Regional Recurrence In Patients Research Articles

Abstract P3-05-06: Prognostic impact of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis-related liver fibrosis on postoperative long-term outcomes of breast cancer

Abstract Background: Obesity, the modern ‘epidemic’, has shared correlation with fatty liver disease and breast cancer. However, previous studies on the relation between fatty liver and breast cancer have shown conflicting results on the impact of fatty liver on the survival and recurrence of breast cancer patients. And there was no attempt to find out the effect of liver fibrosis, which is the consequence of fatty liver disease, on female breast cancer patients. So we attempted to investigate the prognostic value of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis(NASH)-related liver fibrosis in patients with breast cancer undergoing surgery, using noninvasive tools like liver-to-spleen attenuation(L/S) ratio and Fibrosis-4(FIB-4) score, respectively. Methods: A total of 933 patients diagnosed with primary invasive breast cancer and receiving surgery at the university-affiliated referral center between April 2006 and December 2019 were included. After excluding patients who had significant alcohol consumption and hepatitis viral infection,838 patients were divided into two groups according to the L/S ratio of 1 measured by the preoperative low-dose computed tomography: 91 patients(10.9%) with a L/S ratio< 1 vs 747 patients(89.1%) with a L/S ratio≥1. They were also divided into two groups based on the FIB-4 score of 2.67: 804 patients (95.9%) with a FIB-4 score< 2.67 vs 34 patients (4.1%) with a FIB-4 score≥2.67. The Cox proportional hazards model was used to calculate the hazard ratio (HR) and the 95% confidence interval (CI). Results: Patients with NAFLD were older, had higher BMI, and had a higher proportion of mastectomy and hyper-transaminasemia. They showed worse overall, disease-free, and regional recurrence-free survivals compared to those without NAFLD (p=0.008, 0.043, and 0.017, respectively), but no significant differences in local recurrence-free, systemic recurrence-free, and contralateral breast cancer-free survivals. The survival outcome of breast cancer did not show any relationship with NASH-related liver fibrosis (overall survival; p=0.061, disease-free survival; p=0.557). NAFLD was a significant risk factor for mortality in multivariable analysis (HR, 2.077; 95% CI, 1.052–4.102; p=0.035). After stratifying for subtypes of breast cancer, the L/S ratio remained a significant predictor of overall, disease-free, local recurrence-free, and regional recurrence-free survivals in only the hormone receptor-positive/HER2−negative subtype (p=0.007, 0.005, 0.009, and < 0.001, respectively). Conclusion: NAFLD is significantly associated with decreased overall survival, disease-free survival and increased regional recurrence in patients with breast cancer especially the hormone receptor-positive/HER2−negative subtype. NASH-related fibrosis was not associated with survival. Therefore, NAFLD should be assessed in the preoperative setting for predicting long-term prognoses of breast cancer patients Citation Format: Hyunsu Yeoh, Siwon Jang, Jong-Ho Cheun, Jin Ah Kwon, Myoung Seok Lee, Bumjo Oh, In Sil Choi, Sohee Oh, Jongjin Kim, Jeong Hwan Park, Won Kim, Ki-Tae Hwang. Prognostic impact of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis-related liver fibrosis on postoperative long-term outcomes of breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-06.

What Is High-risk Breast Cancer With Pathologically Negative Lymph Nodes for Regional Recurrence?

This study aimed to identify high-risk factors for regional recurrence in patients with breast cancer with pathologically negative lymph nodes. We retrospectively analyzed 3800 patients with stage pT1-pT3 breast cancer and pathologically negative lymph nodes between 2004 and 2012. All patients underwent upfront surgery with curative intent. Adjuvant systemic treatments were administered to most patients (96.7%) based on contemporary guidelines. After a median follow-up of 83 months (range, 7-175 months), the estimated 10-year cumulative incidence rate of regional recurrence was 2.0%. Multivariate competing risk analysis revealed that high histologic grade, positive lymphovascular invasion, and stage pT2-3 were significant risk factors for any regional recurrence. Patients with ≥2 risk factors showed a significantly higher 10-year cumulative incidence rate of any regional recurrence than those with 1 or no risk factors (5.5% vs 1.2%; P < .001). When the number of retrieved lymph nodes was less than 10, the difference in the incidence rate of regional recurrence between patients with ≥2 risk factors and those with 1 or no risk factors was greater (6.6% vs 1.3%, respectively; P < .001). The 10-year disease-free survival was worse in patients with ≥2 risk factors than in those with 1 or no risk factors (84.7% vs 90.0%, respectively; P < .001). Patients with ≥2 risk factors also showed worse 10-year overall survival than did those with 1 or no risk factors (91.3% vs 97.0%, respectively; P < .001). Overall, the cumulative incidence rate of any regional recurrence was low at 10 years. However, patients with ≥2 risk factors showed an increased risk of any regional recurrence and worse disease-free survival, particularly when the number of retrieved lymph nodes was less than 10.

Prognostic value of the 21-gene recurrence score for regional recurrence in patients with estrogen receptor-positive breast cancer.

To evaluate the prognostic value of the 21-gene recurrence score (RS) for regional recurrence (RR) in patients with estrogen receptor-positive breast cancer. We reviewed the medical records of 446 patients who underwent 21-gene RS assay after breast-conserving surgery or mastectomy. The high-RS group was defined as patients who were (1) older than 50years with an RS of 26 or higher, or (2) 50years or younger with an RS of 16 or higher. The 5-year rates of local recurrence (LR), RR, and distant metastasis (DM) were 2.2%, 2.7%, and 4.7%, respectively. The 5-year overall survival (OS) rate was 99.1%. Of the patients, 269 (60.3%) had low-RS, while 177 (39.7%) had high-RS. The 5-year OS rate of the high-RS group was significantly lower than that of the low-RS. The 5-year rates of RR and DM in the high-RS group were significantly higher than those in the low-RS group, while the LR rates did not differ significantly. In multivariable analysis, the high-RS group had a significant relationship with increased RR rate (p = 0.037). Patients who had both high-RS and clinical high-risk features had a significantly higher 5-year RR rate (7.9%) compared with other groups. High-RS was an independent risk factor for RR. The significantly higher RR rate of patients with both high-RS and clinical high-risk features compared with other groups suggests that this patient group can be a potential candidate for regional nodal irradiation.

Technologic (R)Evolution Leads to Detection of More Sentinel Nodes in Patients with Melanoma in the Head and Neck Region.

Sentinel lymph node (SN) biopsy (SNB) has proven to be a valuable tool for staging melanoma patients. Since its introduction in the early 1990s, this procedure has undergone several technologic refinements, including the introduction of SPECT/CT, as well as radioguidance and fluorescence guidance. The purpose of the current study was to evaluate the effect of this technologic evolution on SNB in the head and neck region. The primary endpoint was the false-negative (FN) rate. Secondary endpoints were number of harvested SNs, overall operation time, operation time per harvested SN, and postoperative complications. Methods: A retrospective database was queried for cutaneous head and neck melanoma patients who underwent SNB at The Netherlands Cancer Institute between 1993 and 2016. The implementation of new detection techniques was divided into 4 groups: 1993-2005, with preoperative lymphoscintigraphy and intraoperative use of both a γ-ray detection probe and patent blue (n = 30); 2006-2007, with addition of preoperative road maps based on SPECT/CT (n = 15); 2008-2009, with intraoperative use of a portable γ-camera (n = 40); and 2010-2016, with addition of near-infrared fluorescence guidance (n = 192). Results: In total, 277 patients were included. At least 1 SN was identified in all patients. A tumor-positive SN was found in 59 patients (21.3%): 10 in group 1 (33.3%), 3 in group 2 (20.0%), 6 in group 3 (15.0%), and 40 in group 4 (20.8%). Regional recurrences in patients with tumor-negative SNs resulted in an overall FN rate of 11.9% (group 1, 16.7%; group 2, 0%; group 3, 14.3%; group 4, 11.1%). The number of harvested nodes increased with advancing technologies (P = 0.003), whereas Breslow thickness and operation time per harvested SN decreased (P = 0.003 and P = 0.017, respectively). There was no significant difference in percentage of tumor-positive SNs, overall operation time, and complication rate between the different groups. Conclusion: The use of advanced detection technologies led to a higher number of identified SNs without an increase in overall operation time, possibly indicating an improved surgical efficiency. Operation time per harvested SN decreased; the average FN rate remained 11.9% and was unchanged over 23 y. There was no significant change in postoperative complication rate.

Association of a multiple-step action with cervical lymph node yield of oral cancer patients in an Asian country

BackgroundHigh quality lymph node (LN) yield could increase survival, however strategies to improve LN yield have been seldom reported. This study aimed to assess the multiple-step action to promote quality of neck dissection in oral cancer.MethodsA total of 400 patients with oral cancer who underwent primary tumor resection and neck dissection, including elective and radical neck dissection, were recruited after propensity score matching by clinical T and N categories between January 2009 and September 2018. Patients were treated by two independent departments in our institute. A multiple-step action was initiated in October 2015 in one department, and another department was as a control group. The impact of multiple-step action on LN yield and regional recurrence were analyzed using multivariate analysis and difference-in-differences (DID) linear regression analysis.ResultsThe mean patient age was 55.2 + 11.1 years, and 92% were male. A total of 180 (45%) patients had T3-4 disease, and 129 (32%) patients had N2-3 disease. The multivariate linear regression and DID analyses revealed that multiple-step action had a positive effect on LN yield. A net improvement of LN yield with a coefficient of 13.78 (p < 0.001) after launching multiple-step action (since October 2015) was observed. A borderline protective effect of multiple-step action for cN0 patients with a reduced regional recurrence rate of 11.6% (p = 0.072) through DID analysis was noted.ConclusionsMultiple-step action was associated with increased LN yield and decreased regional recurrence in patients with oral cancer. The observed activity may promote surgeons to improve the quality of neck dissections, is feasible, and could be applied to a widespread patient population.

A Clinical Comparison of the Efficacy of Level I-III Versus Level I-IV Neck Dissection in N0 Early Stage Tongue Squamous Cell Carcinoma

In this study, we compared regional recurrence in patients who had a dissection of levels I-III or levels I-IV. Patients with tongue SCC who were node-negative both clinically and radiologically, and underwent elective supraomohyoid neck dissection (SOHND) or extended supraomohyoid neck dissection (ESOHND) between March 2012, and March 2015 were retrospectively reviewed. The two therapeutic groups were analyzed for the incidence of tumor recurrence and survival. The two groups had statistically similar demographic qualities. Surgery duration and complications were the same in both groups. Complications mainly included internal jugular vein and thoracic duct injury. Tumour size was 46.2% T1, 40.4 % T2, and 13.3% Tx, being statistically similar in both groups. Tumour size had no meaningful correlation with the occurrence of occult neck metastasis in both groups. Local recurrence was more in ESOHND patients, but regional recurrence was similar in both groups. The survival rate was alike in both groups. No significant differences in tumor recurrence and mortality rate were found between patients treated with SOHND versus ESOHND. Thus, SOHND could be considered as a sufficient treatment for early-stage tongue SCC.

Low Risk of Development of a Regional Recurrence After an Unsuccessful Repeat Sentinel Lymph Node Biopsy in Patients with Ipsilateral Breast Tumor Recurrence.

Unlike sentinel lymph node biopsy (SLNB) in the primary setting, the repeat SLNB (rSLNB) in patients with ipsilateral breast tumor recurrence (IBTR) is challenging, because it is difficult to visualize and/or harvest a sentinel lymph node in every patient. Regional treatments options and safety in terms of regional disease control after such an unsuccessful rSLNB remain unclear. This study assesses factors associated with the performance of axillary lymph node dissection (ALND) after unsuccessful rSLNB and evaluates the occurrence of regional recurrences. Data were obtained from the Sentinel Node and Recurrent Breast Cancer (SNARB) study. In 239 patients, the rSLNB was unsuccessful, of whom 60 patients underwent ipsilateral ALND. A shorter time interval between primary treatment and IBTR, and a primary negative SLNB were significantly associated with a higher probability to be treated with ALND after unsuccessful rSLNB (P < 0.001). The 5-year regional-recurrence rate was 0.0% in the ALND group compared with 3.7% in the group treated without ALND (P = 0.113). Of the 179 patients treated without ALND, after a median follow-up of 5.1years (range 0.3-13.2), 7 (3.9%) developed a regional recurrence as first event after unsuccessful rSLNB. None of the seven recurrences occurred in the ipsilateral axilla. Univariable analysis showed no factors associated with regional recurrence as first event after unsuccessful rSLNB (P > 0.05). The present study demonstrates that the risk of regional recurrence in patients with an IBTR and an unsuccessful rSLNB is negligible, irrespective of the use of ALND. This suggests that there is no need for additional treatment of the axilla after an unsuccessful rSLNB.

Outcome Following Radiation Therapy for Locally Advanced Cutaneous Head and Neck Squamous Cell Carcinoma and Analysis of Factors Associated with Recurrence

Radiation therapy is a common treatment modality for skin cancer, either as the primary therapy or as adjuvant treatment in patients with high risk features. However, limited data exist for management of locally advanced head and neck cutaneous squamous cell carcinoma. We report outcome of this unique subset of patients treated with radiation therapy and evaluate prognostic risk factors for recurrences. We retrospectively reviewed the chart of patients with locally advanced cutaneous squamous cell carcinoma who received radiation therapy in our department between January 2001 and December 2017. Patients included in the analysis must have either T3-T4 according to AJCC 8th staging manual or have node positive disease. We excluded patients who had metastatic disease, had tumor outside the head and neck region, or received palliative therapy. We recorded patient (age, sex, immunosuppression status), tumor (primary site, LVI, PNI, T stage, N stage), and treatment (prior surgery, modality, prescription dose, nodal irradiation, concurrent chemotherapy) characteristics. Tumor control and survival rates were calculated using Kaplan-Meier methods and compared using log rank test. We identified 102 patients who met the inclusion criteria. Of the entire cohort, 91 were males and 11 were female. Median age at treatment was 69 (range: 32-94) years old and mean follow up length was 26.8 months. Seventeen patients received concurrent chemotherapy. At the time of analysis, 22 patients had recurred. Five year estimates of local control, regional control, distant control, disease free survival, and overall survival for the entire cohort were 78%, 86%, 91%, 68%, and 57% respectively. The most common pattern of recurrence was local (16 patients), followed by regional nodal recurrences (8 patients), and only 4 patients failed distally. Among those with nodal recurrence, there were slightly more out-of- field (5 patients) than in-field (3 patients) failures. We did not observe any statistical significant differences in term of recurrence and survival rates in regard to T stage, nodal status, elective nodal irradiation for N0 patients, primary tumor site, immunosuppression status, PNI status, or treatment modality (electron versus photon). Patients who had LVI were more likely to experience regional nodal failure at 5 years (36% vs. 12%, p=0.045). In patients with locally advanced head and neck cutaneous squamous cell carcinoma, radiation therapy in conjunction with surgery offers reasonable rates of loco-regional control. We observed a statistical significant higher risk of regional recurrence in patients with LVI. Other risk factors included in our analysis were not shown to correlate with tumor control or survival rates. Ongoing studies seek to identify potential risk factors and patterns of failure following radiation therapy to guide treatment planning.

Role of prophylactic central neck dissection in clinically node-negative differentiated thyroid cancer: assessment of the risk of regional recurrence.

Prophylactic central neck dissection in clinically node-negative patients remains controversial. The aim of this multicenter retrospective study was to determine the rate of metastases in the central neck in clinically node-negative differentiated thyroid cancer patients, to examine the morbidity, and to assess the risk of regional recurrence in patients treated with total thyroidectomy with concomitant bilateral or ipsilateral central neck dissection compared with those undergoing total thyroidectomy alone. 258 consecutive clinically node-negative patients were divided into three groups according to the procedures performed: total thyroidectomy only (group A), total thyroidectomy with concomitant ipsilateral central neck dissection (group B), and total thyroidectomy combined with bilateral central neck dissection (group C). Mean operative time and postoperative stay were shorter in Group A (p<0.01). The incidence of postoperative transient hypoparathyroidism was lower in Group A (p=0.03), whereas no differences in the incidence of permanent hypoparathyroidism and nerve palsy were present. Postoperative radioactive iodine administration was higher in group B and particularly C (p=0.03) compared with group A. There were no statistically significant differences in terms of regional recurrence. Differentiated thyroid cancer has a high rate of central lymph node metastasis even in clinically node-negative patients; in the present study there was no statistically significant difference in the rates of locoregional recurrence between the three modalities of treatment. Total thyroidectomy appears to be an adequate treatment for clinically node-negative differentiated thyroid cancer. Prophylactic central neck dissection might be considered for differentiated thyroid cancer patients with large tumor size or extrathyroidal extension.

Immunohistochemical analysis of EGFR and hyaluronan in tongue cancer and the development of regional recurrence in patients initially diagnosed N0

Objective: To investigate whether the extent of expression of hyaluronan (HA) and epidermal growth factor receptor (EGFR) in squamous cell carcinoma of the mobile tongue can predict the risk of cervical metastasis and survival.Study design: Retrospective histopathologic study.Methods: Surgical specimens from 64 patients who had undergone surgery for squamous cell carcinoma of the mobile tongue were assessed using immunohistochemistry to investigate the expression of HA and EGFR in the primary tumours, and the data were then correlated to cervical metastasis and survival.Results: There was a significant correlation between the intensity of HA staining and patient survival (p .024), and a weak correlation between the staining proportion of EGFR and the risk for regional recurrence (AUC 66).Conclusions: This study indicates that immunoscoring using HA could be used to provide prognostic tools for tongue cancer, and that it might be of interest to study the prognostic properties of EGFR further concerning the risk for regional recurrence after the primary treatment.

Postoperative (Chemo)Radiotherapy for Oral Cavity Squamous Cell Carcinomas: Outcomes and Patterns of Failure

AimsTo determine outcomes after adjuvant radiotherapy for squamous cell carcinoma of the oral cavity and to correlate locoregional recurrence patterns with radiotherapy target volumes. Materials and methodsAll patients receiving adjuvant radiotherapy±chemotherapy after surgery with curative intent for oral cavity squamous cell carcinoma between 2007 and 2012 were retrospectively analysed. Locoregional recurrences were reconstructed on the planning computed tomography scan by both deformable image co-registration and by visual assessment. Recurrences were categorised as in-field, marginal or out-of-field if >95%, 20–95%, and <20% of the recurrence volume was encompassed by 95% of the prescription isodose, respectively. ResultsIn total, 106 patients with a median follow-up of 42 months were included. Oral cavity subsites included oral tongue (54%) and floor of mouth (32%). Thirty (28%) patients received concurrent chemotherapy. Fifty-five (52%) patients received bilateral neck radiotherapy. Two year overall, disease-free, local disease-free, regional disease-free and distant metastases-free survival were 72, 83, 92, 89, 94%, respectively. On multivariate analysis, extracapsular nodal spread was the only factor significantly associated with inferior overall survival. Fourteen (13%) patients have experienced locoregional failure. Of the eight local recurrences at the primary tumour site, four, three and one were classified as in-field, marginal and out-of-field, respectively. Of 10 regional recurrences, one, one and eight were in-field, marginal and out-of-field. There were 7/21 (33%) contralateral regional recurrences in patients with pN2a/b disease who did not receive contralateral neck irradiation; there were 0/21 (0%) and 0/9 (0%) contralateral regional recurrences in patients with pN0 or pN1 disease, respectively, who did not receive contralateral neck irradiation. ConclusionMarginal recurrences highlight the need for generous target volume delineation. Based upon rates of contralateral regional recurrences, a comprehensive approach to target volume selection should be advised for tumour subsites with bilateral lymphatic drainage in the presence of pN2a/b disease.

Patterns and treatment of neck metastases in patients with salivary gland cancers.

Management of the neck in patients with salivary gland cancer is controversial. This study aimed to identify clinicopathologic characteristics associated with regional metastases and regional recurrence in patients with salivary gland carcinoma. Of 363 study patients, 51 underwent therapeutic neck dissection (TND) and 312 underwent either elective neck dissection (END, n = 110) or no neck dissection (NoND, n = 202). Univariate and multivariate analyses were performed to identify clinicopathologic characteristics associated with regional metastases and recurrence. Pathologic neck metastases were identified in 17/110 (15.5%) END patients and neck recurrence was identified in 5/202 (2.5%) NoND patients. Histologic grade (P < 0.001), tumor site (P = 0.008), and lymphovascular invasion (P < 0.001) were independent risk factors for neck metastases. Nodal metastases were more common in high-grade tumors (P < 0.001), at levels I-III in END patients and levels I-V in TND patients. Multivariate analyses identified histologic grade (P = 0.020), clinical N2 classification (P = 0.007), and extranodal extension (P = 0.005) as independent factors for regional recurrence after treatment. Patients with high-grade cancers should receive END involving levels I-III, whereas patients with node-positive salivary cancers should receive comprehensive TND involving all levels (I-V).

Abstract 2867: EGFR expression in T1/T2 oral tongue and floor of the mouth carcinoma

Abstract Epidermal growth factor receptor (EGFR) is a molecular maker that regulates the cell growth and plays an important role in tumor proliferation, invasion and metastasis formation. Objective: In this study we examined the association of immunohistochemical expression of EGFR with clinicopathological parameters, lymph node metastasis, regional recurrence and survival in selected cases of early squamous cell carcinoma (SCC) of the oral tongue and floor of the mouth. Methods: Patients with early stage SCC of oral tongue and floor of the mouth were treated surgically at a single institution from 1980 to 2010. Specimens from 139 patients were analyzed for EGFR expression using monoclonal antibody. Results: This study included 139 patients, 96 men (69%), with ages ranging from 21 to 85 years old (mean, 58 years). The tumor site was the tongue in 105 cases (75.5%) and the floor of the mouth in 34 (24.5%). With regard to pathological T-stage, 69 cases were pT1 (52.7%) and 62 were pT2 (47.3%). EGFR was overexpressed in 18 cases (13%) and was significantly associated with pT (p=0.017), thickness greater than 4mm (p=0.017), muscular invasion (p=0.014), desmoplastic reaction (p=0.021), inflammatory infiltrate (p=0.029), lymphatic embolization (p=0.016), mode of invasion (p=0.027) and perineural invasion (p=0.007). The overexpression of EGFR was also associated with lymph node metastasis (p=0.038) and regional recurrence (p=0.014). The cancer-specific survival in 5 years decreased from 90% in the group without EGFR expression to 75.3% in the EGFR overexpression group (p=0.019). Conclusion: The EGFR overexpression was associated with more aggressive pathological features, lymph node metastasis and regional recurrence in patients with early oral tongue and floor of the mouth squamous cell carcinoma. Citation Format: Natalie Kelner, Clovis Antonio Lopes Pinto, Luiz Paulo Kowalski, Claudia Malheiros Coutinho-Camillo. EGFR expression in T1/T2 oral tongue and floor of the mouth carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2867. doi:10.1158/1538-7445.AM2014-2867

Lymphoscintigraphy in Oral Squamous Cell Carcinoma Sentinel Node Biopsy and Its Role in the Surgical Planning

The purpose of this study was to analyze the influence of different lymphatic pathways on surgical planning and the reliability of sentinel lymph node (SLN) biopsy to predict regional recurrence in patients with clinically N0 oral squamous cell carcinoma (OSCC). Twenty-five patients with cT1/T2 N0 OSCC underwent a lymphoscintigraphy and an SLN biopsy. Elective neck dissection was performed at the validation stage and in patients with metastatic SLN. Scintigraphic and surgical SLN detection, pathologic status of SLN and of elective neck dissection, and regional recurrence in patients with negative SLN (pN0(sn)) were all analyzed. Scintigraphic and surgical detection were 96% and 100%, respectively, with 68% of negative SLN. Lymphoscintigraphy modified surgery in 32% of patients. In pN0(sn) patients, the free-of-disease survival rate was 88%. These results support the reliability of sentinel node biopsy in OSCC. Presurgical lymphoscintigraphy is essential, because it can modify the surgical procedure.

Abstract P3-14-12: Risk factors for local regional recurrence in patients undergoing breast conserving surgery following neoadjuvant chemotherapy and validation of the MD Anderson prognostic index

Abstract Background: Breast conserving surgery (BCS) is a primary goal of neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer, especially with recent improvements in tumor response. Patient selection for BCS following NAC may be different than classic local regional recurrence (LRR) risk factors. Here we investigate risk factors for LRR and attempt to validate the MD Anderson Prognostic Index (MDAPI) for LRR in a single institution series. Methods: Data were analyzed for 178 consecutive patients treated at one institution who underwent NAC followed by BCS and whole breast radiotherapy between the years 1999 and 2011. Using univariate and multivariate analysis, multiple clinicopathologic factors were investigated, as well as the subgroups of the MDAPI. Chi-square tests were used to compare the LRR-free survival rates between subgroups. Results: The median follow-up was 70.33 months and the 5-year LRR-free survival was 93.18%. Multivariate analysis demonstrated that clinical stage and pathologic stage were both statistically significant for LRR-free survival, while pattern of residual disease was of borderline statistical significance. The MDAPI was not significantly associated with LRR-free survival (MDAPI low 93.80%, Intermediate 88.23%, High 88.89%). Five-Year Local Regional Recurrence -Free Survival According to Clinicopathologic Factors # Patients5yr LRR-Free SurvivalPathologic Stage p = 0.03301580.0%14292.5%27692.5%3994.6%pCR38100%Clinical Stage p = 0.0291580.0%213796.3%33883.8%MDAPI Score P = 0.506Low (0 or 1)12993.80%Int (2)3488.23%High (3)988.89%*MDAPI Score Factors cN Stage P = 0.305cN0-N116593.3%cN2-N31070%LVI P = 0.453No-LVI15793.5%Yes-LVI2390.9%pT&amp;gt;2cm P = 0.158Residual Tumor Morphology P = 0.055Multifocal Resid Tumor5996.5%Solitary Mass6690.6%No Resid Tumor5394.3%*These factors make up the MDA Prognostic Index Conclusion: Overall the 5-year LRR-free survival was high at 93.18%, which compares favorably to similar neoadjuvant patient cohorts who receive mastectomy instead of BCS. Our analysis indicates clinical stage and pathologic stage are significant in predicting LRR. Of the four predictive factors utilized by the MDAPI, only multifocal residual disease showed weak predictive power (p = 0.055) in our population; however, it correlated with higher LRR-free survival, the opposite of its indication in the MDAPI. The MDAPI was not useful in our patient population; the risk groups did not significantly correlate with LRR-free survival. This may be secondary to low total number of recurrence events and also the small number of patients in the MDAPI-high group (9 patients had an MDAPI score of 3, and none had a score of 4). As further data emerge regarding biology of tumors and recurrence, it may be a combination of molecular profiling and residual cancer burden that is a better predictor for LRR. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-12.

Models predicting non-sentinel node involvement also predict for regional recurrence in breast cancer patients without axillary treatment

Non-SN prediction models are frequently used in clinical decision making to identify patients that may not need axillary treatment, but these models still need to be validated by follow-up data. Our purpose was the validation of non-sentinel node (SN) prediction models in predicting regional recurrences in patients without axillary treatment. We followed a cohort of 486 women with favorable primary tumor characteristics and pN0(i+)(sn) or pN1mi(sn) for median 4.5 years. None of the patients underwent axillary treatment. Based on four published non-SN prediction models, the threshold allowing separation into low versus high-risk on non-SN involvement was set at 10%. Overall 5-year regional recurrence rate was 3.0% (SE, ±0.1%). Using the Tenon scoring system, 438 low-risk patients had a 5-year regional recurrence rate of 2.3% (±0.8%), and 48 high-risk patients a recurrence rate of 10.1% (±0.4%). The MSKCC nomogram identified 300 low-risk patients with a recurrence rate of 2.8% (±1.1%), versus 166 high-risk patients with a rate of 3.4% (±0.5%) (20 patients not assessable). The Stanford nomogram identified 21 high-risk patients without recurrence, and 465 low-risk patients with a 3.2% (±0.9%) recurrence rate. A Dutch model discriminated between 384 low-risk patients with a recurrence rate of 2.2% (±0.8%) and 102 high-risk patients with a rate of 6.3% (±2.9%). The Tenon scoring system outperformed the other models as it identified the largest subgroup of patients with low recurrence rate. In patients resembling our cohort we would recommend axillary treatment if they had a Tenon score above 3.5.

Predictors of regional recurrences in breast cancer patients with negative sentinel node.

51 Background: For patients with clinically node-negative, early-stage breast cancer, sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) as a standard method for staging of regional lymph nodes. Regional recurrences after negative (SLNB) have generally been reported in the range of 0.5 to 2% and factors associated with regional recurrence in patients with negative SLNB are still to be elucidated. In this study, we evaluated regional recurrence rates and predictors of regional recurrences in patients with negative SLNB. Methods: Between January 2001 and December 2012, 1,322 patients with clinical node-negative invasive breast cancer less than 3cm underwent SLNB at Keio University Hospital. Of 1,322 patients with SLNB, 1,033 patients with negative SLNs were included in this study. Sentinel lymph nodes (SLNs) were detected using a combined method of blue dye and small-sized technetium-99m-labeled tin colloid. Intraoperative frozen examination was performed with hematoxylin and eosin (HE) staining. SLNs, fixed and embedded in paraffin, were additionally diagnosed with HE staining and immunohistochemical analysis. Results: Median age was 57.0 years (range, 25-89) and median tumor size was 1.9cm (range, 0.5-6.0cm). After a median follow-up of 54.8 months, there were 13 regional (1.3%) and 26 distant recurrences (2.5%). Median disease-free interval of regional and distant recurrences was 32.6 and 22.7 months, respectively (p=0.761). Higher nuclear grade (NG) was significantly correlated with regional and distant recurrences (p=0.001 and p=0.008). The rate of lymphovascular invasion (LVI) was significantly higher in patients with regional recurrences comparing with patients without recurrences (58.3% vs. 27.6%, p=0.026), however LVI was not a significant predictor of distant recurrences (p=0.072). Estrogen receptor negativity was significantly correlated with distant recurrences (p=0.013), whereas it was not associated with regional recurrences (p=0.626). Conclusions: Regional recurrences were rare in early-stage breast cancer patients with negative SLNB. LVI and NG can be used as predictive factors of regional recurrences after negative SLNB.

Risk factors for local and regional recurrence in patients with resected N0–N1 non-small-cell lung cancer, with implications for patient selection for adjuvant radiation therapy

The purpose of this study was to evaluate the actuarial risk of local and regional failure in patients with completely resected non-small-cell lung cancer (NSCLC), and to assess surgical and pathological factors affecting this risk. Between January 1998 and December 2009, 1402 consecutive stage I-III (N0-N1) NSCLC patients underwent complete resection without adjuvant radiation therapy. The median follow-up was 42 months. Local-regional recurrence was identified in 9% of patients, with local failure alone in 3% of patients, regional failure alone in 4% of patients, and both local and regional failure simultaneously in 2% of patients. Patients who had local failure were found to be at increased risk of mortality. By multivariate analyses, three variables were shown to be independently significant risk factors for local [surgical procedure (single/multiple wedges+segmentectomy versus lobectomy+bilobectomy+pneumonectomy), tumor size>2.7 cm, and visceral pleural invasion] and regional (pathologic N1 stage, visceral pleural invasion, and lymphovascular space invasion, LVI) recurrence, respectively. Patients with N0-N1 disease have low rates of locoregional recurrence after surgical resection. However, several prognostic factors can be identified that increase this risk and identify patients who may benefit from adjuvant treatment.

Sebaceous gland carcinoma of the head and neck: The Princess Margaret Hospital experience

The purpose of this study was to identify prognostic factors predicting outcomes in sebaceous gland carcinomas. We conducted a retrospective medical chart review of patients with sebaceous carcinomas of periorbital (n = 33) and extraorbital sites (n = 13). Patients with periorbital tumors had higher recurrence rates than did patients with extraorbital tumors (64% vs 23%; p = .032). Patients who were older than 60 years (p = .035) and had lower eyelid tumors (p < .0001) had a lower disease-free survival rate than did patients with upper eyelid tumors. Patients with sebaceous carcinomas had a high rate (60%) of occult lymph node metastases. Periorbital tumors are associated with poorer outcomes than are extraorbital tumors. Lower eyelid carcinomas have the worst prognosis and should be treated more aggressively. Our findings of a high incidence of occult neck disease and a high rate of regional recurrence in patients with sebaceous carcinomas support the consideration of prophylactic elective neck dissections for treating such patients.

Regional Recurrence in Breast Cancer Patients With Sentinel Node Micrometastases and Isolated Tumor Cells

The impact of axillary treatment in daily practice on 5-year regional recurrence rate in breast cancer patients with isolated tumor cells or micrometastases in the sentinel node (SLN). Axillary dissection is recommended in patients with tumor-positive SLNs. But, in recent studies, regional recurrence rates seemed low if dissection was omitted. We identified all patients in The Netherlands with invasive breast cancer who had an SLN biopsy before 2006, favorable primary tumor characteristics, and node-negative disease, isolated tumor cells or micrometastases as final nodal status. The primary endpoint was regional recurrence rate. To investigate differences in recurrence rates between patients with and without axillary treatment, a proportional hazard regression was carried out correcting for potential confounders. In total, 857 patients with node-negative disease, 795 patients with isolated tumor cells, and 1028 patients with micrometastases in the SLN were included. Without axillary treatment, the 5-year regional recurrence rates were 2.3%, 2.0%, and 5.6%, respectively. Compared with patients who underwent axillary treatment, the adjusted hazard ratio for regional recurrence in patients who underwent an SLN procedure only was 1.08 (95% CI, 0.23-4.98) for node-negative disease, 2.39 (95% CI, 0.67-8.48) for isolated tumor cells, and 4.39 (95% CI, 1.46-13.24) for micrometastases. Doubling of tumor size, grade 3 and negative hormone receptor status were also significantly associated with recurrence. Not performing axillary treatment in patients with SLN micrometastases is associated with an increased 5-year regional recurrence rate. Axillary treatment is recommended in patients with SLN micrometastases and unfavorable tumor characteristics.