Risk Factors For Locoregional Recurrence Research Articles

Comparison of unilateral versus bilateral central neck dissection for clinically invasive papillary thyroid carcinoma.

The American Thyroid Association guidelines primarily recommend central neck dissection for papillary thyroid carcinoma with advanced primary tumors or clinically positive neck nodes. However, the appropriate extent of dissection remains unclear. We aimed to compare the rate of locoregional recurrence between unilateral and bilateral central neck dissection in invasive papillary thyroid carcinoma. Among 330 consecutive patients who underwent total thyroidectomy with central neck dissection for advanced papillary thyroid carcinoma, 212 underwent unilateral central neck dissection (UCND group) while 118 underwent bilateral central neck dissection (BCND group). We performed 1:1 propensity score matching, resulting in 99 matched pairs. Surgical outcomes and safety were compared between the two groups. Additionally, the impact of surgery on locoregional recurrence was compared using survival analysis. During a follow-up of 47.8 ± 20.4 months, 29 (8.8%) patients experienced locoregional recurrence within the entire study cohort. Following propensity score matching, no significant difference in recurrence-free survival was observed between the two groups (log-rank p = 0.516). Multivariate analysis revealed that only T4 staging was an independent risk factor for locoregional recurrence (p = 0.006). The mean number of total and metastatic central lymph nodes retrieved were significantly greater in BCND group (14.1 vs. 9.3, p < 0.001 and 6.8 vs. 4.6, p = 0.005, respectively). There was no significant difference in postoperative stimulated thyroglobulin levels between the two groups (0.79 ng/mL vs. 1.44 ng/mL, p = 0.389). The present study demonstrates no prognostic benefit in conducting bilateral central neck dissection. Unilateral central neck dissection may be the preferred choice for clinically invasive papillary thyroid carcinoma.

Risk Factors for Locoregional Recurrence Following Mastectomy for Localized Breast Cancer in a Nigerian Teaching Hospital

Background: Mastectomy is an integral part of the management of breast cancer, especially in resource-limited centers. This study aimed to describe the outcomes in terms of locoregional recurrence (LRR) and distant metastasis (DM) after modified radical mastectomy (MRM) for breast cancer and factors associated with them. Methods: This was a retrospective study of patients who underwent mastectomy between October 2012 and September 2017. Data generated were analyzed using SPSS version 23.0. The results were presented using descriptive statistics. Inferential statistics was done using the chi-square test with statistical significance set at p &lt;0.05. Results: Sixty-three (88.7%) of 71 patients who had MRM over the study period were eligible. Their ages ranged from 24-80 years with a median of 49 years (IQR, 43-59years). Lump size ranged from 2-18 cm (mean, 7.8±3.5 cm) and the lump duration was 1-48 months (median 6.0, IQR, 4.0-10.0 months). Sixteen (25.4%) patients developed LRR. The interval to occurrence of LRR after mastectomy ranged from 4-36 months (median, 9 months, IQR, 6.0-20.0). Eighteen (28.6%) patients developed distant metastasis 9-60 months after surgery (median 19, IQR 12.0-37.0 months) and 50% of those with LRR were among. Metastasis mostly affected the lungs and pleura in 55.6%. Mean tumour size ≥10cm (p &lt;0.000), mean lump duration &gt;11months, advanced disease T3/4 (p=0.01) and higher number of positive lymph nodes (p=0.011) were significantly associated with LRR. Both tumour size (p=0.01) and positive lymph nodes (p=0.015) are predictors of LRR. Conclusion: LRR and metastasis are common occurrences after mastectomy. Early presentation and availability of more adjuvant therapies can reduce the rate.

Risk Factors for Locoregional Recurrence Following Mastectomy for Localized Breast Cancer in a Nigerian Teaching Hospital

Background: Mastectomy is an integral part of the management of breast cancer, especially in resource-limited centers. This study aimed to describe the outcomes in terms of locoregional recurrence (LRR) and distant metastasis (DM) after modified radical mastectomy (MRM) for breast cancer and factors associated with them. Methods: This was a retrospective study of patients who underwent mastectomy between October 2012 and September 2017. Data generated were analyzed using SPSS version 23.0. The results were presented using descriptive statistics. Inferential statistics was done using the chi-square test with statistical significance set at p &lt;0.05. Results: Sixty-three (88.7%) of 71 patients who had MRM over the study period were eligible. Their ages ranged from 24-80 years with a median of 49 years (IQR, 43-59years). Lump size ranged from 2-18 cm (mean, 7.8±3.5 cm) and the lump duration was 1-48 months (median 6.0, IQR, 4.0-10.0 months). Sixteen (25.4%) patients developed LRR. The interval to occurrence of LRR after mastectomy ranged from 4-36 months (median, 9 months, IQR, 6.0-20.0). Eighteen (28.6%) patients developed distant metastasis 9-60 months after surgery (median 19, IQR 12.0-37.0 months) and 50% of those with LRR were among. Metastasis mostly affected the lungs and pleura in 55.6%. Mean tumour size ≥10cm (p &lt;0.000), mean lump duration &gt;11months, advanced disease T3/4 (p=0.01) and higher number of positive lymph nodes (p=0.011) were significantly associated with LRR. Both tumour size (p=0.01) and positive lymph nodes (p=0.015) are predictors of LRR. Conclusion: LRR and metastasis are common occurrences after mastectomy. Early presentation and availability of more adjuvant therapies can reduce the rate.

Assessment of Postmastectomy Radiation Therapy Receipt by Age and Association With Outcomes in Women With Breast Cancer

PurposePostmastectomy radiation therapy (PMRT) reduces locoregional recurrence (LRR) and improves overall survival (OS) in patients with breast cancer. Young age has been recognized as a risk factor for LRR. The primary objective of this study was to determine if recommendations for PMRT differed among patients younger than 50 years as compared to women aged 50 years or older. MethodsWe reviewed medical records of patients with breast cancer who underwent mastectomy with or without PMRT from 2010 through 2018. Univariable and multivariable models were used to estimate the association of age with PMRT. ResultsOf 2471 patients, 839 (34%) were <50 years; 1632 (66%) were ≥50 years. Patients <50 years had a higher percentage of grade 3 tumors, hormone receptor (HR) negative and/or Her-2/neu positive tumors, clinical stage T2/T3 tumors, and nodal involvement. Compared with patients ≥50 years, patients <50 years were more likely to undergo PMRT (OR 1.57; P = .001) and regional node irradiation (RNI) to the internal mammary nodes. Advanced clinical and pathologic stage, invasive tumor histology, the presence of lymphovascular invasion, and treatment with systemic chemotherapy were predictors of PMRT receipt for patients <50 years (P < .05). PMRT was associated with improved OS and recurrence free survival (RFS) among all patients (P < .01). ConclusionPatients <50 years were more likely to undergo PMRT and to receive RNI to the internal mammary nodes but were also more likely to have other risk factors for recurrence that would warrant a PMRT recommendation. PMRT improved OS and RFS for all patients.

Risk Factors for Locoregional Recurrence and Distant Metastasis in 143 Patients with Adenoid Cystic Carcinoma of the External Auditory Canal

AimsAdenoid cystic carcinoma (ACC) grows slowly and is characterised by potential recurrence and metastasis to distant organs. This study aimed to evaluate the risk factors for locoregional recurrence (LRR) and distant metastasis in patients with ACC of the external auditory canal (EAC). Materials and methodsDemographic, pathological, therapeutic and survival data of 143 patients with EAC ACC were reviewed in this study. Univariate and multivariate Cox proportional hazard regression analyses were carried out to determine the risk factors for LRR and distant metastasis. Factors associated with overall survival after LRR and distant metastasis were also analysed. ResultsDuring a median follow-up of 49 months, 31 of 143 patients were observed with LRR and 34 developed distant metastasis. Bone invasion and histological subtype were independent risk factors for locoregional recurrence-free survival. T stage and LRR were independent risk factors for distant metastasis-free survival. Salvage surgery and adjuvant radiotherapy or chemoradiotherapy for LRR resulted in better survival, whereas extrapulmonary metastasis and LRR were associated with a higher risk of poor survival after distant metastasis. ConclusionPatients with distant metastases, especially those with LRR, are at significant risk of poor prognosis. Our findings emphasise the importance of long-term regular follow-up and recommend surgical intervention with radiotherapy for recurrent EAC ACC.

Impact of dysplasia at resection margin on oncologic outcome after curative resection of oral tongue squamous cell carcinoma: significance of high-grade dysplastic resection margin.

This study aimed to compare the oncologic outcomes among negative, close, positive, and dysplasia resection margins (RMs) with oral tongue squamous cell carcinoma (OSCC) and to investigate the impact of dysplastic RMs. The 565 patients were retrospectively analyzed and divided into four groups according to RM. Dysplasia was classified into mild, moderate, and severe subgroups. RMs consisted of negative (62.1%), close (27.1%), positive (2.1%), and dysplastic (8.7%). In multivariate analysis, advanced T/N stages and positive RM were significant risk factors for overall survival, while dysplasia at the RM was not a significant risk factor for locoregional recurrence or overall survival. In subgroup analysis of patients with dysplastic margin, RM with severe dysplasia showed higher recurrence than mild and moderate dysplasia. Dysplastic RM was not a risk factor for recurrence and survival. Severe dysplasia RM should be carefully observed due to higher recurrence compared to other dysplasia RMs.

Close distal margin is associated with locoregional rectal cancer recurrence: A multicenter study.

The importance of the radial margin for rectal cancer resection is well understood. However, surgeons have deemphasized the distal margin, accepting very close distal margins to perform sphincter-preserving surgery. We hypothesized that distal margins < 1 cm would be an independent risk factor for locoregional recurrence. The objective was to determine whether close distal margins are associated with increased locoregional recurrence risk. This was a multi-institutional retrospective cohort study conducted at six academic medical centers including patients who received low anterior resection surgery for primary rectal cancer between 2007 and 2018. Of 556 low anterior resection patients, the rate of close distal margin was 12.8% (n = 71), and the locoregional recurrence rate was 5.0% (n = 28). The locoregional recurrence rate for close distal margin cases was 9.9% (n = 7) compared to 4.3% (n = 21) for distal margins ≥1.0 cm. In multivariable analysis, the only factor significantly associated with locoregional recurrence was close distal margin (adjusted odds ratio: 2.80, confidence interval: 1.08-7.25, p = 0.035). Rectal cancer patients with close distal margins (<1 cm) following low anterior resection had a significantly higher risk for locoregional recurrence. Therefore, the decision to perform low anterior resection with margins < 1 cm should be taken with caution.

Molecular risk factors for locoregional recurrence in resected non-small cell lung cancer.

Locoregional recurrence is of high risk and is associated with a poor prognosis in terms of OS for non-small cell lung cancer (NSCLC). Local control is essential for radical cure of NSCLC. Previous studies have investigated the clinicopathological risk factors for locoregional recurrence, but the genomic biomarkers associated with locoregional recurrence have been inadequately studied. A total of 118 patients who underwent tumor resection with mutation-detected tumor specimens were included. Tumor samples at surgery and pretreatment/postoperative blood samples were collected for mutational profiling. Among 48 patients with disease recurrence, 46% developed locoregional recurrence (LR) and 75% developed distant metastasis (DM). The 3-year actuarial risk of LR and DM was 25% and 43%, respectively. The first sites of failure were locoregional only (29%), locoregional and distant (10%), and distant only (61%). Patients with LR showed significantly higher ctDNA level than those with only DM at the time of initial recurrence. On multivariate analysis of baseline risk factors, the presence of allele frequency heterogeneity and baseline ctDNA shedding were found to be independently associated with a higher risk of LR. Patients with disruptive TP53 mutations had significantly lower LR-free survival as compared to patients with wild-type TP53 or nondisruptive mutations. EGFR mutations showed a favorable prognostic value for LR and is not induced by EGFR tyrosine kinase inhibitor therapy. Both disruptive TP53 mutation and EGFR mutation remained the significant prognostic factor after adjustment for histological type, pathologic nodal stage and adjuvant therapy. Nearly half of disease recurrences after surgery for NSCC involved locoregional sites. We identified genomic biomarkers from baseline tumor and ctDNA samples which showed promising prognostic value for LR only. This can help identify patients who had a higher risk of locoregional recurrence regardless of the risk of distant metastasis.

Meta-Analysis of Rates and Risk Factors for Local Recurrence in Surgically Resected Patients With NSCLC and Differences Between Asian and Non-Asian Populations

IntroductionPostoperative radiotherapy (PORT) reduces local failure in patients with NSCLC, without a clear overall survival benefit. It is unknown whether the subsets of patients benefit. Two recent large randomized controlled trials, PORT-C (People’s Republic of China) and Lung ART (Europe), reported widely different locoregional recurrence (LR) rates in the control arms, at 18.3% and 28.1% (46% of which were mediastinal recurrences), respectively. We performed a meta-analysis of patients with pathologic (p) N0 to N2 disease to evaluate the risk factors for LR and to explore possible differences in recurrence risk between Asian population (AP) and non-Asian population (NAP). MethodsWe identified all original studies of curative NSCLC surgical resection which reported risk of LR between January 1, 2000, and January 10, 2021, excluding studies with less than 10 LR, patients with metastatic disease, or any neoadjuvant therapy. A total of 87 studies were identified with pN0 to N2 disease; of these, 56 were of high quality (HQ) on the basis of the Newcastle-Ottawa Scale. For each risk factor, we derived pooled relative risk (RR) and 5-year rate estimates using random-effects models. ResultsOverall, the three significant highest pooled RRs (95% confidence intervals) for LR were pN2 versus pN0 (3.01, 1.39–6.55), lymphovascular invasion (1.92, 1.58–2.33), and advanced pT3–4 stage versus pT1 (1.86, 1.53–2.25). For HQ studies, the highest RRs for LR were lymphovascular invasion (1.94, 1.57–2.40), sublobar versus lobar resection (1.86, 1.46–2.36), and pN1 versus pN0 (1.84, 1.37–2.47), but pN2 versus pN0 was no longer significant (3.0, 0.57–15.61), on the basis of only two eligible studies. The RRs for LR were consistent for most factors in AP and NAP, although the RR for male versus female sex was higher in AP (1.44, 1.21–1.72) than in NAP (1.09, 0.99–1.19). Where reported, the pooled rate of LR at 5 years was lower in AP (12.0%) than in NAP (22.7%), despite similar overall 5-year recurrence rates (both LR and distal) in both populations: 38.0% in AP and 37.3% in NAP. Nevertheless, a lower 5-year mortality rate was noted in AP (24.3%) than in NAP (45.9%). ConclusionsThere is little high-quality evidence to support the hypothesis that pN2 disease is a risk factor for LR, but LR seems to be lower in Asians. Prospective evaluation of LR factors and rates may be necessary before further prospective evaluation of PORT, because it may not depend on nodal status alone. Recurrence rates may differ in Asians. The impact of mutational status and modern treatment including targeted therapies and immune checkpoint inhibitors is inadequately studied.

Abstract 1327: Mechanism of tumor microenvironment remodeling and progression based on FAM20C-mediated extracellular kinome network in oral squamous cell carcinoma

Abstract Tumorigenesis and tumor growth are accomplished through the crosstalk between intra- and extracellular molecules, which is often mediated by phosphorylation, and research on intracellular signal transduction has made great progress. Despite the significance of the tumor microenvironment (TME) for tumor progression, relatively few kinome studies have been conducted on phosphorylation cascade in the TME of oral squamous cell carcinoma (OSCC). OSCC is an aggressive cancer with a high recurrence rate of 40-60%, but there are uncertain molecular classification and no identifiable driver mutation genes to be a druggable target. As the presence of extranodal extension (ENE) is currently the most significant risk factor for locoregional recurrence or distant metastasis, differences in molecular profiles between patients with and without ENE may provide insight into regulatory mechanisms that are critical for the recurrence and progression of OSCC. Using LC-MS-based secretome analysis, we examined total and phosphoproteins from ten patients' plasma with or without ENE. Global proteome analysis revealed that the ENE group had higher levels of protein phosphorylation, the ERK 1/2 cascade, signal transduction, phagocytosis, and the integrin-mediated signaling pathway than the without ENE group. Furthermore, 319 phosphosites originating from 165 proteins were discovered, with the majority of phosphorylated proteins having lipid binding, complement system, extracellular matrix, and calcium binding. Interestingly, we discovered 82 proteins with Ser-x-Glu/pSer sites among the phosphorylated proteins, indicating that they could be substrates of the unique extracellular secreted serine kinase, family with sequence similarity 20C (FAM20C). Proteins associated to tumor metastasis, such as insulin-like growth factor-binding proteins (IGFBPs), osteopontin (OPN), and serine protease inhibitors (Serpins), are known as substrates for the FAM20C. In accordance with the proteome results in plasma, gene ontology (GO) term analysis using the NanoString oncology panel revealed that extracellular structure organization-related genes were up-regulated and enzyme inhibitor, kinase regulator, and protein tyrosine kinase activity-related genes were down-regulated in human OSCC cell line, Cal-27, with knockout of FAM20C. Furthermore, we functionally demonstrated that FAM20C depletion inhibited invasion by lowering protein production of Vimentin, TGF-β, and ERK phosphorylation. Collectively, we discovered that the secreted kinase FAM20C controls metastasis by cross-talking with proteins in the TME and propose that this may be the evidence for OSCC prognosis. (This research was supported by National Cancer Center, Korea (No. 2210980) and National Research Foundation of Korea grant funded by the Korea government (No. 2020M3A9A5036362)). Citation Format: Mi Rim Lee, Yu-Sun Lee, Sumin Kang, Hye Won Shon, Jeong Eun Gong, Hye Joo Park, Jung-Ah Hwang, Kyung-Hee Kim, Sung Weon Choi, Yun-Hee Kim. Mechanism of tumor microenvironment remodeling and progression based on FAM20C-mediated extracellular kinome network in oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1327.

Comparative Survival Function in Patients with Positive Surgical Margins Following Laryngectomy.

Aims: This study aims to make a comparative analysis of disease-free survival (DFS) and overall disease-specific survival (OS) in patients with laryngeal carcinoma. Materials and methods: The study was designed retrospectively. Sixteen patients with postoperative PSM and 30 with negative surgical margins (NSM) were included. Survival analysis and Long-Rank comparisons was performed for DFS and OS between groups. Results: PSM was a significant independent risk factor for loco-regional recurrence and disease-related mortality (p = 0.004, HR: 1.6, p = 0.002, HR: 3.2, respectively). DFS and OS were significantly longer in NSM group (p = 0.001 and 0.003, respectively). For PSM group, 2- and 5-year DFS rates were 57%; OS rates were 80% and 34% respectively. In NSM group, 2- and 5-year DFS rates were 96% and 83%; OS rates were found to be 96%. Conclusion: PSM had significant relation with poor prognosis.

Diagnosis of cervical lymph node metastasis with thyroid carcinoma by deep learning application to CT images.

The incidence of thyroid diseases has increased in recent years, and cervical lymph node metastasis (LNM) is considered an important risk factor for locoregional recurrence. This study aims to develop a deep learning-based computer-aided diagnosis (CAD) method to diagnose cervical LNM with thyroid carcinoma on computed tomography (CT) images. A new deep learning framework guided by the analysis of CT data for automated detection and classification of LNs on CT images is proposed. The presented CAD system consists of two stages. First, an improved region-based detection network is designed to learn pyramidal features for detecting small nodes at different feature scales. The region proposals are constrained by the prior knowledge of the size and shape distributions of real nodes. Then, a residual network with an attention module is proposed to perform the classification of LNs. The attention module helps to classify LNs in the fine-grained domain, improving the whole classification network performance. A total of 574 axial CT images (including 676 lymph nodes: 103 benign and 573 malignant lymph nodes) were retrieved from 196 patients who underwent CT for surgical planning. For detection, the data set was randomly subdivided into a training set (70%) and a testing set (30%), where each CT image was expanded to 20 images by rotation, mirror image, changing brightness, and Gaussian noise. The extended data set included 11,480 CT images. The proposed detection method outperformed three other detection architectures (average precision of 80.3%). For classification, ROI of lymph node metastasis labeled by radiologists were used to train the classification network. The 676 lymph nodes were randomly divided into 70% of the training set (73 benign and 401 malignant lymph nodes) and 30% of the test set (30 benign and 172 malignant lymph nodes). The classification method showed superior performance over other state-of-the-art methods with an accuracy of 96%, true positive and negative rates of 98.8 and 80%, respectively. It outperformed radiologists with an area under the curve of 0.894. The extensive experiments verify the high efficiency of the proposed method. It is considered instrumental in a clinical setting to diagnose cervical LNM with thyroid carcinoma using preoperative CT images. The future research can consider adding radiologists' experience and domain knowledge into the deep-learning based CAD method to make it more clinically significant. The extensive experiments verify the high efficiency of the proposed method. It is considered instrumental in a clinical setting to diagnose cervical LNM with thyroid carcinoma using preoperative CT images.

A low risk of recurrence after breast-conserving surgery for DCIS: A single-institution experience

Background: Previously published studies report up to 30% recurrence rates after DCIS, so it would be desirable to identify those women at risk for recurrence and adapt adjuvant management. This study aimed to identify the locoregional recurrence rate after breast conserving surgery (BCS) for DCIS, and to evaluate the possible role of immunohistochemical (IHC) staining in predicting the risk of recurrence. Patients and methods: In a retrospective cohort study, patients who underwent BCS for pure DCIS were identified. Data on well-established clinical-pathological risk factors and development of locoregional recurrence was gathered from patient files. In addition, IHC stains of ER, PR, HER2, p53, and ki67 were performed on original tumor samples. Univariable Cox regression analyses were performed to identify possible risk factors for locoregional recurrence. Results: 190 patients were included. At a median follow-up time of 12.8 years fifteen (8%) patients developed locoregional recurrence: 7 invasive cancer and 8 DCIS. These recurrences were diagnosed within a range of 1.7 to 19.6 years after the initial diagnosis. Univariable Cox regression analysis did only show a significant association between p53 and locoregional recurrence. Our re-excision rate to obtain free margins was 30.5%, and 90% received radiotherapy. Endocrine treatment was not used. Conclusions: At 12.8 years follow-up, patients with DCIS treated with BCS have a very low locoregional recurrence of 8%. Although we could demonstrate that increased p53 expression is a risk factor for locoregional recurrence, we think this is of little clinical value in our population with such a low recurrence rate. Microabstract: With a published recurrence rate up to 30% after DCIS, it would be desirable to identify those at risk to adapt treatment and follow-up. We aimed to evaluate the role of immunohistochemical staining to determine the risk of locoregional recurrence, in addition to established clinical and pathological risk factors. At a median follow-up of 12.8 years, we found a locoregional recurrence rate of 8%. Increased expression of p53 is associated with an increased risk of locoregional recurrence.

Radiotherapy for cutaneous squamous cell carcinoma: current standards and outlooks

Cutaneous squamous cell carcinoma accounts for 20 % of all malignant non-melanoma skin tumors, which is one of the most common cancers worldwide. Antitumor treatment is usually very effective: cure rate reaches 90 %, while local recurrence rate is 25 %. The main treatment option for primary skin cancers is surgery. The most significant risk factors for locoregional recurrence include tumor location (head and neck), size (&gt;2 cm), depth of invasion (&gt;4 mm), tumor differentiation grade, perineural invasion, immune system disorders (immunosuppression), severe concomitant diseases, and previous treatment.In patients with advanced cutaneous squamous cell carcinoma, 1-year, 2-year, and 3-year survival rates are 50–80, 30–35 and 15–16 %, respectively. Radiotherapy is a radical treatment option that increases the 5-year survival rate to 90 % and ensures good cosmetic results in 80 % of cases. There are 3 main variants of radiotherapy for cutaneous squamous cell carcinoma: sole radiotherapy according to a radical program, adjuvant radiotherapy in combination with surgery, and palliative radiotherapy. most frequently, radiotherapy is used as part of adjuvant postoperative treatment and is not initially considered as a sole conservative treatment for cutaneous squamous cell carcinoma patients below 45 years of age with resectable tumors, especially high-risk tumors. palliative radiotherapy is an affordable and effective method for combating painful symptoms; moreover, it often provides long-term local control.

Recurrence patterns and progression-free survival after chemoradiotherapy with or without consolidation durvalumab for stage III non-small cell lung cancer.

Chemoradiotherapy followed by consolidation durvalumab (CCRT+D) improves survival in patients with stage III non-small-cell lung cancer (NSCLC). We compared recurrence patterns and survival in the CCRT+D and CCRT cohorts. We conducted a multicenter, retrospective study in Japan. Patients who received CCRT for stage III NSCLC were included in this study. Of 178 eligible patients, 136 were in the CCRT+D and 42 were in the CCRT cohorts. Locoregional recurrence (LR), LR plus distant metastases (DM), and DM were observed in 20.6%, 8.8%, 27.9% of the CCRT+D, and 26.2%, 16.7% and 33.3% of the CCRT cohorts, respectively. In-field recurrence was the most common LR pattern in both cohorts. Squamous cell carcinoma and PD-L1 expression < 1%, and female sex and EGFR mutations were significantly associated with an increased risk of LR and DM. In patients with any risk factors for LR, the incidence of LR was similar in the CCRT+D and CCRT (39.5% vs 45.5%). The 24 month progression-free survival (PFS) and overall survival (OS) were 40.3% and 69.4% in the CCRT+D and 24.7% and 61.0% in the CCRT cohorts, respectively. Poor performance status and no consolidation durvalumab were significantly associated with shorter PFS. There was a significant difference in PFS between the CCRT+D and CCRT in the propensity score-matched cohort (HR = 0.51, P = 0.005). In conclusion, consolidation durvalumab decreased both LR and DM, and significantly improved PFS. However, in-field recurrence was still a major problem, as well as DM.

Risk Factors for Local Recurrence in Patients With N1b Papillary Thyroid Carcinoma

Background and Objectives Papillary thyroid carcinoma (PTC) with lateral neck lymph node metastasis is known as a major risk factor for tumor recurrence after surgical treatment. The aim of this study is to identify risk factors for loco-regional recurrence in patients with PTC with lateral neck lymph node metastasis, which has a high risk of recurrence.Subjects and Method This study involved 319 patients who underwent total thyroidectomy, central lymph node (LN) and lateral LN dissection due to PTC. The patients’ demographics and pathological factors, including lymph node metastasis were retrospectively reviewed. Univariate, multivariate and C-index with variable selection analyses were performed to identify factors associated with recurrence-free survival (RFS).Results A mean follow-up of 101 months, 35 (10.9%) patients had a loco-regional recurrence. In multivariate analysis according to loco-regional recurrence, patients with a primary tumor of more than 4 cm, multifocality, vascular invasion, and bilateral lateral cervical metastasis were associated with worse RFS. In the variable selection analysis, lateral lymph node metastasis ratio was also statistically significant.Conclusion PTC with lateral neck lymph node metastasis included tumors larger than 4 cm. Multifocality, vascular invasion, high lateral lymph node metastasis ratio and bilateral neck lymph node metastasis are predictive factors of loco-regional recurrence, and these risk factors should be carefully followed-up after surgery.

PC20. LONG-TERM CANCER RECURRENCE RATES FOLLOWING NIPPLE-SPARING MASTECTOMY: A 10-YEAR FOLLOW UP STUDY

PURPOSE: Although nipple-sparing mastectomy (NSM) is a widely accepted and popular technique, limited data exists examining long-term cancer recurrence rates associated with it. This study sought to analyze rates of breast cancer recurrence in patients who underwent therapeutic NSM with a median of 10 years of follow-up. METHODS: A single institution retrospective review identified all patients who underwent NSM with a median of 10-years of follow-up. Analysis focused on patient demographics, mastectomy specimen pathology, and oncologic outcomes including cancer recurrence. Independent risk factors for locoregional recurrence were assessed via univariate logistic regression. RESULTS: 158 therapeutic NSMs were performed on 152 patients. Invasive ductal carcinoma (48.7%) and ductal carcinoma in situ (35.4%) were the most common tumor types seen on pathology. Multifocal/multicentric disease and lymphovascular invasion were present in 34.1% and 12.8% of specimens, respectively. Sentinel lymph node biopsy rate was 82.9%, with 15.2% reported as positive. Rates of positive frozen and permanent subareolar biopsy were 5.4% and 8.3%, respectively. Low cancer stages were overwhelmingly more common, with stage I and stage 0 representing 40.5% and 35.4% of the population, respectively. Incidence of recurrent disease was 3.2% per mastectomy and 3.3% per patient. Univariate analysis did not identify any variables that were independent risk factors for locoregional recurrence. CONCLUSION: At a median of 10 years of follow-up, overall cancer recurrence rates are low in patients who undergo NSM, further suggesting the safety of this technique. Regardless, close surveillance should remain a goal to ensure prompt detection of any sign of recurrence.

Abstract P3-21-01: A higher locoregional recurrence rate of nipple areolar complex sparing mastectomy with immediate implant reconstruction

Abstract Background The rate of Nipple Areolar Complex (NAC) sparing mastectomy with implant reconstruction is rapidly increasing as the Korean National Health Insurance reimbursed reconstructive surgery for breast cancer patients from 2015. However, only a few reports about oncologic safety have been reported in the absence of large-scale data. We have analyzed the oncologic outcomes of all consecutive breast cancer patients who had NAC sparing mastectomy with immediate implant reconstruction. Methods We used the data from prospectively collected clinical data of patients who underwent immediate implant reconstruction after NAC sparing mastectomy at the National Cancer Center between January 2012 and December 2017. Demographics, clinicopathological characteristics and the follow-up results were analyzed. The statistical analysis was done to infer relations between risk factors and oncologic outcomes such as death, distant metastasis or locoregional recurrence. Results: A total of 538 breasts was analyzed in 486 patients. The mean age of the patients was 44.6 years. The mean BMI was 22.48 kg/m2. The number of bilateral cases was 52 (10.7%) and 135 patients (27.8%) had multiple tumors. Median follow-up was 4.5 years. Molecular subtypes were 373 HR(+)/HER2(-) (69.3%), 31 HR(+)/HER2(+) (5.8%), 76 HR(-)/HER2(+) (14.1%) and 35 HR(-)/HER2(-) (6.5%). Chemotherapy was performed in a total of 212 (43.6%) patients, of which 68 (32.1%) were neoadjuvant and 144 (67.9%) were adjuvant purposes. Trastuzumab was administered to 53 (10.9%) of patients whose tumor size are larger than 1cm under guideline of reimbursement. Postoperative radiotherapy was performed in 131 patients (26.9%). Distant metastasis occurred in 20 patients (3.7%), and seven (1.4%) died. Locoregional recurrence occurred in 43 cases (8.0%) of 538 breasts, including 14 nipples (2.6%) and 12 subareolar lesions (2.2%). Analyzing risk factors related to locoregional recurrence, HR(-)/HER2(+) type showed the highest incidence of 11/76 (14.7%) among four subtypes. The incidence was statistically significantly lower in the group that received postmastectomy radiotherapy than in the group that did not. (6/131 (4.6%) vs 37/355 (10.4%), p=0.001). The node negative group who did not have postmastectomy radiotherapy (31/377 (8.2%)) showed a numerically higher incidence than the node positive group (8/121 (6.6%)). Conclusion Our results showed that NAC sparing mastectomy with immediate implant reconstruction had similar oncologic outcome in terms of overall survival or distant metastasis, however the locoregional recurrence was rather high. Even this is remediable problems we would admit that NAC sparing mastectomy is a bit different from traditional mastectomy. In case that we inevitably apply this operation to relatively young women with multifocal breast cancer, careful consideration would be needed. In addition, identifying risk factors of locoregional recurrence and tailored post-operative radiation therapy are expected to improve the disease-free survival of breast cancer. Citation Format: Ji Young You, Eun-Gyeong Lee, Soo Jin Park, Byeong Nam Kim, Seeyoun Lee, Eun Sook Lee, So-Youn Jung, Youngmi Kwon, Yun Ju Kim, Chan Wha Lee, Tae Hyun Kim. A higher locoregional recurrence rate of nipple areolar complex sparing mastectomy with immediate implant reconstruction [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-21-01.

Factors influencing patterns of recurrence following pancreaticoduodenectomy for patients with distal bile duct cancer and ampulla of Vater cancer.

Backgrounds/AimsPancreaticoduodenectomy (PD) is a standard surgical procedure for patients with periampullary cancer. During the follow-up period after PD, recurrence can be observed in various places with different prognosis. The aim of this study was to clarify the pattern of recurrence and factors affecting the survival of patients with periampullary cancer.MethodsOverall, 88 patients who received PD for distal common bile duct cancer or ampulla of Vater cancer were finally included and their clinical characteristics were analyzed. Patients were divided into three groups: recurrence-free (RF) group, an isolated locoregional recurrence (LR) group, and a distant metastasis (DM) group. Prognostic factors affecting recurrence in each group were analyzed and a survival analysis was performed.ResultsPerineural invasion (PNI), T stage, and lymphovascular invasion (LVI) were significant risk factors for LR and PNI, lymph node metastasis, LVI, and T stage were associated with DM group compared to RF group in univariate analysis, respectively. N stage and PNI were significant risk factors (p = 0.046, p = 0.041) in overall survival of the LR and the DM groups. There was no significant difference in 5-year overall survival between the LR and DM groups.ConclusionsT stage was a significant risk factor of LR, while PNI was a significant risk factor of DM. There was no significant difference in overall survival depending on the site of recurrence.

Perineural Invasion as a Risk Factor for Locoregional Recurrence of Invasive Breast Cancer

<h3>Purpose/Objective(s)</h3> Perineural invasion (PNI) is a pathologic finding observed across a spectrum of solid tumors, typically with adverse prognostic implications. Little is known about how the presence of PNI influences locoregional recurrence (LRR) among breast cancers. We evaluated the association between PNI and LRR among an unselected, broadly representative cohort of breast cancer patients, and among a propensity-score matched cohort. <h3>Materials/Methods</h3> We ascertained breast cancer patients seen at our institution from 2008 to 2019 for whom PNI status and salient clinicopathologic features were available. Fine-Gray regression models were constructed to evaluate the association between PNI and LRR, accounting for age, tumor size, nodal involvement, estrogen receptor (ER), progesterone receptor (PR), HER2 status, histologic tumor grade, presence of lymphovascular invasion (LVI), and receipt of chemotherapy and/or radiation. Analyses were then refined by comparing PNI-positive patients to a PNI-negative cohort defined by propensity score matching. <h3>Results</h3> Among 8,864 invasive breast cancers, 1384 (15.6%) were noted to harbor PNI. At a median follow-up of 6.3 years, 428 locoregional recurrence events were observed yielding a 7-year LRR of 7.1% (95% CI 5.5-9.1) for those with PNI and 4.7% (95% CI 4.2-5.3; <i>P</i> = 0.01) for those without. On univariate analysis throughout the entire cohort, presence of PNI was significantly associated with an increased risk of LRR (HR 1.39, 95% CI 1.08 – 1.78, <i>P</i> < 0.01). Accounting for differences in salient clinicopathologic and treatment parameters by multivariable Fine-Gray regression modeling, the association between PNI and LRR was potentiated (HR = 1.57, 95% CI 1.2 – 2.07, <i>P</i> = 0.001). We further conducted propensity score matching to balance clinicopathologic parameters and treatments between the two groups (PNI vs not), again showing a similar significant association between PNI and LRR (HR = 1.46, 95% CI 1.03 – 2.08, <i>P</i> = 0.034). <h3>Conclusion</h3> PNI is significantly associated with LRR following the definitive treatment of invasive breast cancer. The excess risk conferred by PNI is similar in magnitude to that observed with LVI, or by ER/PR negativity. Breast cancer prognostication and therapeutic decision-making should consider the presence of PNI among other salient risk factors. Larger studies among more uniform breast cancer presentations may elucidate the extent to which these findings apply across breast cancer subtypes and stages.