N1a Disease Research Articles

Radiologic Extranodal Extension of Metastatic Lymph Nodes in Patients With Non-Small Cell Lung Cancer: Prognostic Utility and Diagnostic Performance.

BACKGROUND. Pathologic extranodal extension (ENE) in metastatic lymph nodes (LNs) has been associated with unfavorable prognosis in patients with non-small cell lung cancer (NSCLC). OBJECTIVE. The purpose of this article was to evaluate the prognostic utility of radiologic ENE and its diagnostic performance in predicting pathologic ENE in patients with NSCLC. METHODS. This retrospective study included 382 patients (mean age, 67 ± 10 [SD] years; 297 men, 85 women) diagnosed with NSCLC and clinical N1 or N2 disease between January 2010 and December 2016. Two thoracic radiologists reviewed staging chest CT examinations to record subjective overall impression for radiologic ENE (no ENE, possible/probable ENE, or unambiguous ENE), reviewing 30 examinations in consensus and the remaining examinations independently. Kaplan-Meier survival analysis and multivariable Cox proportional hazards model were used to evaluate the utility of radiologic ENE in predicting overall survival (OS). Prognostic utility of radiologic ENE was also assessed in patients with clinical N2a disease. In patients who underwent surgery, sensitivity and specificity were determined of radiologic unambiguous ENE in predicting pathologic ENE. RESULTS. The 5-year OS rates for no ENE, possible/probable ENE, and unambiguous ENE were 44.4%, 39.1%, and 20.9% for reader 1 and 45.7%, 36.6%, and 25.6% for reader 2, respectively. Unambiguous ENE was an independent prognostic factor for worse OS (reader 1: adjusted HR, 1.72, p = .008; reader 2: adjusted HR, 1.56, p = .03), whereas possible/probable ENE was not (reader 1: adjusted HR, 1.18, p = .33; reader 2: adjusted HR, 1.21, p = .25). In patients with clinical N2a disease, 5-year OS rate in patients with versus without unambiguous ENE for reader 1 was 22.2% versus 40.6% (p = .59) and for reader 2 was 27.6% versus 41.0% (p = .49). In 203 patients who underwent surgery (66 with pathologic ENE), sensitivity and specificity of radiologic unambiguous ENE for predicting pathologic ENE were 11% and 93% for reader 1 and 23% and 87% for reader 2. CONCLUSION. Radiologic unambiguous ENE was an independent predictor of worse OS in patients with NSCLC. The finding had low sensitivity but high specificity for pathologic ENE. CLINICAL IMPACT. Radiologic ENE may have a role in NSCLC staging workup and treatment selection.

Complications of Thyroid Cancer Surgery in Pediatric Patients at a Tertiary Cancer Center.

The incidence of complications and risk factors for hypocalcemia after pediatric thyroid cancer surgery has not been clearly defined in the literature because most reports fail to distinguish between benign and malignant disease. The trend away from total thyroidectomy (TT) to thyroid lobectomy in low-risk disease means there is a need to clearly define the complication profile of malignant disease. After institutional review board (IRB) approval, a retrospective chart review was undertaken at Memorial Sloan Kettering Cancer Center for pediatric patients undergoing surgery for well-differentiated thyroid cancer from 1986 to 2021. Clinicopathologic characteristics and complications were evaluated. Multivariable analysis was performed to identify factors independently associated with postoperative hypocalcemia. The study identified 307 pediatric patients with well-differentiated thyroid carcinoma (median follow-up period, 61 months). Of these patients, 69% underwent TT and 31% received a partial thyroidectomy. Among them, 40% had N0 disease, 28% had N1a disease, and 33% had N1b disease. Postoperatively, no patients experienced a neck hematoma, 1.6% had temporary unilateral vocal cord palsy (VCP), and 0.7% had permanent VCP due to recurrent laryngeal nerve (RLN) invasion. Temporary and permanent hypocalcemia occurred in respectively 32.6 % and 5.2 % of the patients. Multivariable analysis identified central neck dissection (CND) (odds ratio [OR] 3.30; p < 0.001) and N1 disease (OR 2.51; p = 0.036) as independent risk factors for temporary hypocalcemia and N stage (OR 3.64; p = 0.018) as a risk factor for permanent hypocalcemia. Pediatric thyroid cancer surgery results in low complication rates despite nodal metastases. Vocal cord paralysis is rare unless disease is found to be invading the RLN intraoperatively. Both N stage and CND are independent risk factors for hypocalcemia, helping to identify high-risk patients.

Outcomes of ATA Low-Risk Pediatric Thyroid Cancer Patients Not Treated With Radioactive Iodine Therapy.

The American Thyroid Association (ATA) Pediatric Guidelines recommend patients not receive radioactive iodine therapy (RAIT) for differentiated thyroid cancer (DTC) confined to the thyroid. Since publication, there is ongoing concern whether withholding RAIT will result in a lower rate of remission. This study explores whether ATA low-risk patients treated with and without RAIT achieved similar remission rates. Medical records of patients <19 years old diagnosed with DTC and treated with total thyroidectomy between 2010 and 2020 were reviewed. Multivariate logistic regression was performed to evaluate factors influencing RAIT administration and remission rate. Ninety-five patients with ATA low-risk DTC were analyzed: 53% (50/95) and 47% (45/95) were treated with and without RAIT, respectively. RAIT was used to treat 82% of patients before 2015 compared with 33% of patients after 2015 (P < .01). No significant difference in 1-year remission rate was found between patients treated with and without RAIT, 70% (35/50) vs 69% (31/45), respectively. With longer surveillance, remission rates increased to 82% and 76% for patients treated with and without RAIT, respectively. Median follow-up was 5.8 years (IQR 4.3-7.9, range 0.9-10.9) and 3.6 years (IQR 2.7-6.6; range 0.9-9.3) for both cohorts. No risk factors for persistent or indeterminate disease status were found, including RAIT administration, N1a disease, and surgery after 2015. Withholding RAIT for pediatric patients with ATA low-risk DTC avoids exposure to radiation and does not have a negative impact on remission rates. Dynamic risk stratification at 1-year after initial treatment is a suitable time point to assess the impact of withholding RAIT for these patients.

The role of prophylactic central compartment neck dissection in patients with T1-T2 cN0 papillary thyroid carcinoma.

It remains controversial whether prophylactic central compartment neck dissection (pCCND) is necessary in cases of stage T1-T2 cN0 papillary thyroid carcinoma (PTC). Some studies have demonstrated the benefits of pCCND on oncologic outcomes, whereas others reported that any advantages were insignificant. The purpose of this study was to investigate the effects of pCCND on cancer recurrence and its pattern in patients with T1-T2 cN0 PTC. We retrospectively reviewed 2,902 patients with PTC who had undergone thyroidectomy between 2006 and 2012 at Seoul St. Mary's Hospital: 2,099 patients had undergone pCCND and thyroidectomy (pCCND group), whereas 803 did not undergo pCCND (non-pCCND group). We investigated the effects of pCCND on cancer recurrence by comparing these two groups. Recurrence was classified according to the location of the recurrence. The mean follow-up period was 112 months. The mean patient age was significantly younger in the pCCND group than in the non-pCCND group. There were no statistically significant differences in the distribution of sex, tumor size, or thyroidectomy extension between the groups. In the pCCND group, 883 (42%) patients showed evidence of N1a disease, and the mean number of metastatic lymph nodes was 1.26±2.2. Recurrence occurred in 67 (2.3%) patients in the total cohort. Recurrence was observed in 20 (2.5%) and 47 (2.2%) patients in the non-pCCND and pCCND groups, respectively, but there were no significant differences between the groups (P=0.687). When analyzed by the site of recurrence, 50% and 4.3% of recurrent disease in the non-pCCND and pCCND groups, respectively, occurred in the central compartment (P<0.001). There were no differences between the two groups in recurrent disease at other sites. The 15-year cumulative central compartment recurrence-free survival (RFS) rates of patients in the non-pCCND and pCCND groups were 99% and 100%, respectively (P<0.001). In the multivariate analysis, not performing pCCND was the only independent risk factor related to central compartment RFS, and the hazard ratio was 13.362 [95% confidence interval (CI): 2.928-60.986; P<0.001]. The omission of pCCND was found to be an independent risk factor for recurrence in the central compartment in patients with T1-T2 cN0 PTC.

Patient's age with papillary thyroid cancer: Is it a key factor for cervical lymph node metastasis?

BackgroundAge is one of the important prognostic indicators of papillary thyroid cancer (PTC). However, the distinct metastatic patterns and prognosis of age-related lymph node metastasis (LNM) are unclear. This study aims to investigate the impact of age on LNM. MethodsWe conducted two independent cohort studies to assess age–nodal disease association using logistic regression analysis and a restricted cubic splines model. A multivariable Cox regression model was utilized to test the impact of nodal disease on cancer-specific survival (CSS) after age stratification. ResultsFor this study, we included 7572 and 36,793 patients with PTC in Xiangya and SEER cohorts, respectively. After adjustment, advanced age was linearly associated with decreasing risk of central LNM. Patients of age ≤18 years (OR = 4.41, P < 0.001) and 19–45 years (OR = 1.97, P = 0.002) had a higher risk of developing lateral LNM than patients of age >60 years in both cohorts. Furthermore, CSS is significantly reduced in N1b disease (P < 0.001), not N1a disease, regardless of age. The incidence of high-volume LNM (HV-LNM) was significantly higher in patients of age ≤18 years and 19–45 years than in those of age >60 years (P < 0.001), in both cohorts. In addition, CSS was compromised in patients with PTC of age 46–60 years (HR = 1.61, P = 0.022) and those of age >60 (HR = 1.40, P = 0.021) after developing HV-LNM. ConclusionsPatient age is significantly associated with LNM and HV-LNM. Patients with N1b disease or patients with HV-LNM of age >45 years have significantly shorter CSS. Age can, thus, be a useful guide for determining treatment strategies in PTC.

Validation of the TNM-8 AJCC classification for HPV-positive oropharyngeal cancers in patients undergoing trans-oral robotic surgery.

High-risk human papillomaviruses (HPV) are associated with some oropharyngeal squamous cell carcinomas (OPSCC). HPV-OPSCC have better survival outcomes compared to HPV negative tumours. The new TNM-8 AJCC staging (2018) is based on ICON-S data with 98% of patients treated with primary chemoradiation. To validate the TNM-8 AJCC classification in HPV-OPSCC treated primarily with surgery (trans-oral robotic surgery or open). There were 102 patients with HPV-OPSCC treated between July 2009 and December 2014 at the Royal Adelaide Hospital. The median age was 57years (range: 38-83) and mostly males (84.5%). 27.2% were active smokers and 50.5% reformed smokers. Early T-stage cancer in 72.8%. Primary treatment was surgery & adjuvant therapy (70%) while primary chemoradiation (30%). Survival analyses were performed for the 7th and 8th AJCC systems. The reclassification to the AJCC 8th edition staging system resulted in a change of 54 patients from stage 4 to stages 1 and 2. This was mainly an effect of changes with N2a and N2b nodal disease being reclassified to N1. Survival outcomes were comparable with the ICON-S data. The new TNM-8 classification is, therefore, validated in a cohort treated, predominantly, with primary surgery and adjuvant therapy.

Association of Unilateral Radiotherapy With Contralateral Lymph Node Failure Among Patients With Squamous Cell Carcinoma of the Tonsil

Ipsilateral neck radiotherapy (RT) is controversial in some patients with tonsil cancer due to concern for nodal failure within the contralateral nonirradiated neck (hereinafter referred to as contralateral neck failure [CNF]). To determine the rate of CNF following ipsilateral neck RT in patients with tonsil cancer. Databases including PubMed, Embase, Web of Science, and Cochrane Library were queried for peer-reviewed, English language articles published between January 1, 1980, and December 31, 2021. Studies reporting rates of CNF from at least 20 patients treated with ipsilateral neck RT. Studies were excluded if they lacked full text, reported results from databases or systematic reviews, or did not provide RT details. Data were extracted following the PRISMA reporting guideline. Study quality was assessed using criteria from a methodological index for nonrandomized studies. Pooled outcomes were estimated using random-effects models. Primary outcome was the pooled rate of CNF following ipsilateral neck RT. Secondary outcomes were the pooled rates of CNF by tumor and nodal staging categories from the 7th edition of the AJCC Cancer Staging Manual and rates of toxic effects. A total of 17 studies (16 retrospective and 1 prospective) including 1487 unique patients were identified. The pooled risk of CNF was 1.9% (95% CI, 1.2%-2.6%). The rate of CNF by tumor (T) category was as follows: 1.3% (95% CI, 0.3%-2.3%) for T1; 3.0% (95% CI, 1.6%-4.4%) for T2; 11.3% (95% CI, 3.3%-19.2%) for T3; and 16.0% (95% CI, -7.8% to 39.8%) for T4. Patients with T3 to T4 tumors had a significantly higher rate of CNF than those with T1 to T2 tumors (11.5% [95% CI, 3.9%-19.1%] vs 1.8% [95% CI, 1.0%-2.6%]; P < .001). The rate of CNF by nodal (N) category was 1.2% (95% CI, 0.1%-2.2%) for N0; 4.8% (95% CI, 2.4%-7.2%) for N1; 3.1% (95% CI, 0.4%-5.8%) for N2a; 3.1% (95% CI, 1.2%-4.9%) for N2b; and 0 (95% CI, not applicable) for N3. Rates of CNF were similar for patients with N2b to N3 and N0 to N2a disease (3.0% [95% CI, 1.2%-4.7%] vs 1.7% [95% CI, 0.6%-2.8%], respectively; P = .07). Compared with bilateral RT, ipsilateral RT was associated with increased risk of CNF (log odds ratio, 1.29 [95% CI, 0.09-2.48]; P = .04). The crude rates of xerostomia of grade 3 or greater and feeding tube use were 0.9% (95% CI, -0.2% to 1.9%) and 13.3% (95% CI, 8.3%-18.3%), respectively. In this systematic review and meta-analysis, ipsilateral neck RT was associated with a low rate of CNF in patients with small, lateralized tonsil cancers. Bilateral neck RT was associated with lower risk of CNF compared with ipsilateral neck RT. Patients with tumors of a higher T category were at increased risk for CNF following ipsilateral neck RT, and advanced nodal stage was not associated with CNF. Rates of toxic effects appeared favorable in patients treated with ipsilateral neck RT.

Sentinel lymph node biopsy in women over 70: Evaluation of rates of axillary staging and impact on adjuvant therapy in elderly women

BackgroundThe 2016 Society of Surgical Oncology Choosing Wisely guidelines recommended against routine sentinel lymph node biopsy in women ≥70 years old with favorable, early-stage breast cancer, as sentinel lymph node biopsy does not decrease recurrence or mortality in these patients. This study’s objective was to evaluate the use of sentinel lymph node biopsy and its effect on management in elderly patients. MethodsA retrospective analysis of female patients ≥70 years old with stage I–II, clinically node-negative, hormone-receptor positive, HER2-negative disease undergoing upfront breast cancer surgery between 2017 and 2019. Primary outcome was rate of sentinel lymph node biopsy. Secondary outcome was effect of sentinel lymph node biopsy on adjuvant therapy. ResultsIn total, 142 patients were included. Median age was 76 (interquartile range 73–81), and 71.8% underwent lumpectomy. On final pathology, 57.7% had invasive ductal carcinoma, and median tumor size was 15 mm (interquartile range 10–24.3). A total of 118 patients (83.1%) underwent sentinel lymph node biopsy; of these, 27 (22.9%) were positive for N1mi (7 patients) or N1a disease (20 patients). On multivariate regression analysis, patients undergoing sentinel lymph node biopsy were more likely to be younger (odds ratio 0.87, 95% confidence interval 0.78–0.95). The major risk factor for sentinel lymph node biopsy positivity was lymphovascular invasion (odds ratio 13.4, 95% confidence interval 4.57–40.1). Patients with sentinel lymph node biopsy positivity were more likely to receive local adjuvant radiation therapy (odds ratio 4.66, 95% confidence interval 1.49–16.8) and tended to receive more adjuvant regional radiation therapy (75.0% if sentinel lymph node biopsy positive compared with 15.3% if sentinel lymph node biopsy negative, P < .001). ConclusionDespite the 2016 Choosing Wisely guidelines, more than 80% of patients ≥70 years old underwent sentinel lymph node biopsy at our institution. If sentinel lymph node biopsy was positive, this is associated with over 4-fold higher rates of adjuvant radiation therapy.

Late Breaking Abstracts

Late Breaking Abstracts

Can Cervical Lymph Node Metastasis Increase the Risk of Distant Metastasis in Papillary Thyroid Carcinoma?

BackgroundDistant metastasis (DM) is a rare event and has a negative effect on the prognosis for papillary thyroid carcinoma (PTC). The relationship between cervical lymph node metastasis and DM is complicated and unclear. This study aimed to evaluate the impact of N stage subclassification on different distant metastasis sites based on age stratification, especially for patients with papillary thyroid microcarcinoma.MethodsA total of 28,712 patient with PTC cases between 2010 and 2018 were extracted from the Surveillance, Epidemiology, and End Results database. Multivariable logistic regression analysis was utilized to adjust for confounding variables. Risk stratification, including positive lymph node number and lymph node ratio, was established by receiver operating characteristic curves to help predict DM.ResultsLung was the most common metastatic site regardless of N0, N1a disease, or N1b disease. As the N stage increased, the higher the rate of DM identified. After age stratification, only N1b disease significantly increased the risk of lung metastasis (LM; odds ratio, OR = 20.45, P < 0.001) rather than bone metastasis (BM; OR = 3.46, P > 0.05) in younger patients. However, in older patients, N1b disease significantly increased the risk of both LM (OR = 4.10, P < 0.001) and BM (OR = 2.65, P = 0.007). In patients with papillary thyroid microcarcinoma (PTMC), N1a disease did not increase the risk of DM, LM, and BM compared with N0 disease (P > 0.05). Furthermore, combined N stage with risk stratification has well performance in predicting DM (area under the curve, AUC = 0.761). Similar results were shown in PTC patients with LM (AUC = 0.770) and BM (AUC = 0.729).ConclusionOverall, the incidence of DM significantly increased with the progress of N disease after age stratification. N1a disease did not increase the risk of DM in PTMC patients, regardless of LM or BM. Combined N stage with risk stratification may be beneficial for DM prediction.

Evaluating the impact of the degree of extranodal extension on outcomes in locally advanced oral cavity cancer.

e18058 Background: The presence of extranodal extension (ENE) in oral cavity cancer is associated with a higher risk of distant metastasis and worse overall survival (OS). Trials show that patients with locally advanced head and neck cancer and ENE benefit from concurrent chemoradiation over radiation therapy alone.We explored whether degree of ENE impacts survival outcomes in individuals with oral cavity cancer. Methods: From an IRB-approved database of 303 pts with locally advanced oral cavity cancer treated with surgical resection between 2001-2020, patients with pathologic ENE who received adjuvant treatment were included. Patient demographics, tumor staging, treatment information, disease recurrence, and survival were collected. Surgical slides were reviewed to confirm the extent of ENE. All staging was updated to AJCC 8th edition. Cox proportional hazards regression was used to relate patient, tumor, or treatment characteristics with either disease-free survival (DFS, composite of disease recurrence and death) or OS, from the time of radiation therapy completion. ENE was analyzed as both a dichotomous variable (major if &gt; 2 mm, minor if ≤2 mm) and as a continuous variable in the subset of patients for whom exact ENE extent could be confirmed. Results: A total of 113 patients were identified who underwent surgery and adjuvant therapy for advanced oral cavity cancer with ENE, with 35 having major ENE and 78 having minor ENE. Forty-one patients had T1-T2 disease while 72 had T3-T4 disease. Additionally, 24 had N2a disease and 89 had N3b disease. Of these, 78 received concurrent chemoradiation while 35 received radiation therapy alone. Ninety-nine patients had pathologic slides available for review to determine exact ENE extent. Median ENE distance was 1 mm (IQR 1-2, range 0.1-10). With a median follow up time of 22.3 months, there were 48 recurrences and 67 deaths. Median DFS was 21.3 months (95%CI 11.1-33.2) and median OS was 29.9 months (95%CI 20.6-66.6). Between major vs minor ENE, there was no statistically significant difference in DFS (HR 1.18, 95%CI 0.72-1.92, p = 0.51) or OS (HR 1.17, 95%CI 0.70-1.96, p = 0.55). Furthermore, there was no statistically significant association between ENE as a continuous variable and DFS (HR 0.97 per mm, 95%CI 0.87-1.4, p = 0.96) or OS (HR 0.96 per mm, 95%CI 0.83-1.11, p = 0.58). The benefit of concurrent chemotherapy on OS was not seen (HR 0.74, 95%CI 0.44-1.22, p = 0.24), though those patients on average had more advanced nodal disease (85% N3b vs 66%). Conclusions: No significant relationship was seen between extent of ENE and DFS or OS in individuals with locally advanced oral cavity cancer. This analysis was limited by the small number of patients, that most patients had ≤2 mm of ENE, and the presence of confounding risk factors such as nodal stage and receipt of chemotherapy. Overall, the effect of the degree of ENE on outcomes in advanced oral cavity cancer remains unclear.

Clinical Utility of Multigene Profiling Assays in Early-Stage Invasive Breast Cancer: An Ontario Health (Cancer Care Ontario) Clinical Practice Guideline.

Objective: The purpose of this guideline is to determine the clinical utility of multigene profiling assays in individuals with early-stage invasive breast cancer. Methods: This guideline was developed by Ontario Health (Cancer Care Ontario)’s Program in Evidence-Based Care (PEBC) through a systematic review of relevant literature, patient- and caregiver-specific consultation and internal and external reviews. Recommendation 1: In patients with early-stage estrogen receptor (ER)-positive/human epidermal growth factor 2 (HER2)-negative breast cancer, clinicians should consider using multigene profiling assays (i.e., Oncotype DX, MammaPrint, Prosigna, EndoPredict, and the Breast Cancer Index) to help guide the use of systemic therapy. Recommendation 2: In patients with early-stage node-negative ER-positive/HER2-negative disease, clinicians may use a low-risk result from Oncotype DX, MammaPrint, Prosigna, EndoPredict/EPclin, or Breast Cancer Index assays to support a decision not to use adjuvant chemotherapy. Recommendation 3: In patients with node-negative ER-positive/HER2-negative disease, clinicians may use a high-risk result from Oncotype DX to support a decision to offer chemotherapy. A high Oncotype DX recurrence score is capable of predicting adjuvant chemotherapy benefit. Recommendation 4: In postmenopausal patients with ER-positive/HER2-negative tumours and one to three nodes involved (N1a disease), clinicians may withhold chemotherapy based on a low-risk Oncotype DX or MammaPrint score if the decision is supported by other clinical, pathological, or patient-related factors. Recommendation 5: The evidence to support the use of molecular profiling to select the duration of endocrine therapy is evolving. In patients with ER-positive disease, clinicians may consider using a Breast Cancer Index (H/I) high assay result to support a decision to extend adjuvant endocrine therapy if the decision is supported by other clinical, pathological, or patient-related factors.

Thyroid Lobectomy for T1 Papillary Thyroid Carcinoma in Pediatric Patients

The current recommendation for pediatric patients with papillary thyroid cancer (PTC) is a total thyroidectomy. This recommendation applies to all stages of PTC, including papillary thyroid microcarcinoma (≤1 cm, T1a) tumors. To evaluate the characteristics of American Joint Committee on Cancer T1 PTC tumors in a large pediatric population and to identify a subgroup of patients who may benefit from a thyroid lobectomy instead of a total thyroidectomy. This retrospective cohort study was conducted from January 1, 2009, to May 31, 2020. The study took place at a tertiary care medical center and included 102 patients who were surgically treated for T1 PTC: 52 with stage T1a (≤1 cm) tumors and 50 with stage T1b (>1 cm but ≤2 cm) tumors. Primary outcomes included the presence of bilateral disease and lymph node metastasis. A total of 102 patients (mean age, 15.3 years [range, 9.7-18.9 years]; 84 girls [82.4%]) were included in the analysis. Among 52 patients with T1a tumors, 10 (19.2%) had bilateral disease, and 15 (28.8%) had central neck lymph node (N1a) metastasis. Among 50 patients with T1b tumors, 10 (20%) had bilateral and 13 (26%) had N1a disease. Of those with T1a, unilateral multifocality was associated with bilateral disease (odds ratio [OR], 2.1; 95% CI, 1.3-3.4) and N1a disease (OR, 5.1; 95% CI, 1.5-17.6). Both N1a disease (OR, 20.0; 95% CI, 3.5-115.0) and ≥4 positive lymph nodes (OR, 8.6; 95% CI, 1.2-60.9) were associated with bilateral disease. In patients with no pathologic evidence of lymph node metastasis (N0), there was a 95% rate of unilateral PTC. In patients with T1b tumors, unilateral multifocality was also associated with bilateral disease (OR, 1.8; 95% CI, 1.3-2.7). Patients with T1b tumors had an increased risk of lateral (N1b) neck lymph node metastasis when compared with those with T1a tumors (OR, 3.7; 95% CI, 1.0-14.5). The findings of this cohort study suggest that, in patients with unifocal T1a PTC without clinically evident nodal disease on preoperative ultrasonography, a thyroid lobectomy and central neck dissection may be considered. If there is no evidence of unilateral multifocality or if there are fewer than 4 positive lymph nodes on postoperative pathology, then close observation may be considered. These findings have substantial clinical implications and may result in practice changes regarding the extent of thyroid surgery on low-stage pediatric PTC.

Validation of the TNM-8 AJCC Classification for HPV-Positive Oropharyngeal Cancers in Patients Undergoing Trans-Oral Robotic Surgery (TORS)

High-risk human papillomaviruses (HPV) are associated with some oropharyngeal squamous cell carcinomas (OPSCC) and confer a significant prognostic factor. HPV-OPSCC have better survival outcomes compared to HPV negative tumours. The new TNM-8 AJCC staging (2018) is specific to HPV-associated OPSCC. In the re-classification study by the ‘International Collaboration on Oropharyngeal Cancer Network for Staging’, 98% of HPV-OPSCC patients were treated with primary chemo-radiation. The aim of our study was to validate the TNM-8 AJCC classification in HPV-OPSCC treated primarily with surgery (trans-oral robotic surgery or open). There were 102 patients with HPV-OPSCC treated between July 2009 and December 2014 at the Royal Adelaide Hospital. The median age was 57 years (range: 38-83) and mostly males (84.5%). 27.2% were active smokers and 50.5% reformed smokers. Early T stage cancer accounted for 72.8% (T1/2). Primary treatment was with surgery (TORS or open) and adjuvant therapy (70%) while primary chemo-radiation was the treatment for 30% of patients. Kaplan-Meier and Cox regression analyses were performed for both the 7th and 8th AJCC staging systems. The re-classification of this cohort to the AJCC 8th edition staging system resulted in a change of 54 patients from stage 4 to stages 1 and 2. This was mainly an effect of changes with N2a and N2b nodal disease being reclassified to N1 and demonstrates the prognostic effect of HPV in OPSCC. Survival outcomes were comparable with the ICON-S data. The new TNM-8 classification is therefore validated in a cohort treated, predominantly with primary surgery and adjuvant therapy. Funding Statement: None. Declaration of Interests: All authors declare no conflicts of interest. Ethics Approval Statement: Ethical approval was obtained from the CALHN REC, South Australia (Ref 13,407) to analyse clinical data on TORS.

Pre-Operative Antithyroid Antibodies in Differentiated Thyroid Cancer

ObjectiveTo evaluate the significance of antithyroglobulin and antithyroid peroxidase antibody levels associated with locoregional metastatic disease in patients with well-differentiated thyroid cancer. MethodsPatients underwent initial treatment for well-differentiated thyroid cancer at our institution between 2014 and 2018. The following variables were collected: age, sex, pre-operative thyroid-stimulating hormone, thyroglobulin, antithyroglobulin antibody (TgAb), antithyroid peroxidase antibody (TPOAb), the extent of surgery, T-stage, N-stage, extrathyroidal extension (ETE), extranodal extension (ENE), lymphovascular invasion, and multifocal disease. The relationships between disease status and pre-operative TPOAb, TgAb, thyroglobulin, and thyroid-stimulating hormone were analyzed. ResultsA total of 405 patients (mean age, 52 years) were included in the study, of which 66.4% were women. Elevated TgAb was associated with the presence of lymph node metastases (LNM) in both the central and lateral neck (P < .01), with a stronger correlation to N1b versus N1a disease (P = .03). The presence of ETE was inversely related to the TgAb titer (P = .03). TPOAb was associated with a lower T-stage (P = .04), fewer LNM (P = .04), and a lower likelihood of ETE (P = .02). From multivariable analysis, TgAb ≥40 IU/mL was an independent predictive factor for a higher N-stage (P < .01 for N0 vs N1; P = .01 for N1a vs N1b), and ENE (P < .01). TPOAb ≥60 IU/mL was associated with a lower T-stage (P = .04 for T <3) and absence of ETE (P = .01). ConclusionElevated pre-operative TgAb was an independent predictor of nodal metastases and ENE, while elevated TPOAb was associated with a lower pathologic T- and N-stage. Pre-operative antithyroid antibody titers may be useful to inform the disease extent and features.

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.

Abstract P2-14-20: The impact of recurrence score versus sentinel lymph node biopsy on treatment decisions in early breast cancer

Abstract Rationale: Choosing Wisely: In an era of genomic medicine, what role does nodal information play in decisions regarding adjuvant chemotherapy for early-stage, hormone receptor-positive breast cancer ? Authors: Fowler RL, Lew KP, Dizon DS, Ciambella CC, Wakeley M, Taneja C, Wiggins DL, Lopresti ML, Constantinou M, Strenger R, Wang Y, Fenton MA, Graves TA. BACKGROUND/OBJECTIVES: For women with hormone receptor-positive (HR+) breast cancer, the Recurrence Score (RS) informs prognosis and impacts treatment decisions; whether and to what degree nodal information impacts these decisions is not clear. We conducted a retrospective review of patients with newly diagnosed HR+ early stage breast cancer who underwent a sentinel lymph node biopsy (SLNB) and had the RS obtained to discriminate the impact both evaluations had on the use of adjuvant chemotherapy. We hypothesized that for these patients, the RS supersedes nodal information in determining adjuvant treatment. METHODS: 416 patients with T1 to T2 breast cancers seen at our multidisciplinary clinic between 2013 and 2017 were identified. Data collected included demographics, node stage, RS, and adjuvant therapies. RS was stratified in to High, Intermediate, and Low Risk according to criteria used in the TAILORx trial. Continuous variables were analyzed using descriptive statistics and categorical variables were analyzed by Chi-Square or Fisher’s Exact Test. All statistics were performed using STATA 15.0. RESULTS: For this cohort, the median age was 59 years (range 27-79). The vast majority (94%) underwent initial surgical excision or mastectomy with SLNB. Of these, 338 patients (81%) had node-negative disease. Of the remaining, 37 patients (8.9%) had micro-metastasis to a single node, 39 (9.3%) had N1a disease, including one patient with 3 positive lymph nodes. RS risk was characterized as high, intermediate, and low in 12, 65, and 23%, respectively. On multivariate analysis, only age at diagnosis (p&amp;lt;0.05) and RS (p&amp;lt;0.0005) were significantly associated with the use of adjuvant chemotherapy; nodal status was not significant (p&amp;gt;0.05). CONCLUSIONS: For women with early-stage, clinically node-negative, HR+ breast cancer, the RS and age of the patient was associated with the administration of adjuvant chemotherapy. Although these data are limited to recommendations surrounding adjuvant chemotherapy and not decisions surrounding adjuvant radiation therapy, these data support the Choosing Wisely™ campaign against routine use of SLNB in low-risk patients. Citation Format: Rachel L Fowler, Kaitlyn P Lew, Don S Dizon, Chelsey C Ciambella, Michelle Wakeley, Charu Taneja, Doreen L Wiggins, Mary L Lopresti, Maria Constantinou, Rochelle Strenger, Yihong Wang, Mary A Fenton, Theresa Graves. The impact of recurrence score versus sentinel lymph node biopsy on treatment decisions in early breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-14-20.

Lymph node characteristics of 6279 N1 differentiated thyroid cancer patients.

PurposeThis study examined the clinicopathological characteristics of 6279 N1 differentiated thyroid cancer (DTC) patients who underwent operations in our center.MethodsThis was a retrospective longitudinal analysis. We categorized the DTC patients on the basis of various lymph node (LN) characteristics. Logistic regression models and multiple linear regression models were used for the correlation analysis.ResultsA total of 3693 (58.8%) N1a patients and 2586 (41.2%) N1b patients were included. Patients with N1b disease had larger metastatic foci (0.5 vs 0.15 cm), a greater number of metastatic LNs (5 vs 2), a greater number of dissected LNs (25 vs 7), and a smaller lymph node ratio (NR, number of positive LNs/number of sampled LNs) (23.1% vs 28.6%) than patients in stage N1a. Comparing the clinicopathological features, we found that male, increased tumor size, multifocality, and thyroiditis increased the risk of stage N1b disease (P < 0.05). Sex, multifocality, capsular infiltration, and tumor size were associated with the size of the metastatic LNs (P < 0.05). Sex, capsular infiltration, and nodular goiter were associated with the NR (P < 0.05). Female sex, tumor located in inferior lobe, maximal tumor diameter (MTD) < 1 cm, and nodular goiter were independent predictors for skip metastases (P < 0.05). MTD > 1 cm, central neck metastasis and age were independent predictors for bilateral lateral neck metastasis (BLNM) (P < 0.05).ConclusionThe LN characteristics of stage N1a and N1b disease were associated with significantly different features, such as sex, tumor size, multifocality, capsular infiltration, and nodular goiter.

Extent of thyroid surgery for clinically node-negative papillary thyroid carcinoma with confirmed nodal metastases after prophylactic central neck dissection: a 15-year experience in a single center.

PurposeThe use of prophylactic central neck dissection (PCND) and the extent of thyroid surgery in clinically node-negative (cN0) papillary thyroid carcinoma (PTC) are controversial. This study aimed to investigate whether the extent of thyroid surgery influences the prognosis of patients with PTC with central lymph node metastasis (N1a), which was cN0 but pathologically confirmed after PCND.MethodsThis was a single-center retrospective study using medical records. Patients who underwent thyroid surgery with PCND for the treatment of PTC between 2004 and 2019 were included. Predictive factors and local recurrence rates were analyzed.ResultsOf 2,274 patients with cN0 PTC, 436 were confirmed to have pathologic N1a disease after PCND. Among them, 340 patients (78.0%) underwent total thyroidectomy (TT) and 96 patients (22.0%) underwent less than TT. Of the 374 patients who were followed up for >6 months, 5 (1.3%) experienced recurrence. The 15-year recurrence-free survival (RFS) rate was 98.2%. No clinicopathologic factor was predictive of tumor recurrence. RFS tended to be lower in patients who underwent less than TT than in those who underwent TT; however, the difference was not statistically significant.ConclusionOur study showed low recurrence rates in patients with cN0 PTC pathologically confirmed as N1a after PCND. The RFS did not differ according to the extent of thyroid surgery. Considering the low recurrence rate and the surgical morbidity associated with thyroid surgery, less than TT with PCND may be considered for patients with cN0 unilateral PTC even with a pathologic staging of N1a after PCND.

Invasiveness and Metastatic Aggressiveness in Small Differentiated Thyroid Cancers: Demography of Small Papillary Thyroid Carcinomas in the Swedish Population

BackgroundThe western world is seeing a rising incidence of thyroid cancer. Improved diagnostic methods do not entirely explain this increase. Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid cancer. Small PTC (≤20 mm) and especially papillary thyroid microcarcinomas (PTMC ≤10 mm) are considered to be low-risk tumors but some cases are considerably more aggressive. Sufficient understanding of these mechanisms is a long-term goal for more efficient and safer treatment of these tumors.MethodsWe identified 959 cases of small PTCs in the validated Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal Surgery, grouped according to lymph node metastasis. These were analyzed according to age, gender, tumor size and geographic region.ResultsPatients with N1b disease (lateral lymph nodes metastases) had a smaller tumor size compared to patients with N1a disease (8.6 mm vs 10.1 mm respectively, p < 0.05). Patients and specifically females with N1b disease were younger than those with N0 or N1a disease. Patients with N1b disease had a lower proportion of females (60%) compared to N0 and N1a groups (81% and 78%, respectively). The incidence of operated small PTCs and of lymph node engagement differs between geographic regions in Sweden.ConclusionsSmall PTC and especially PTMC seem to show different patterns of aggressiveness and demography regarding lateral lymph node metastases and 7% had N1b disease and tumor <1 cm, underscoring the importance of lymph node evaluation in PTMC patients. More understanding of predictive factors, mechanisms for metastatic disease and causes of regional differences, is needed.