I and II cases. The accumulation of further evidence to consider intermediate risks is required.

The effect of surgeon experience on the detection of metastatic lymph nodes in the central compartment and the pathologic features of clinically unapparent metastatic lymph nodes: what are we missing when we don't perform a prophylactic dissection of central compartment lymph nodes in papillary thyroid cancer?

Prophylactic central neck dissection (PCND) for papillary thyroid cancer (PTC) is controversial. Recent publications suggest that the number and size of nodes and the presence of extranodal extension (ENE) are important features for risk stratification of lymph node metastases. We analyzed these features in clinically unapparent nodes that would not otherwise be removed. We also investigated the impact of surgeon experience on the ability to detect metastatic lymph nodes intraoperatively. Forty-seven patients with well-differentiated PTC, with no preoperative evidence of central metastases, were included in this study. Intraoperatively, clinically apparent disease was determined by inspection and palpation by the senior surgeon and a fellow/senior resident, and recorded in a blinded fashion. Rate of occult metastases based on intraoperative evaluation were tabulated for each group of surgeons. Histopathologic features of occult nodes were analyzed to determine what clinicians would be missing by foregoing a PCND, and how that would have impacted the patient management. The rate of occult metastases, based on senior surgeon assessment, was 26%, and did not differ significantly from fellow/senior resident assessment. The level of agreement between these two surgeon groups was moderate (k=0.665). Analysis of the false negative cases revealed that the size of the largest undetected node ranged from 0.1 to 1.3 cm; 36% of patients with occult metastases demonstrated five or more positive nodes, and 27% showed ENE. Clinical assessment based on intraoperative inspection and palpation had poor sensitivity and specificity in identifying metastatic central nodes, regardless of the level of experience of the surgeon. There was moderate agreement between surgeons of different experience levels. Sensitivity improved significantly with larger size of positive nodes, but not with the presence of multiple positive nodes or presence of ENE. In foregoing PCND in this patient population, our results suggest that treating clinicians miss potentially virulent disease with a large number of occult positive central nodes and occult nodes with ENE. This is the first report to address the pathologic features of clinically nonevident central nodes showing a high incidence of clinically relevant, adverse histologic features, as well as the impact of surgeon experience in performing the important intraoperative determination of whether there are clinically evident nodes that require removal.