scholarly journals The Independent Prognostic Effect of Lymph Node Dissection on Patients With Stage IA NSCLC With Different T Stages

2021 ◽  
Vol 8 ◽  
Author(s):  
Dechang Zhao ◽  
Rusi Zhang ◽  
Longjun Yang ◽  
Zirui Huang ◽  
Yongbin Lin ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Early Stage ◽  
Rank Test ◽  
Cancer Specific Survival ◽  
Nccn Guidelines ◽  
Prognostic Effect ◽  
Kaplan Meier ◽  
Stage Ia ◽  
Cox Proportional Hazard Regression

Background: Currently, the extent of lymph node evaluation necessary for patients with early-stage non-small-cell lung cancer (NSCLC) remains controversial according to the latest ESMO and NCCN guidelines. In this study, we aimed to evaluate the survival effect of different numbers of lymph nodes examined (LNE) and regions of lymph nodes removed (LNR) in patients with stage IA NSCLC.Method: All patients with stage IA NSCLC undergoing lobectomy or bilobectomy were selected from the surveillance, epidemiology, and end results (SEER) database. The number of LNE and LNR were stratified into 4 groups (0, 1–2, 3–8, and ≥9 lymph nodes) and 3 groups (0, 1–3, and ≥4 regions) respectively. Additionally, the survival curves of overall survival (OS) and cancer-specific survival (CSS) were plotted and compared with the Kaplan-Meier method and log-rank test. Independent prognostic clinicopathological factors were evaluated via Cox proportional hazard regression and subgroup analysis.Results: Totally, 12,490 patients with stage IA NSCLC were enrolled in our study. Patients with ≥9 LNE and ≥4 LNR in both the T1b and T1c stages consistently demonstrated the significantly best OS and CSS outcomes. In the multivariate analysis, patients with ≥9 LNE consistently had a significantly better CSS [hazards ration (HR) (95% CI):0.539 (0.438–0.663)], and those with ≥4 LNR consistently had a significantly better OS [HR (95% CI):0.678 (0.476–0.966)]. Furthermore, ≥9 LNE and ≥4 LNR were associated with better survival in most subgroups.Conclusion: This study demonstrated that ≥9 LNE and ≥4 LNR are highly recommended for stage IA2 and stage IA3 patients but optional for stage IA1 patients.

Outcomes for stage IVA squamous cell carcinoma of the oral cavity according to staging subtypes.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6076-6076
Author(s):  
Kristen Marrone ◽  
Michael Otremba ◽  
Roman Groisberg ◽  
Hari Anant Deshpande ◽  
Forrest Crawford ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Lymph Node ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Rank Test ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Cox Proportional Hazard Regression

6076 Background: Patients with locoregionally advanced squamous cell carcinoma of the oral cavity (SCCOC), defined as stages III to IVB without T4b, are treated similarly and combined for enrollment into most clinical trials. There are several combinations of tumor (T) and lymph node (N) categories for stage IVA. We evaluated the differences in outcomes according to subtypes of patients with stage IVA SCCOC. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients with stage IVA SCCOC diagnosed between 1988 and 2007. Patients were subdivided according to tumor (T) and lymph node (N) status. Overall survival (OS) was estimated by the Kaplan-Meier method and compared by using log-rank test. Cox proportional hazard regression models were used for multivariate analyses. Results: Among the 3,904 patients meeting inclusion criteria, most patients underwent surgery, either alone (24%) or with radiation (59%). There was a significant difference in outcomes according to AJCC subsets (T4aN0, T4aN1, T1N2, T2N2, T3N2 and T4N2), with 5-year OS ranging from 15.8% in T4aN2 to 41.3% in T4aN0 (HR 2.3; 95% CI 2.03-2.62, p < 0.001). Since the 5-year OS was similar for patients with T1N2-T2N2 and T3N2-T4aN2, these groups were further subdivided according to the T (T1-2 or T3-4a) and N2 subsets. The 5-year OS was significantly different according to the subgroups, ranging from 11.8% in T3-4aN2c to 37.5% in T1-2N2a (Table). The stage subgroups remained independent predictors for survival after adjusting for age, gender, race and treatment. Conclusions: Stage IVA SCCOC is a heterogeneous disease with significant differences in outcomes according to its subsets. If these findings are confirmed in additional studies, further subdivision of stage IVA may be warranted. [Table: see text]

Laparoscopic detection of sentinel lymph nodes followed by lymph node dissection in patients with early stage cervical cancer

2003 ◽  
Vol 90 (2) ◽  
pp. 290-296 ◽  
Author(s):  
Marrije R Buist ◽  
Rik J Pijpers ◽  
Arthur van Lingen ◽  
Paul J van Diest ◽  
Jan Dijkstra ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Lymph Node Dissection ◽  
Early Stage ◽  
Sentinel Lymph Nodes ◽  
Node Dissection ◽  
Early Stage Cervical Cancer

scholarly journals CYSTM1: A Novel Biomarker for Hepatocellular Carcinoma Prognosis

2021 ◽  
Author(s):  
Jun Du ◽  
Jinguo Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Early Stage ◽  
Human Tumor ◽  
The Cancer Genome Atlas ◽  
Data Set ◽  
Kaplan Meier ◽  
Cancer Genome Atlas ◽  
Cox Proportional Hazard Regression ◽  
The Relationship

Abstract Background: The expression and molecular mechanism of cysteine rich transmembrane module containing 1 (CYSTM1) in human tumor cells remains unclear. The aim of this study was to determine whether CYSTM1 could be used as a potential prognostic biomarker for hepatocellular carcinoma (HCC).Methods: We first demonstrated the relationship between CYSTM1 expression and HCC in various public databases. Secondly, Kaplan–Meier analysis and Cox proportional hazard regression model were performed to evaluate the relationship between the expression of CYSTM1 and the survival of HCC patients which data was downloaded in the cancer genome atlas (TCGA) database. Finally, we used the expression data of CYSTM1 in TCGA database to predict CYSTM1-related signaling pathways through bioinformatics analysis.Results: The expression level of CYSTM1 in HCC tissues was significantly correlated with T stage (p = 0.039). In addition, Kaplan–Meier analysis showed that the expression of CYSTM1 was significantly associated with poor prognosis in patients with early-stage HCC (p = 0.003). Multivariate analysis indicated that CYSTM1 is a potential predictor of poor prognosis in HCC patients (p = 0.036). The results of biosynthesis analysis demonstrated that the data set of CYSTM1 high expression was mainly enriched in neurodegeneration and oxidative phosphorylation pathways.Conclusion: CYSTM1 is an effective biomarker for the prognosis of patients with early-stage HCC and may play a key role in the occurrence and progression of HCC.

Clinical application of the sentinel lymph node technique in early ovarian cancer: a pilot study

2018 ◽  
Vol 29 (2) ◽  
pp. 377-381 ◽  
Author(s):  
V Lago ◽  
P Bello ◽  
B Montero ◽  
L Matute ◽  
P Padilla-Iserte ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Lymph Node ◽  
Pilot Study ◽  
Sentinel Lymph Node ◽  
Lymph Nodes ◽  
Near Infrared ◽  
Early Stage ◽  
Gamma Probe ◽  
Sentinel Lymph Nodes ◽  
Near Infrared Fluorescence Imaging

IntroductionThere is limited evidence favoring the use of the sentinel lymph node technique in ovarian cancer, and no standardized approach has been studied. The objective of the present pilot study is to determine the feasibility of the sentinel lymph node technique by applying a clinical algorithm.MethodsPatients with confirmed ovarian cancer were included. 99mTc and indocyanine green were injected into the ovarian and infundubulo-pelvic ligament stump. A gamma probe and near-infrared fluorescence imaging were used for sentinel lymph node detection.ResultsThe sentinel lymph node technique was performed in ten patients with a detection rate in the pelvic and/or para-aortic region of 100%. The tracer distribution rates of sentinel lymph nodes in the pelvic and para-aortic regions were 87.5% and 70%, respectively.ConclusionThe detection of sentinel lymph nodes in early-stage ovarian cancer appears to be achievable. Based on these results, a clinical trial entitled SENTOV (SENtinel lymph node Technique in OVarian cancer) will be performed.

scholarly journals Clinicopathological Factors Influencing Lymph Node Yield in Colorectal Cancer: A Retrospective Study

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Elena Orsenigo ◽  
Giulia Gasparini ◽  
Michele Carlucci
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
Rank Test ◽  
Lymph Node Yield ◽  
Log Rank Test ◽  
Lymph Node Retrieval

Many colorectal resections do not meet the minimum of 12 lymph nodes (LNs) recommended by the American Joint Committee on Cancer for accurate staging of colorectal cancer. The aim of this study was to investigate factors affecting the number of the adequate nodal yield in colorectal specimens subject to routine pathological assessment. We have retrospectively analysed the data of 2319 curatively resected colorectal cancer patients in San Raffaele Scientific Institute, Milan, between 1993 and 2017 (1259 colon cancer patients and 675 rectal cancer patients plus 385 rectal cancer patients who underwent neoadjuvant therapy). The factors influencing lymph node retrieval were subjected to uni- and multivariate analyses. Moreover, a survival analysis was carried out to verify the prognostic implications of nodal counts. The mean number of evaluated nodes was 24.08±11.4, 20.34±11.8, and 15.33±9.64 in surgically treated right-sided colon cancer, left-sided colon cancer, and rectal tumors, respectively. More than 12 lymph nodes were reported in surgical specimens in 1094 (86.9%) cases in the colon cohort and in 425 (63%) cases in the rectal cohort, and patients who underwent neoadjuvant chemoradiation were analysed separately. On univariate analysis of the colon cancer group, higher LNs counts were associated with female sex, right colon cancer, emergency surgery, pT3-T4 diseases, higher tumor size, and resected specimen length. On multivariate analysis right colon tumors, larger mean size of tumor, length of specimen, pT3-T4 disease, and female sex were found to significantly affect lymph node retrieval. Colon cancer patients with 12 or more lymph nodes removed had a significantly better long-term survival than those with 11 or fewer nodes (P=0.002, log-rank test). Rectal cancer patients with 12 or more lymph nodes removed approached but did not reach a statistically different survival (P=0.055, log-rank test). Multiple tumor and patients’ factors are associated with lymph node yield, but only the removal of at least 12 lymph nodes will reliably determine lymph node status.

Standard ultrastaging compared to one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node metastases in early stage cervical cancer

2020 ◽  
Vol 30 (12) ◽  
pp. 1871-1877
Author(s):  
Angela Santoro ◽  
Giuseppe Angelico ◽  
Frediano Inzani ◽  
Damiano Arciuolo ◽  
Saveria Spadola ◽  
...  
Keyword(s):  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Lymph Nodes ◽  
Early Stage ◽  
Sentinel Lymph Nodes ◽  
Nucleic Acid Amplification ◽  
Lymph Node Status ◽  
Pelvic Lymph Nodes ◽  
Lymph Node Assessment ◽  
Node Metastases

ObjectiveWe compared ultrastaging and one-step nucleic acid amplification (OSNA) examination of sentinel lymph nodes in two homogeneous patient populations diagnosed with early stage cervical cancer. The primary aim of our study was to evaluate the rate and type of sentinel lymph node metastases detected by ultrastaging and OSNA assay. Secondary aims were to define the sensitivity and the negative predictive value of sentinel lymph node biopsy assessed with OSNA and ultrastaging and to define the role of sentinel lymph node assessment in predicting non-sentinel lymph node status.MethodsConsecutive patients who underwent surgery (radical hysterectomy or trachelectomy or cervical conization) at our institution, between January 2018 and March 2020, were enrolled. All patients had a preoperative diagnosis of early-stage cervical carcinoma (International Federation of Gynecology and Obstetrics (FIGO) 2018 stages IA–IIB) and underwent sentinel lymph node assessment with ultrastaging or OSNA. Patients with advanced FIGO stages and special histology subtypes (other than squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma) or patients with sentinel lymph nodes analyzed only with hematoxylin and eosin were excluded. Clinical data were compared using the χ2 test and Fisher’s exact test. A κ coefficient was determined with respect to lymph node assessment. A p value <0.05 was considered statistically significant.ResultsA total of 116 patients were included in this retrospective analysis (53 ultrastaging, 63 OSNA). Overall, 531 and 605 lymph nodes were removed in the ultrastaging and OSNA groups, respectively, and 140 and 129 sentinel lymph nodes were analyzed in the ultrastaging and OSNA groups, respectively. 22 patients had metastatic sentinel lymph nodes: 6 (11.3%) of 53 patients in the ultrastaging group and 16 (25.4%) of 63 patients in the OSNA group. The total amount of positive SLNs was 7 (5%) of 140 in the ultrastaging group and 21 (16.3%) of 129 in the OSNA group, respectively (p=0.0047). Pelvic lymphadenectomy was performed in 26 (49.1%) of 53 patients in the ultrastaging group and in 34 (54%) of 63 patients in the OSNA group due to comorbidities. Metastatic non-sentinel lymph nodes were found in 4 patients: 2 (7.7%) of 26 patients in the ultrastaging group and 2 (5.9%) of 34 patients in the OSNA group, respectively. The total amount of positive pelvic lymph nodes was 3 (0.6%) of 531 in the ultrastaging group and 4 (0.7%) of 605 in the OSNA group (p=0.61). In the OSNA group, only 2 patients with negative sentinel lymph nodes had metastatic disease in the pelvic lymph nodes. By contrast, no patients with OSNA-positive sentinel lymph nodes had metastases in the pelvic lymph nodes. In the ultrastaging group, all patients with negative sentinel lymph nodes did not have metastatic disease in other pelvic lymph nodes.ConclusionsOSNA assessment of sentinel lymph nodes was associated with a negative predictive value of 91% but poor reliability in detecting node metastases in non-sentinel pelvic lymph nodes. Of note, the ultrastaging protocol revealed higher sensitivity and more reliability in predicting pelvic non-sentinel lymph node status.

Sentinel-node biopsy in early stage ovarian cancer: a prospective multicentre study (SELLY)

2019 ◽  
Vol 29 (9) ◽  
pp. 1437-1439
Author(s):  
Giovanni Scambia ◽  
Camilla Nero ◽  
Stefano Uccella ◽  
Enrico Vizza ◽  
Fabio Ghezzi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Lymph Nodes ◽  
Indocyanine Green ◽  
Epithelial Ovarian Cancer ◽  
Sample Size ◽  
Early Stage ◽  
Sentinel Lymph Nodes ◽  
Exclusion Criteria

BackgroundSystematic para-aortic and bilateral pelvic lymphadenectomy is included in the standard comprehensive surgical staging in presumed early epithelial ovarian cancer. No prospective randomized evidence suggests it has potential therapeutic value, and related morbidity is not negligible.Primary Objective(s)To assess sensitivity, safety, and feasibility of the sentinel lymph node technique in identifying the presence of lymph node metastases in patients with early stage epithelial ovarian cancer.Study HypothesisSentinel lymph node detection with indocyanine green can accurately predict nodal status in a cohort of women with early stage epithelial ovarian cancer.Trial DesignThe SELLY trial is a prospective phase II interventional multicenter study.Major Inclusion/Exclusion CriteriaInclusion criteria: Eastern Cooperative Oncology Group 0–1, apparent International Federation of Gynecology and Obstetrics (FIGO) stage I-II, histologically proven epithelial ovarian cancer.Exclusion criteria: evidence of carcinomatosis, mucinous only at definitive histology.Endpoint(s)Primary endpoint is sensitivity (true positive rate). Secondary endpoints include safety (complications rate of the procedure) and feasibility.Sample SizeAssuming a sensitivity of 98.5% in predicting positive sentinel lymph nodes at histology, a pathological lymph node prevalence of 14.2%, a precision of estimate (ie, the maximum marginal error) d=5%, and a type I error α=0.05, a sample size of 160 patients is needed to test the general hypothesis (ie, to answer whether sentinel lymph nodes identified with indocyanine green can accurately predict nodal status at histology of patients with apparently early epithelial ovarian cancer). Assuming a drop-out rate of 10%, a total of 176 patients will be enrolled in the study.Estimated Dates for Completing Accrual and Presenting ResultsThe accrual should be completed by December 2020 and results should be presented by March 2021.Trial RegistrationThe trial is registered at clinicaltrials.gov (NCT03563781).

Prognostic value of immunohistochemical phenotypes (IP) of 141 operable breast cancer patients (pts) included in phase III trials of adjuvant therapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21040-21040
Author(s):  
R. Trujillo ◽  
E. Gallego ◽  
A. Márquez ◽  
N. Ribelles ◽  
J. Trigo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Regression ◽  
Phase Iii ◽  
Rank Test ◽  
Prognostic Effect ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Phase Iii Trials ◽  
Her 2

21040 Background: Gene expression arrays and IP studies classified breast cancer in three distinct subtypes: basal, HER2/neu and luminal that are associated with different clinical outcomes. Methods: In 141 pts with operable breast cancer, included in phase III trials of adjuvant therapy in our center, immunohistochemical staining was performed on 3μm sections of paraffin blocks, containing tissue-arrays of tumour tissue.A basal phenotype (BP) was defined by negative estrogen receptor (ER) and progesterone receptor (PR) and positive cytokeratin (CK) 5/6 or EGFR immunoreactivity. HER2/neu phenotype as positive c-erb B2 by HercepTest™ and luminal phenotype (LP) by positive ER, PR and CK 7/8 and negative HER-2. Survival curves were calculated by the Kaplan-Meier method. The differences between survivals were estimated using the log rank test. Multivariate Cox regression analysis was used to evaluate any independent prognostic effect of the variables on disease-free survival (DFS). Results: Complete clinical follow-up information was available for 141 pts. The median follow-up period was 52 months (range 1–103 months). During this period, 13.8% pts died from breast cancer and 27.7% pts relapsed. At the time of the primary diagnosis 10.4% of the pts had lymph node negative disease and 89.6% had positive lymph nodes. 50.8% pts received taxane chemotherapy, 7.7% Trastuzumab, 62.3% radiotherapy and 61% pts received hormonotherapy. Positivity for LP was 65.2%, BP 9.9% and Her-2 phenotype 8.5%. 16.3% didn't fit for any of the three subtypes. Median DFS for BP: 24 moths, for LP and Her-2 phenotypes median DFS was not reached. 5 years DFS were; BP: 19%, LP: 63% and Her-2: 56%. Kaplan-Meier survival analyses demonstrated that the presence of a detectable BP was highly significantly associated with a worse DFS compared with the presence of a LP, log rank test (p= 0.0001). Multivariate Cox regression analyses estimated that the prognostic effect of BP in relation to DFS was independent of lymph node, stage and tumor size, HR: 0.12 95% CI (0.05–0.2). Conclusions: We found that expression of BP was associated with poor prognostic in the context of randomized phase III trials. No significant financial relationships to disclose.

Is there a correlation between clinic-pathological features, MSI, PD-L1 and survival outcomes in resected gastric cancer? Looking for optimal biomarkers.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15566-e15566
Author(s):  
Margherita Ratti ◽  
Nicola Valeri ◽  
Jens Claus Hahne ◽  
Andrea Lampis ◽  
Michele Ghidini ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Rank Test ◽  
Survival Outcomes ◽  
Pathological Features ◽  
Chi Square ◽  
Tissue Samples ◽  
Prognostic Effect ◽  
Kaplan Meier ◽  
Chi Square Test ◽  
Msi Analysis

e15566 Background: Identification of prognostic biomarkers for gastric cancer (GC) patient selection is compelling to improve survival outcomes. Microsatellite instability (MSI) is related with a positive prognostic effect in GC, whereas perioperative chemotherapy resulted detrimental in this subgroup. In metastatic GC, immunotherapy with anti-PD1/PD-L1 drugs has shown promising results. Nevertheless, in early stages, data on the relation between MSI, clinic-pathological features, PD-L1 expression and overall survival (OS) remains sparse, especially in Western population. In our study, the prognostic role of MSI, clinic-pathological features and PD-L1 expression in a cohort of Italian GC patients was examined. Methods: CP data of 148 consecutive stage I-III GC pts resected in Cremona Institute between 2010 and 2014 (mostly chemo and/or radio-naive) were collected. MSI analysis was performed on tissue samples for all cases by polymerase chain reaction. PDL-1 expression, evaluated by immunohistochemistry, was assessed in MSI group. Differences between subgroups were evaluated with Chi-square test; Kaplan-Meier method and Long Rank test were used to calculate OS. Results: Female sex (p=0.012), earlier TNM stages (p=0.011) and limited nodal involvement (p=0.29) significantly correlated with MSI status. MSI is significantly associated with better prognosis, exhibiting an advantage of 28.6 months in OS compared with microsatellite stable subgroup (p<0.001). Most MSI patients expressed PD-L1. MSI patients without PD-L1 expression showed higher percentage of clinical features correlated with better prognosis compared with PD-L1 expressing MSI patients and MSS subgroup. Conclusions: MSI is an independent prognostic biomarker in GC and identifies a subset of patients with better OS and specific clinic-pathological features, including high percentage of PD-L1 expression. MSI could represent a promising biomarker to select patients for chemotherapy versus immunotherapy in non-metastatic disease.

scholarly journals Treatment and Survival Analysis for 40-year SEER Data on Upper Esophageal Cancer

2021 ◽  
Author(s):  
Ming-Chuang Zhu ◽  
Guoliang Li ◽  
Peng Xiong ◽  
Min Zhu
Keyword(s):  
Esophageal Cancer ◽  
Neoadjuvant Radiotherapy ◽  
Cancer Specific Survival ◽  
Term Survival ◽  
Regional Stage ◽  
Kaplan Meier ◽  
Seer Data ◽  
Localized Disease ◽  
Regional Disease ◽  
Cox Proportional Hazard Regression

Abstract Background: Upper esophageal cancer (UEC) is rare in western countries. We elucidated the survival outcomes of UEC and analyzed factors associated with prognosis of UEC using the Surveillance, Epidemiology, and End Results (SEER) database.Methods: Cases of UEC (C15.3 and C15.0) arising during the period from 1973 to 2013 were identified and selected. Esophageal cancer-specific survival (ECSS) and overall survival (OS) rate were calculated by Kaplan–Meier method. Cox proportional hazard regression was used to analyze predictive factors.Results: Since 1973, there has been a significant increase (1973-1982 vs. 2004-2013) in median OS (7 months vs. 10 months, p<0.001) and median ECSS (7 months vs. 11months, p < 0.001) among patients with UEC. The ECSS and OS of surgery without radiation (SWR) and radiation plus surgery (R+S) were superior to those of radiation without surgery (RWS). For patients with localized disease, ECSS and OS were highest among patients treated with SWR, compared with patients with R+S and RWS. For patients with regional disease, ECSS and OS were highest among patients with R+S, compared with SWR or RWS. Among patients with regional-stage squamous cell carcinoma (SCC), OS was higher with neoadjuvant radiotherapy or adjuvant radiotherapy, compared with SWR. Multivariate analysis showed that radiotherapy sequence was dependently associated with OS among patients with regional-stage SCC.Conclusion: Although survival of patients with UEC has gradually increased since 1973, the long-term survival among this patient population remains poor. Effective treatments for UEC include surgery, radiotherapy, and combination of surgery and radiotherapy.

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