Extranodal Invasion Research Articles

Nodal Yield in Level II-IV Neck Dissections in Head and Neck Squamous Cell Carcinoma.

The main objective of this study is to analyze factors associated with nodal yield in level II-IV selective neck dissections (NDs) and the secondary objective is to assess its impact on overall and disease-free survival. Observational retrospective study including adult patients submitted to level II-IV ND from January 2015 to December 2021 in the otorhinolaryngology department of a tertiary hospital center. A total of 44 patients and 78 level II-IV NDs (34 bilateral and 10 unilateral) were included. The median age at diagnosis was 60(22-74) years, and 93.2% of the patients were male. A lower nodal yield was significantly associated with previous radiotherapy (p = 0.042) and extranodal invasion (p < 0.001) and was non-significantly associated with older age (p = 0.065). Furthermore, on a Cox analysis adjusted to the cN status and age, the nodal yield was not associated with five-year disease-free survival (HR = 0.986; 95% CI = 0.922-1.054; p = 0.681) nor with five-year overall survival (HR = 1.006; 95% CI = 0.925-1.095; p = 0.888). A reduced nodal yield in level II-IV NDs was significantly associated with previous radiotherapy and extranodal extension and non-significantly associated with age. There was no association between the nodal yield and five-year overall survival or disease-free survival.

Clinicopathological study on diameter of extranodal extension of cervical metastatic lymph nodes in the prognosis of oral cancer

ObjectivesTo investigate the relationship between the degree of destruction of the cervical lymph node capsule, extranodal invasion distance, and the prognosis of extranodal extension (ENE)-positive patients Study designWe retrospectively examined microscopic slides from neck dissection specimens of ENE-positive patients of our hospital. The ENE distance was measured by a pathologist who set up a virtual lymph node and measured the maximum extranodal invasion distance. The maximum distance was used for multiple ENEs. Forty patients with ENE were enrolled in this study. The Kaplan–Meier method was used to estimate survival. ResultsAmong the ENE-positive cases, the capsule was completely destroyed and partially destroyed in seven and 33 cases, respectively. Disease-specific survival (DSS) was 1251 days (range 156–3009 days). The median distance of extranodal invasion was 2500 µm (392–8500 µm) in the 33 ENE-positive cases in which the capsule was not completely destroyed. Receiver operating characteristic curve analysis of these 33 cases showed that the cutoff value of extranodal invasion distance for progression-free survival was 2241 µm. ConclusionsENE is a prognostic predictor of oral cancer; ENE was an independent prognostic factor; and ENE size cutoff of 2241 µm was a significant prognostic factor.

Clinical calculator based on CT and clinicopathologic characteristics predicts short-term prognosis following resection of microsatellite-stabilized diffuse gastric cancer.

Although microsatellite stability/Epithelial-mesenchymal transition (MSS/EMT) subtypes have been reported in multiple cancer prognosis studies, strong confounding factors between MSS/EMT (usually with Lauren's diffuse phenotype) and diffuse gastric cancer (GC) may obscure the independent prognostic value of diffuse GC. Additionally, recent studies suggest a strong correlation between mural stratification based on CT and diffuse GC. This study aims to investigate potential prognostic factors of MSS diffuse GC using mural stratification and to develop a risk assessment model. This retrospective study included 131 patients with MSS diffuse GC who underwent radical surgery. Univariate and multivariate Cox proportional hazards regression analysis was used to identify model predictors and construct a nomogram for overall survival (OS) and recurrence-free survival (RFS) risks. The model's performance was evaluated using ROC, accuracy, and C-index. Internal validation of the model was conducted using the bootstrap resampling method. Among 131 cases, 60 cases (45.8%) exhibited grade 2 mural stratification, which correlated with a poorer tumor prognosis and a more invasive phenotype. Furthermore, a nomogram for predicting OS and RFS prognosis was established based on multivariate results (age, extranodal invasion, mural stratification, and/or P53). The nomogram demonstrated excellent performance, with an AUC of 0.859 (95% CI 0.794-0.924) for OS and 0.859 (95% CI 0.789-0.929) for RFS. Internal validation using 1000 bootstrap samples yielded AUC values of 0.845 and 0.846 for OS and RFS, respectively. Grade 2 mural stratification based on CT imaging revealed a more aggressive invasive phenotype, characterized by increased LN metastasis, higher rates of peritoneal metastasis, and a poorer short-term prognosis. Furthermore, the CT phenotype-based nomogram demonstrates favorable discrimination and calibration, enabling convenient individual short-term prognostic evaluation following resection of MSS diffuse GC.

Enhancing survival outcomes in stage Ⅲ gastric/esophagogastric junction cancer: a retrospective study of immune checkpoint inhibitors and adjuvant chemotherapy based on real-world data

Objective: To explore the efficacy of immune checkpoint inhibitors combined with adjuvant chemotherapy in patients with phase III gastric cancer and esophagogastric junction cancer. Methods: This study used a retrospective cohort study method based on real-world data. Clinical data of 403 patients with stage III gastric/esophagogastric junction cancer who underwent gastrectomy followed by adjuvant therapy in the Department of Gastric Surgery at Sun Yat-sen University Cancer Center from January 2020 to December 2023 were retrospectively collected. The study cohort comprised 147 (36.5%) patients with stage IIIA, 130 (32.3%) with stage IIIB, and 126 (31.3%) with stage IIIC gastric/esophagogastric junction cancer. Of them, 15 (3.7%) were HER-2 positive, 25 (6.2%) dMMR, and 22 (5.5%) patients Epstein-Barr virus encoding RNA (EBER) positive. Based on treatment plans, the patients were divided into immune checkpoint inhibitor combined with chemotherapy group (immune therapy group, n=110, 71 males and 39 females, median age 59 years old) and chemotherapy alone group (chemotherapy group, n=293, 186 males and 107 females, median age 60 years old). All patients in the immunotherapy group received immune checkpoint inhibitors targeting the programmed cell death protein-1 (PD-1) and its ligand (PD-L1). Of them, 85 received pembrolizumab, 10 received sintilimab, 8 received tislelizumab, 4 received camrelizumab, 2 received toripalimab, and 1 received pabocizumab. The adjuvant chemotherapy regimens used among the chemotherapy alone group includes SOX regimen (132 cases), XELOX (102 cases), S-1 monotherapy (44 cases), and other regimens (15 cases). The 3-year DFS rate of the two groups was compared, and subgroup analysis was conducted based on different ages, molecular phenotypes, pTNM staging, extranodal infiltration, and tumor length. Results: The median follow-up was 20.5 months (range 3.1~46.3), with a 3-year overall DFS rate of 61.4% for the entire 403 patients. The 3-year DFS rate for the immunotherapy group was 82.7%, higher than the chemotherapy alone group (58.8%), with a statistically significant difference (P=0.021). Multivariate analysis showed that postoperative immunotherapy was a protective factor for DFS (HR=0.352, 95%CI: 0.180~0.685). Subgroup analysis showed that stage IIIC (HR=0.416, 95%CI: 0.184~0.940), aged ≥60 years (HR=0.336, 95%CI: 0.121~0.934) and extranodal invasion (HR=0.378, 95%CI: 0.170~0.839) were associated with benefit from the combined immune adjuvant chemotherapy, while no association was observed for MMR, HER-2 or EBER status. Conclusion: Stage III gastric/esophagogastric junction cancer patients may benefite from postoperative immune checkpoint inhibitor combined with adjuvant chemotherapy in real-world settings.

Effect of L-Type Amino Acid Transporter 1 Expression on Clinicopathological Features and Prognosis of Non-Hodgkin's Lymphoma

To detect the expression of L-type amino acid transporter 1 (LAT1) in non-Hodgkin's lymphoma (NHL) tissues, and analyze its effect on clinicopathological characteristics and prognosis of patients. A total of 92 NHL patients who were treated in our hospital from January 2017 to April 2019 were collected. The expression of LAT1 in NHL tissue was detected by immunohistochemistry and compared between patients with different pathological features (including sex, Ann Arbor stage, extranodal infiltration, Ki-67). The risk factors affecting mortality were analyzed using univariate and multivariate Cox proportional hazards regression. Receiver operating characteristic (ROC) curve was used to detect the predictive value of percentage of LAT1-positive cells in NHL tissue for patient mortality, and analyzing the effect of percentage of LAT1-positive cells on survival rate. LAT1 was positively expressed in NHL tissue. The high expression rate of LAT1 in Ann Arbor stage III and IV groups were higher than that in Ann Arbor stage I group, that in extranodal infiltration group was higher than non-extranodal infiltration group, and that in Ki-67 positive expression group was higher than Ki-67 negative expression group (all P < 0.05). The remission rate after 3 courses of treatment in high-LAT1 expression group was 70.7%, which was lower than 91.2% in low-LAT1 expression group (P < 0.05). Ann Arbor stage III and IV, extranodal invasion, Ki-67 positive expression and increased expression of LAT1 (LAT1-positive cell percentage score ≥2) were risk factors for mortality. The cut-off value of percentage of LAT1-positive cells for predicting NHL death was 45.6%, and the area under the ROC curve was 0.905 (95%CI: 0.897-0.924). The 3-year survival rate of high-LAT1 level group (the percentage of LAT1-positive cells≥45.6%) was 50.00%, which was lower than 78.26% of low-LAT1 level group (P < 0.05). The expression level of LAT1 in NHL tissue increases, which affects Ann Arbor stage and extranodal infiltration of patients. LAT1 is a risk factor for death.

Prognostic analysis of prostaglandin D2 synthase in diffuse large B-cell lymphoma

PurposeWe aimed to analyse the correlation between prostaglandin D2 synthase (PTGDS) and a diffuse large B-cell lymphoma (DLBCL) prognosis.MethodsWe retrospectively collected two hundred paraffin-embedded tissue specimens that were pathologically diagnosed as DLBCL in the Fujian Tumour Hospital between January 2014 and December 2018. An abundance of paraffin-embedded tumour tissues were obtained. Twenty patients with lymphocyte-rich, benign, tissue-reactive, hypertrophic tonsillitis were selected as controls. Wax blocks were selected for primary cases and the controls were screened by professional pathologists. The levels of prostaglandin D2 synthase (PTGDS) and the EMT-related molecules, E-cadherin and vimentin, were detected by immunohistochemistry in clinical samples. A chi-square test revealed the correlations between PTGDS expression and clinicopathological characteristics, including age, sex, primary site, clinical stage, immunotyping, and International Prognostic Index (IPI) score. The Kaplan–Meier survival analysis was performed, and the diagnostic value was evaluated by receiver operating characteristic (ROC) curve analysis.ResultsA total of 138 cases (69%) were found to be PTGDS positive (> 30% positive cells). PTGDS staining was negative (< 30% positive cells) in 62 cases (31%). We collected the corresponding clinicopathological information and found that PTGDS expression was not significantly related to the patients’ age, tumour stage, presence of extranodal invasion, or IPI score. According to the follow-up data, patients with low PTGDS expression had poor progression-free survival (PFS) and overall survival (OS), with 2-year PFS and OS rates of 41.7% and 50%, respectively. The 2-year PFS and OS rates of PTGDS-positive patients were 89.3% and 92.9%, respectively (P < 0.0001), and the differences were significant.ConclusionWe found that the expression level of PTGDS is significantly correlated with the prognosis of diffuse large B-cell lymphoma.

Comparison of Clinical and Pathological Staging in Patients with Head and Neck Cancer After Neck Dissection.

Introduction Clinical and pathological staging plays an important role on the prognosis of head and neck cancer (HNC) patients. Objective The present study aims to compare clinical and pathological T, N and overall staging in patients with HNC, to identify factors associated with these discrepancies, and to analyze and compare survival or disease-free survival in staging disagreements. Methods Retrospective cohort including every patient submitted to neck dissection from January 2010 to December 2020 in the department of Otorhinolaryngology of a tertiary hospital center. Results A total of 79 patients were analyzed; their mean age was 58.52 ± 13.15 years old and 88.9% were male. Assessing overall staging, discrepancies were noted in 53% (36.4% upstaging and 16.6% downstaging) and were significantly associated with clinical overall staging ( p = 0.006). Regarding T staging, differences were noted in 45.5% (30.3% upstaging and 15.2% downstaging) and were significantly associated with imaging modality ( p = 0.016), clinical T staging ( p = 0.049), and histology ( p = 0.017). Discrepancies in N staging were noted in 38% (25.3% upstaging and 12.7% downstaging) and were significantly associated with age ( p = 0.013), clinical N staging ( p < 0.001), and presence of extranodal invasion ( p < 0.001). Both in Overall, T, and N staging, the aforementioned disagreements were not associated with either higher mortality or higher disease relapse. Conclusion Overall, T, and N staging disagree in an important number of cases, and the overall stage can disagree in up to 53% of the cases. These disagreements do not seem to influence overall and disease-free survival.

Utility of adjuvant radioactive iodine therapy after reoperation in papillary thyroid carcinoma with cervical lymph node recurrence.

The aim of this study was to evaluate the utility of RAI therapy after reoperation for patients with LN relapse. We retrospectively evaluated PTC patients who had undergone reoperation due to cervical LN recurrence. We used the chi-square test, Fisher's exact test, Student's t test and the Mann-Whitney U test to compare characteristics between patients retreated with RAI and those who did not receive RAI after reoperation. A multivariate logistic regression model was used to determine the association between RAI and biochemical response. By means of the Kaplan-Meier estimator and a multivariate Cox proportional hazard model, we assessed whether administration of RAI after reoperation is associated with improved prognosis. RAI therapy was closely associated with a superior biochemical response in all selected patients according to both univariate (p = 0.012) and multivariate analyses (p = 0.020). Thirteen of 97 patients developed a second recurrence or progression of structural disease during follow-up. A Kaplan-Meier progression-free survival (PFS) curve showed that high post-retreatment thyroglobulin (Tg) levels (≥ 1ng/mL) were associated with unfavourable prognosis (p = 0.0172). In the subgroup analysis, univariate analysis revealed that only patients without extranodal invasion who received adjuvant RAI therapy achieved better PFS than those who did not receive RAI therapy (p = 0.0203). Multivariate analysis showed that RAI (p = 0.045) also improved PFS in patients without extranodal invasion. Adjuvant RAI after reoperation for PTC recurrence/persistence was associated with a favourable biochemical response and tended to increase PFS. Specifically, it was significantly associated with improved PFS only in patients without extranodal extension.

Abstract P3-05-56: The clinical impact of preoperatively needle-aspiration biopsy for axillary lymph nodes in T1-T2 breast cancer patients with axillary lymph node metastasis

Abstract Introduction: More than half of the results of axillary lymph node dissection followed by metastasis in sentinel lymph node(SLN) biopsy are negative. For deescalating axillary surgery, it is necessary to predict the non-SLN metastasis state, where metastasis was confirmed in the SLN biopsy. Method: Breast cancer patients with T1 and T2 stage were retrospectively reviewed from January 2008 to December 2016. A total of 818 patients underwent surgery as the primary treatment and the result of SLN biopsy was positive for metastasis. Patients who skipped SLN biopsy procedure and were proven metastatic axillary lymph nodes by needle-aspiration biopsy (NAB) were excluded. SLN was defined as lymph nodes detected by the dual method with hot-uptake by radioisotope and dyed by blue dye, or lymph nodes with palpable or suspected metastatic findings during SLN biopsy. Clinicopathological factors including and extra-nodal invasiveness were analyzed. Result: The median follow-up period was 73 months. Non-SLN metastasis was significantly seen in patients with older than 50 years, positive node metastases by preoperative NAB, high T stage, and extra-nodal invasion. In subgroup analysis, patients who underwent total mastectomy had the similar patterns of the increased risk of having non-SLN. Poor overall survival was observed in the patients with the presence of non-SLN metastasis. Conclusion: We confirmed predictive factors with a high probability of non-SLN metastasis. Axillary lymph node dissection cannot be overlooked in the patients proven the metastatic result of preoperative NAB. Citation Format: Jee Hyun Ahn, Suk Jun Lee, Jieon Go, Hyung Seok Park, Jee Ye Kim, Seung Il Kim, Byeong Woo Park, Seho Park. The clinical impact of preoperatively needle-aspiration biopsy for axillary lymph nodes in T1-T2 breast cancer patients with axillary lymph node metastasis [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 P3-05-56.

Clinical and endoscopic characteristics of gastrointestinal mantle cell lymphoma

Objective: To study the clinical and endoscopic features of mantle cell lymphoma (MCL). Methods: The clinical data and endoscopic characteristics of 20 patients with gastrointestinal MCL treated in the Affiliated Hospital of Zunyi Medical University and the Digestive Endoscopy Center of Guizhou Medical University from January 2011 to January 2021 were collected, and the histological and immunohistochemical characteristics of the tumor were observed. Meanwhile, 44 cases of non-gastrointestinal MCL in the above two hospitals in the same period were also enrolled. The clinical and endoscopic differences between the two groups were compared. Results: Among the 20 patients with gastrointestinal MCL, the male to female ratio was 4∶1 (16/4), the average age was (60.3±9.7) years, and 11 patients (55.0%, 11/20) were over 60 years old. The main clinical manifestations of 20 patients at the onset of the disease were bloody stool or black stool in 9 cases (45.0%), abdominal pain in 8 cases (40.0%). Moreover, 5.0% (1/20) had B symptoms (fever, night sweat and weight loss). The most frequently involved site was colorectum (50.0%). Endoscopic findings showed mucosal polypoid lesions in 13 cases (65.0%, 13/20), involving multiple intestinal segments, with polyp diameter of 0.2-3.5 cm. Two cases (10%) were in stage Ⅲ and 18 cases (90%) were in stage Ⅳ according to Ann Arbor staging. Seven cases (35.0%, 7/20) had the involvement of the peritoneal and retroperitoneal lymph nodes, 9 cases (45.0%, 9/20) had the involvement of the superficial lymph nodes in 45.0% (9/20), and 4 cases (20%, 4/20) had other extranodal invasion. Splenomegaly accounted for 35.0% (7/20). CD20, Bcl-2 and CD5 were positive or strongly positive in all gastrointestinal MCL tumor cells in 20 cases. Cyclin D1 was positive or strongly positive, accounting for 90.0% (18/20). The sex-determining region of Y chromosome-related high-mobility-group box 11 (SOX11) was positive or strongly positive, accounting for 65.0% (13/20). The positive index of Ki-67 was 5%-80%. Twenty cases (100%, 20/20) were followed up. The median follow-up was 41.2 months (1-74 months). There was no significant difference in the 3-year overall survival rate between the gastrointestinal MCL patients (70.0%) and non-gastrointestinal MCL patients (72.7%) (χ2=0.051, P=0.822). Conclusions: Abdominal discomfort is the main symptom of gastrointestinal MCL, which often occurs in the colorectum and often presents with multiple polypoid lesions. There are relatively few cases with B symptoms and extranodal invasion, and the prognosis is not different from that of patients with non-gastrointestinal MCL.

ODP532 Fractionated Radioactive Iodine Therapy in Management of Differentiated Thyroid Cancer

Abstract Introduction Management of differentiated thyroid cancer (DTC) requires individualized treatment plans that are tailored to the risk of disease recurrence. Radioactive iodine treatment (RIT) remains a treatment modality that is valuable in certain patients with DTC. The lack of institutional availability and travel bans imposed by the COVID-19 pandemic did not allow a subset of our patients to get intermediate or high-dose RIT. As an alternative, fractionated low-dose RITs given over a short time interval have been used. We aim to study the response to therapy in this patient population. Materials and methods This retrospective study was performed at a tertiary care hospital in Qatar. Between 2015-2020, patients who completed at least 2 doses of low-dose RIT within 6-12 months with at least one staging visit 3-6 months after their last treatment were included in the study. Results 69 patients met our inclusion criteria, 30 (43.5%) of whom were males and 39 (56.5%) females. The mean age at diagnosis was 40.7 +/- 9.35 years. Classic papillary thyroid cancer was the predominant histological variant (76.6%). Based on surgical pathology, the initial risk of disease recurrence was high in 24 (34.8%) patients, intermediate in 21 (30.4%) patients, and low in 21 (30.4%) patients. 3 (4.3%) patients did not have complete data for classification. Lymphatic invasion was noted in 16 (23.2%), vascular invasion in 15 (21.7%), positive margins in 30 (43.5%) and extra-nodal invasion in 10 (14.5%) patients. Patients underwent between 2-6 fractionated RITs, with the majority having undergone 2. In the low-risk group, 9 (42.9%) patients had an excellent response to therapy at last follow-up, 3 (14.3%) had the persistent structural disease, and 9 (42.8%) patients had an indeterminate response. In the intermediate-risk group, 7 (33.4%) patients had excellent response, 2 (9.5%) had the biochemically persistent disease, 8 (38.1%) had the structurally persistent disease, and 4 (19%) had an indeterminate response. In the high-risk group, 5 (20.8%) patients had excellent response, 13 (54.2%) had a structurally persistent disease, and 6 (25%) patients had an indeterminate response to therapy. Conclusion A similar response to therapy has been reported in the literature in the low and high-risk recurrence groups, suggesting that additional RIT may not be beneficial. In the intermediate risk of recurrence group, there is a higher percentage of patients with structural evidence of disease compared to what is reported in the literature, suggesting that perhaps a single intermediate or high dose RIT may be more beneficial. Either way, the c urrent management of DTC should be based on dynamic risk assessment to guide the need for further therapies. Presentation: No date and time listed

627MO Orelabrutinib plus RCHOP for previously untreated non-germinal center b cell-like (GCB) diffuse large b cell lymphoma (DLBCL) patients with extranodal disease

The prognosis of patients with non-GCB DLBCL is poor, especially in those with extranodal invasion which has strong invasiveness and rapid clinical progress. How to improve the prognosis of these patients is the main challenge of DLBCL therapy. Bruton tyrosine kinase (BTK) is a member of the non-receptor tyrosine kinase Tec family; it is involved in the proliferation, adhesion and metastasis of B cells. BTK inhibitor showed activity in relapsed/refractory non-GCB DLBCL. Orelabrutinib is a new oral covalent BTK inhibitor; this study aimed to analyze the efficacy and safety of orelabrutinib plus RCHOP for previously untreated non-GCB DLBCL patients with extranodal disease.

Differences in the clinical characteristics of papillary thyroid microcarcinoma located in the isthmus ≤5 mm and >5mm in diameter.

BackgroundThe optimal treatment of papillary thyroid microcarcinomas (PTMCs) located in the isthmus (iPTMCs) is still controversial. The purpose of this study was to compare the clinicopathologic features of patients with iPTMCs ≤5 mm and >5 mm in diameter after total thyroidectomy, and to identify the risk factors for recurrence in patients with iPTMCs.MethodsA total of 102 iPTMC patients who underwent total thyroidectomy were reviewed retrospectively. The clinicopathologic characteristics of iPTMCs ≤5 mm group (n = 29) have been compared with a group >5 mm (n = 73). Univariate and multivariate Cox proportional hazard models served to identify risk factors associated with recurrence-free survival (RFS).ResultsGender (p = 0.033), multifocality (p = 0.041), and central lymph node metastasis (CLNM) (p = 0.009) of patients in the ≤5 mm and >5 mm groups differed significantly. iPTMC patients with age <55 years, male, multiple tumor, and extrathyroidal extension showed comparatively more frequent of CLNM in >5 mm groups. Of the 102 patients, nine (8.8%) developed recurrence during follow-up (median: 49.5 months). The patients with recurrences had comparatively high rates of CLNM (p = 0.038), extranodal invasion (p = 0.018), and more MNCND (Metastasis Nodes for Central Neck dissection) (p = 0.020). A cutoff of MNCND >2.46 was established as the most sensitive and specific level for the prediction of recurrence based on receiver operating characteristic (ROC) curve analyses. Multivariate analysis showed that the number of MNCND ≥3 was an independent predictor of poor RFS (p = 0.028).ConclusionWe have found that the recurrence rates are similar in patients with iPTMCs ≤5 mm and >5 mm. The iPTMCs >5 mm were more likely to be associated with pathological features such as multifocality and CLNM. The male gender, extrathyroidal extension, and CLNM were associated with recurrence of iPTMCs except for tumor size and multifocality. Higher risk of CLNM should be considered in iPTMC >5 mm when it reaches some risk factors. The numbers of MNCND ≥3 may be an independent predictor for recurrence, which could help clinicians for the decision of radioiodine administration and the modulation of follow-up modalities.

Clinical and biological characteristics of non-IgM lymphoplasmacytic lymphoma

目的探索非IgM型淋巴浆细胞淋巴瘤（LPL）患者的临床及生物学特征。方法回顾性收集中国医学科学院血液病医院1993年7月至2020年8月收治的340例LPL患者的临床资料，其中23例为非IgM型LPL组，317例为华氏巨球蛋白血症（WM）组。比较两组患者的临床及生物学特征。结果23例非IgM型LPL患者中，2例分泌单克隆性IgA，14例分泌单克隆性IgG，7例不分泌单克隆性免疫球蛋白。非IgM型LPL和WM患者中位年龄均为62（35～81）岁。与WM组患者相比，非IgM型LPL组患者女性（56.5％对27.3％，P＝0.007）、脾大（60.1％对43.8％，P＝0.100）、结外侵犯（21.7％对12.3％，P＝0.672）比例更高。非IgM型LPL组18例患者进行了MYD88基因相关检测，阳性率55.6％。非IgM型LPL组17例患者接受了治疗，启动治疗的患者比例与WM组患者相当（94.4％对92.7％，P＝0.488）。非IgM型LPL组16例患者进行了疗效评价，一线治疗总体缓解率87.5％，中位随访时间33.9（3.5～125.1）个月，总体中位无进展生存（PFS）、总生存（OS）时间未达到，3年PFS率和OS率分别为71.4％和68.9％。WM组中位PFS、OS时间分别为66.2个月和78.1个月。两组PFS、OS的差异均无统计学意义（P值分别为0.340、0.544）。结论非IgM型LPL与WM患者的临床及生物学特征相似，但非IgM型LPL组女性、结外受累比例更高。非IgM型LPL患者的生存及预后与WM患者相似。

Pathological characteristics and clinical prognosis of nodular sclerosis grade 2 of classic Hodgkin's lymphoma

Objective: To investigate the pathological characteristics and clinical prognosis of nodular sclerosis grade 2 of classic Hodgkin's lymphoma (cHL-NS2) in our cancer center. Methods: A retrospective collection of 23 cases of cHL-NS2 admitted in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from July 2008 to April 2019 was performed. Fifty-five cases of nodular sclerosis grade 1 of classical Hodgkin's lymphoma (cHL-NS1) during the same period were selected as control group. Survival curves were plotted using the Kaplan-Meier method, and Cox regression model was used to analyze the influencing factors for survival. Results: The median age of 23 cases of cHL-NS2 was 30 years old. Five cases had extra nodal invasion, and 19 cases were Ⅰ-Ⅱ stage based on Ann Arbor system. The pathological morphology of cHL-NS2 showed that the lymph node structure was completely destroyed and was divided into nodules by thick collagen. The tumor cells in the nodules were abundant and proliferated in sheets. The boundaries between the tumor cells were not clear. The incidence of tumor necrosis in cHL-NS2 was 43.5% (10/23), which was significantly higher than 18.2% (10/55) in cHL-NS1 (P=0.040). The 3-year progression-free survival (PFS) rate of patients in the cHL-NS2 group was 58.1%, which was significantly lower than 89.7% in the cHL-NS1 group (P=0.002). In all of 78 cases, the 3-year PFS rate of patients who did not obtain complete response (CR) was 67.1%, which was significantly lower than 92.2% in patients who achieved CR (P=0.030). Multivariate Cox regression analysis demonstrated that both cHL-NS2 and failure to obtain CR by first-line treatment were independent indicators for short PFS time (P<0.05). Conclusions: In cHL-NS2, the morphology of tumor cells are diverse, and tumor necrosis can be easily found. Under the current first-line treatments of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), cHL-NS2 is an independent indicator for worse PFS.

Abstract 669: Nuclear FAK drives thyroid cancer growth and survival

Abstract Background: Late stage thyroid cancers characterized by metastasis and extranodal invasion have a poor prognosis compared to those with localized disease. However, there are limited therapeutic options and few biomarkers to indicate which patients will develop aggressive disease. Our lab has identified Focal Adhesion Kinase (FAK) as a key regulator of thyroid cancer growth, invasion, and metastasis. FAK is a non-receptor tyrosine kinase that is auto-phosphorylated at tyrosine 397 (Y397) in response to integrin or growth factor receptor signaling resulting in the activation of downstream signaling pathways. While FAK is predominantly localized at the plasma membrane, FAK has also been shown to accumulate in the nucleus via a nuclear localization sequence (NLS) to promote cell survival. We have found that FAK localizes to the nucleus in a subset of thyroid cancer patient tumors and that phosphorylated Y397 FAK (pY397 FAK) specifically accumulates in the nucleolus. The nucleolus plays a key role in cancer progression through the synthesis of ribosomal RNA (rRNA) and subsequent increase in ribosome biogenesis, protein synthesis, and tumor growth. It is unclear how pY397 FAK localizes to the nucleolus and what the function of pY397 FAK is in the nucleolus. Hypothesis: Nuclear FAK drives thyroid cancer growth and survival through the phosphorylation of nucleolar proteins involved in rRNA transcription. Results: To address the functional role of FAK in the nucleus, we excluded FAK from the nucleus by mutating its NLS and found that it significantly decreased anchorage independent growth compared to wild type (WT) FAK in our thyroid cancer cells (BCPAP and 8505C). Importantly, non-phosphorylatable FAK mutant (Y397F) and kinase dead FAK mutant also decreased growth indicating that nuclear and pY397 FAK are required for anchorage independent growth. Furthermore, we found that forcing FAK into the nucleus with an SV40 NLS resulted in increased FAK nucleolar accumulation which was eliminated when FAK is forced into the nucleus with Y397F FAK. These data indicate that pY397 FAK is required for FAK nucleolar accumulation. To investigate the role of pY397 FAK in the nucleolus, we performed BioID to identify novel protein-protein interactions for WT FAK and Y397F FAK. We found that pY397 FAK interacts with a network of nucleolar proteins including NPM1, TOP1, and DDX46. Interestingly, the majority of these nucleolar proteins are involved in transcription of pre-rRNA which is essential for protein synthesis and growth. Of note, Nucleophosmin 1 (NPM1) is an endoribonuclease that regulates pre-rRNA synthesis through the cleavage of the 46S rRNA transcript. We confirmed that pY397 FAK specifically interacts with NPM1 by Proximity Ligation Assay. Conclusion: These data indicate that pY397 FAK interacts with a network of nucleolar proteins involved in rRNA transcription and that nuclear pY397 FAK drives growth and survival in thyroid cancer. Citation Format: Meghan Kellett, Vibha Sharma, Brittelle Kessler, Sharon Sams, Molishree Joshi, Rebecca E. Schweppe. Nuclear FAK drives thyroid cancer growth and survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 669.

UPFRONT SURGERY AS FIRST-LINE TREATMENT IN PATHOLOGICAL N2 NON-SMALL CELL LUNG CANCER

TYPE: Abstract TOPIC: Lung Cancer PURPOSE: Multimodality therapy offers highest chance of improving prognosis in pN2 NSCLC. PURPOSE: to determine the long-term clinical outcomes and prognostic variables associated with upfront surgery as first-line therapy in pN2. METHODS: Retrospective evaluation of pN2 NSCLC underwent surgery (2007-2017). Patients with concurrent malignancies, neoadjuvant therapy; partial surgical resection; and insufficient data were excluded. Multidisciplinary team devised treatment methods for biopsy-confirmed N2 disease. Upfront surgery was considered if initial tumour was resectable, mediastinal nodal metastases were limited to single station, and there was no evidence of extra-nodal tumour invasion. RESULTS: Cox proportional hazards analysis revealed that older age and number of comorbidities were substantially linked with poorer OS. Mean duration of follow-up was 39.6 24.7 months. At conclusion of follow-up , 127 (44.6%) patients had died. Median overall survival (OS) for induction chemotherapy group was 49 months [95%CI: 38–70 months], and 5-year OS rate was 44.4%. Median and 5-year OS for patients who underwent upfront surgery were 66 months (95%CI: 40–119) and 66.3%, respectively. No statistically significant differences in treatment techniques were observed (p=0.48). At 5-years, DFS for induction chemotherapy was 17% (95%CI: 11–25) and upfront surgery was 22% (95%CI: 9–32%); there were no statistically significant differences between groups (p = 0.93). No significant variations in survival were identified according to clinical N status (OS, p=0.36; DFS, p=0.65). CONCLUSIONS: In patients with pN2 NSCLC, upfront surgery as first-line therapy resulted in favourable clinical results. CLINICAL IMPLICATIONS: In resectable N2 NSCLC, upfront surgery should be considered as one of the multimodality treatment choices. DISCLOSURE: Nothing to declare. KEYWORD: lung cancer

18F-FDG PET/CT concurrent with first radioiodine post-therapeutic scan in high risk differentiated thyroid cancer: a useful tool or just an expensive diversion?

Aim of the present study was to evaluate the clinical impact of fluorine-18F-fluorodeoxyglucose PET/CT (18F-FDG-PET/CT) concurrent with post-therapeutic whole-body radioiodine scan (TxWBS) after first radioiodine (RAI) treatment in patients with high-risk differentiated thyroid carcinoma (DTC). This was a retrospective, single-center study including 39 patients with DTC (22 females, 17 males, median age 54; IQR: 35-60 years, 87% papillary thyroid cancer, 13% follicular thyroid cancer). All patients underwent 18F-FDG-PET/CT and RAI treatment, both performed off L-T4 about 3 months after total thyroidectomy. TxWBS was obtained 3 days afterwards using planar technique and SPECT/CT of neck and thorax regions. Semiquantitative analysis was performed on positive 18F-FDG-PET/CT scans to assess SUV<inf>max</inf>, SUV<inf>ratio</inf>, MTV and TLG values in target lesions (hottest 18F-FDG-positive lesion present in each patient). Receiver operating characteristics (ROC) curve analysis was obtained to establish a cut-off point for SUV<inf>max</inf> able to predict the presence of RAI nonavid lesions. Univariate and multivariate analyses were executed to find out predictive factors for abnormal 18F-FDG-PET/CT imaging. In 11 (28%) patients 18F-FDG-PET/CT and TxWBS were both negative and in 9 (23%) both positive, showing loco-regional or distant metastases. In 14 patients (36%) 18F-FDG-PET/CT showed more lesions than TxWBS, while in 5 (13%) patients more lesions were present at TxWBS than 18F-FDG-PET/CT. Overall, 23 patients (59%) showed 18F-FDG avid lesions and 18F-FDG-PET/TC changed the management in 14 (36%), including the choice to perform RAI therapy with higher activities than expected, lymph-node dissection for loco-regional metastases, direct therapy for solitary bone metastases. Through ROC curve analysis, a value superior to 7.25 of SUV<inf>max</inf> was able to predict the presence of RAI non-avid lesion at TxWBS. Serum stimulated thyroglobulin and extranodal invasion resulted to be risk factors for abnormal 18F-FDG-PET/CT imaging. However, only extranodal invasion turned out to be an independent risk factor for abnormal 18F-FDG-PET/CT. The present study demonstrated the clinical value of RAI-concurrent 18F-FDG-PET/CT in patients with high-risk DTC. However, some questions remain open, including the pretherapeutic thyroglobulin level to use as indication to 18F-FDG-PET/CT and the predictive value of 18F-FDG-PET/CT semiquantitative parameters.

The Mutation of BTG2 Gene Predicts a Poor Outcome in Primary Testicular Diffuse Large B-Cell Lymphoma.

IntroductionPrimary testicular diffuse large B-cell lymphoma (PT-DLBCL) is a rare and aggressive form of mature B-cell lymphoma commonly found in elder males, but its genetic features are poorly understood. In this study, we had performed target-sequencing of 360 lymphoma-related genes on 76 PT-DLBCL patients with a median age of 65 (33–89). Our data provide a comprehensive understanding of the landscape of mutations in a small subset of PT-DLBCL.MethodsA total of 76 PT-DLBCL patients were sequenced, and their clinical data and follow-up data were collected. The relationship between mutated genes, clinical data and prognosis and survival of PT-DLBCL patients was retrospectively analyzed by statistical software.ResultsWe observed a median of 15 protein-altering variants per patient in our data and was identified recurrent oncogenic mutations of 360 lymphoma-related genes involved in PT-DLBCL, including PIM1 (74%), MYD88 (50%), KMT2D (38%), KMT2C (34%), BTG2 (34%), TBL1XR1 (34%) and ETV6 (24%). Compared with classic DLBCL, PT-DLBCL showed an increased mutation frequency of PIM1, MYD88, BTG2, while NOTCH1 appeared exclusive mutated with PIM1, MSH3 and ETV6. Cox risk model regression analysis showed that age ≥60 years, IPI 3–5 points, BTG2 gene mutation and extranodal organ invasion suggested poor prognosis. Finally, we constructed an OS predict model of PT-DLBCL patients using above factors with a high accuracy.ConclusionIn conclusion, our results revealed genomic characterization of PT-DLBCL, and the mutation of BTG2 was an independent factor predicting a poor prognosis.

Calcification and Expression of Bone Morphogenetic Protein-4 in Papillary Thyroid Carcinoma

Background/Aim: The purpose of this study was to investigate whether bone morphogenetic protein (BMP)-4 expression differs according to the presence of calcification in papillary thyroid carcinoma and to investigate if calcification and BMP-4 expression are associated with metastasis of papillary carcinoma.Methods: We performed the study using paraffin-embedded tissues of 55 patients who underwent thyroidectomy in Kosin University Gospel Hospital. Of those 55 cases, 36 were papillary thyroid carcinomas, and 19 were benign tumors. Immunohistochemical staining with BMP4 antibody was performed on the paraffin-embedded tissues.Results: Among the 36 papillary thyroid carcinomas, 20 (55.6%) of extrathyroidal invasion and 21 (58.3%) of lymph node metastasis were observed. The presence of calcification was significantly different according to incidence of extranodal invasion (p = 0.02), lymphovascular invasion (p &lt; 0.001), and lymph node metastasis (p = 0.04). BMP-4 expression was weakly positive in benign tumors and strongly positive in papillary thyroid carcinoma (p &lt; 0.001). BMP-4 expression was significantly different by TNM stage (p &lt; 0.001).Conclusion: In the present study, the presence of calcification in thyroid papillary carcinoma was associated with tumor metastasis. BMP-4 was strongly expressed in papillary thyroid carcinoma and was associated with the stage of papillary thyroid carcinoma.