Node Disease-free Survival Research Articles

Tumor microRNA profile and prognostic value for lymph node metastasis in oral squamous cell carcinoma patients.

Neck lymph node metastasis (LN+) is one of the most significant prognostic factors affecting 1-in-2 patients diagnosed with oral squamous cell carcinoma (OSCC). The different LN outcomes between clinico-pathologically similar primary tumors suggest underlying molecular signatures that could be associated with the risk of nodal disease development. MicroRNAs (miRNAs)are short non-coding molecules that regulate the expression of their target genes to maintain the balance of cellular processes. A plethora of evidence has indicated that aberrantly expressed miRNAs are involved in cancers with either an antitumor or oncogenic role. In this study, we characterized miRNA expression among OSCC fresh-frozen tumors with known outcomes of nodal disease (82 LN+, 76 LN0). We identified 49 differentially expressed miRNAs in tumors of the LN+ group. Using penalized lasso Cox regression, we identified a group of 10 miRNAs of which expression levels were highly associated with nodal-disease free survival. We further reported a 4-miRNA panel (miR-21-5p, miR-107, miR-1247-3p, and miR-181b-3p) with high accuracy in discriminating LN status, suggesting their potential application as prognostic biomarkers for nodal disease.

Abstract 1795: MicroRNA sequence analysis reveals signatures of oral cancer lymph node metastasis

Abstract Regional lymph node metastasis (LN+) at the time of diagnosis or during post-treatment follow-up has devastating impact on the decimal survival of oral cancer (OC) patients. Early intervention on at-risk patient may improve survival. The purpose of the study was to identify microRNA (miRNA) signatures that contribute to LN+ using miRNA sequencing in OC surgical samples. The study comprised a Discovery Cohort (n=91) and a Validation Cohort (n=67) of fresh-frozen primary tumors from 158 patients who were surgically treated between 2005 and 2016 with known outcome of LN (LN+, n=76; LN0, n=82). Total RNA was harvested from >70% tumoral areas. MiRNA-seq libraries were constructed from 2µg total RNA per sample followed by adaptor ligation, reverse transcription, PCR, and sequencing on HiSeq 2000 platform. All analyses were performed using R package (v3.4.4) with input matrix of the miRNAs that expressed at a level of at least 10 reads per million (RPM) in at least 10% of samples. A Least Absolute Shrinkage and Selection Operator (LASSO) penalized regression approach was used to identify miRNAs that would best predict nodal-disease free survival (NFS). Random forest classification analysis was used to rank miRNAs for classifying samples as LN0 and LN+. Among the 158 samples, the LN+ group consisted more poorly differentiated tumors and greater depth of invasion (p=0.0001 and 0.002, respectively). To identify miRNAs that contribute to LN+, we used a penalized regression to generate a signature of NFS. The Discovery Cohort was randomly partitioned into training set (n=72; LN+, n=39, LN0, n=33) to generate a predictive model on NFS. This was then tested in the remaining 19 cases (LN+, n=12, LN0, n=7). The model composed of 2 miRNAs (miR-107 and miR-21-5p) which were significantly overexpressed in LN+. When this was tested in the Validation Cohort (n=67; LN+, 25; LN0, 42), the model was significantly associated with NFS (HR=3.4; 95% CI, 1.5-7.6; 5-year NFS, 24.5%, p=0.001). Additionally, we ranked miRNAs for classifying all samples into LN+ and LN0 by using random forest classification analysis and the two miRNAs from the penalized regression analysis remained to be the top two. The classified LN+ group had significant inferior NFS compared to classified LN0 group (HR=3.2; 95% CI, 2.0-5.1; 5-year NFS, 27.8% vs. 66.7%, p<0.0001). We further investigated diagnostic performance of the two miRNAs using receiver operating curve on all samples which had accuracy of 0.88, sensitivity of 0.82, specificity of 0.80, positive predictive value of 0.82, and negative predictive value of 0.80. In conclusion, our data demonstrated noticeable dysregulated miRNAs that may serve as predictive biomarkers for LN+. Note: This abstract was not presented at the meeting. Citation Format: Kelly Yp Liu, Denise Brooks, Reanne Bowlby, Steve Jones, Catherine F. Poh. MicroRNA sequence analysis reveals signatures of oral cancer lymph node metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1795.

Significance of prophylactic modified radical neck dissection for patients with low-risk papillary thyroid carcinoma measuring 1.1–3.0 cm: First report of a trial at Kuma Hospital

Papillary thyroid carcinoma (PTC) frequently metastasizes to and recurs in regional lymph nodes. Of the two compartments, the central compartment can be dissected through the same wound as the thyroidectomy, and the central node dissection (CND) is routinely performed in most Japanese surgical departments. However, the indications for prophylactic lateral compartment dissection (modified radical neck dissection [MND]) for low-risk PTC remain unclear. In this study, we investigated the indications for prophylactic MND for PTC patients with tumor measuring 1.1-3.0 cm without significant extrathyroid extension or distant metastasis. We investigated the lymph node disease-free survival (LN-DFS) rates of 829 patients who underwent CND and of 414 patients who underwent MND and CND between 2005 and 2007 at Kuma Hospital. The LN-DFS of these two groups was not significantly different. In the subset of patients with CND only, clinical central node metastasis (N1a) significantly predicted a worse LN-DFS. All N1a patients recognized as showing recurrence developed such recurrence in the lateral compartment. Other conventional prognostic factors, such as sex and age, were not related to LN-DFS. Taken together, N1a patients with low-risk PTC measuring 1.1-3.0 cm can be considered as candidates for prophylactic MND.

Sentinel Lymph Node Biopsy in Cutaneous Melanoma: A Case-Control Study

Sentinel lymph node biopsy (SLNB) is the most precise method for staging invasive cutaneous melanoma, but its therapeutic effect has been difficult to assess, and SLNB is not routinely used in all melanoma treatment centers. This case-control study of 305 prospective SLNB patients compared them with 616 retrospective patients who had not undergone invasive nodal staging at diagnosis. Thin melanomas were included in both study groups. A total of 50 SLNB patients were sentinel positive (16.4%) and 255 were sentinel negative (83.6%). A total of 49 of the 50 sentinel-positive patients underwent completion lymph node dissection, and 9 of them (18%) had additional metastases in the nonsentinel nodes. The false-negative rate was 1.6% (five same-basin nodal recurrences during follow-up). There was a significant difference in melanoma-related overall survival (OS) between sentinel-positive and sentinel-negative patients (P < .001). The tumor burden of the sentinel nodes was a significant prognostic factor for melanoma-related OS (P < .001). There was no significant difference in melanoma-related OS or disease-free survival between the study groups, but the nodal disease-free survival was significantly longer among the SLNB patients (P = .004). SLNB is recommended for routine use in the treatment of cutaneous melanoma because the sentinel node status carries unique prognostic information on the survival of melanoma patient. Improved regional disease control is an obvious therapeutic advantage of SLNB and immediate completion lymph node dissection.

Risk Factors for Recurrence to the Lymph Node in Papillary Thyroid Carcinoma Patients without Preoperatively Detectable Lateral Node Metastasis: Validity of Prophylactic Modified Radical Neck Dissection

Although papillary carcinoma usually shows mild characteristics, it metastasizes and shows recurrence to the lymph node in high incidences. Of the two representative lymph node compartments to which papillary carcinoma metastasizes, the central compartment can be routinely dissected via the surgical incision made for thyroidectomy. However, the routine application of prophylactic lateral node dissection (modified radical neck dissection [MND]) remains controversial. In this study, we investigated risk factors for lymph node recurrence of papillary carcinoma to determine the appropriate application of prophylactic MND. We investigated risk factors for lymph node recurrence in 1,231 patients without preoperatively detectable lateral node metastasis who underwent thyroidectomy, central node dissection, and prophylactic MND for papillary carcinoma between 1987 and 1995. The incidence of lateral node metastasis and the number of metastatic lateral nodes significantly increased with carcinoma size. The lymph node disease-free survival (LN-DFS) was also significantly worse in carcinoma with a maximal diameter greater than 3 cm. Massive extrathyroid extension, male gender, and age 55 years or older also reflected a poorer LN-DFS. The 10-year LN-DFS rates of patients with carcinoma having two and three or four of these features were low at 88.5% and 64.7%, respectively, although the rates of those with carcinoma having no or only one characteristic were better than 95%. Prophylactic MND is recommended for cases of papillary carcinoma demonstrating two or more of the following four characteristics; male gender, age 55 years or older, maximal tumor diameter larger than 3 cm, and massive extrathyroid extension.