Delayed Neck Metastasis Research Articles

Identifying factors related to delayed neck metastasis after surgical treatment in patients with oral squamous cell carcinoma

BackgroundGeneral treatment of oral squamous cell carcinoma (OSCC) is surgical treatment with or without neck dissection. Although the incidence of delayed neck metastasis is rare, it may occur after the surgery and is known to be the most important factor in the prognosis. The purpose of is study is to evaluate the clinical and histopathological factors associated with delayed neck metastasis case among patients.MethodsA total of 195 patients who underwent surgical treatment for OSCC from 2016 to 2022 were investigated. Among them, delayed neck metastasis (DNM) was analyzed. The criterion for delayed neck metastasis was a newly developed neck lesion after the primary operation without neck dissection in cN0 necks. To identify the correlation between prognostic factors and the incidence of delayed neck metastasis, χ2 analysis with phi correlation and Cramer’s V test was performed. Cumulative survival rates (CRS) were compared between the groups with the incidence of DNM and without DNM. Also, the log rank test for CSR and Cox proportional hazard model was analyzed to estimate the significance of the CSR and confirm the correlations between prognostic factors and DNM.ResultAmong 195 patients, 14 were discovered to have DNM. The primary tumor locations were the tongue (n = 5), floor of the mouth (n = 2), mandibular gingiva (n = 1), maxillary gingiva (n = 4), retromolartrigone (n = 1), and buccal mucosa (n = 2) each. The cases consisted of TNM stage I (n = 1), stage II (n = 3), stage III (n = 3), and stage IV (n = 8), respectively. The result of the χ2 analysis identified a correlation between positive neck (p = 0.01), depth of invasion (p = 0.09), radiation therapy (p = 0.003), and DNM. Groups without DNM showed better prognosis compared to groups with DNM. Regarding positive neck, depth of invasion, and radiation therapy, only depth of invasion showed significance in CSR analysis.ConclusionDNM after surgical treatment of OSCC is a rare event, and few were found in a review of the literature. Also, many prognostic factors have been suggested but controversial. However, in our study, some prognostic factors have been identified to have a significant correlation with the incidence of DNM, and analysis of such factors provides important information predicting neck metastasis and the prognosis.

Volume-based 18F-fluorodeoxyglucose positron emission tomography/computed tomography parameters correlate with delayed neck metastasis in clinical early-stage oral squamous cell carcinoma.

There is no known preoperative marker that can effectively predict the risk of delayed neck metastasis (DNM), which is an important factor that determines the prognosis of early-stage oral cancer. In this study, we examined whether 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET)/computed tomography (CT) uptake parameters of primary cancer can predict the risk of DNM in early-stage oral squamous cell carcinoma (OSCC). Data from patients with stage I-II OSCC who underwent surgical resection of the primary tumor without elective neck dissection between January 2009 and December 2016 were retrospectively reviewed. Patient characteristics, histopathological factors, and PET/CT parameters (maximum standardized uptake value [SUVmax], metabolic tumor volume [MTV], and total lesion glycolysis [TLG]) were evaluated for their association with DNM. DNM rates were calculated, and the parameters that were statistically significant in the univariate analysis were used as explanatory variables. Independent factors associated with DNM were identified using multivariate analysis. For all statistical analyses, p-values < 0.05 were considered statistically significant. Data from 71 patients were analyzed in the study. The overall DNM rate among all patients was 21.8%. The univariate analysis showed that the T classification, depth of invasion, pattern of invasion, lymphovascular invasion, SUVmax, MTV, and TLG were significant predictors of DNM. However, the multivariate analysis revealed that only the depth of invasion, MTV, and TLG were independent predictors of DNM. This study suggests that, in addition to conventional predictors, volume-based PET parameters are useful predictors of DNM in those with early-stage OSCC.

An examination of the cutoff value of the depth of invasion for prophylactic neck dissection in stage I/II tongue cancer

Background: In stage-I/stage-II oral tongue cancer, the cutoff value of depth of invasion (DOI) for prophylactic neck dissection is controversial.Objectives: To examine the relationship between the DOI and the rate of occult lymph node metastasis. In addition, to examine the relationship between the DOI evaluated by magnetic resonance imaging (MRI) and pathological DOI.Materials and methods: In this retrospective study, 95 patients with clinical T1-2/N0M0 oral tongue cancer were enrolled. The rate of occult lymph node metastasis per DOI between 2 and 11 mm was calculated from the total pathological lymph node metastasis and delayed neck metastasis cases. We measured DOI using MRI and compared DOI obtained from pathology.Results: The total rate of occult lymph node metastasis was 23.9%. In the rate of occult lymph node metastasis per DOI, there were two peaks at point of 5 to 6 mm and 9 to 10 mm. And there was a significant correlation between the DOI evaluated by MRI and the pathological DOI (Pearson’s correlation coefficient was 0.87).Conclusions and significance: There was no consistent increase in the rate of occult lymph node metastasis per DOI. MRI was a useful modality to measure the DOI.

Tumor budding and adjacent tissue at the invasive front correlate with delayed neck metastasis in clinical early-stage tongue squamous cell carcinoma.

Background and ObjectivesSome patients with early‐stage oral cancer have a poor prognosis owing to the delayed neck metastasis (DNM). Tumor budding is reportedly a promising prognostic marker in many cancers. Moreover, the tissue surrounding a tumor is also considered to play a prognostic role. In this study, we evaluated whether tumor budding and adjacent tissue at the invasive front can be potential novel predictors of DNM in early tongue cancer.MethodsIn total, 337 patients with early‐stage tongue squamous cell carcinoma were retrospectively reviewed. The patient characteristics and histopathological factors were evaluated for association with DNM. DNM rates were calculated; items which were significant in the univariate analysis were used as explanatory variables, and independent factors for DNM were identified by the multivariate analysis.ResultsThe univariate analysis identified T classification, depth of invasion, tumor budding, vascular invasion, and adjacent tissue at the invasive front as significant predictors of DNM; the multivariate analysis using these factors revealed all the above variables except vascular invasion, which are independent predictors of DNM.ConclusionIn addition to conventional predictors, high grade tumor budding and adjacent tissue at the invasive front can serve as useful predictors of DNM in early tongue cancer.

Retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy for T2-4N0 tongue cancer: control of occult neck metastasis

To evaluate the therapeutic results and control of occult neck metastasis in patients with T2-4N0 oral tongue squamous cell carcinoma treated with retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy. Forty-two patients with T2-4N0 tongue cancer (17 with late T2; 13 with T3; and 12 with T4a disease, M0) were treated with intra-arterial chemoradiotherapy. Treatment consisted of retrograde superselective intra-arterial chemotherapy (docetaxel 50-70mg/m2, cisplatin 125-175mg/m2) and daily concurrent radiotherapy (50-70Gy) for 5-7weeks. The median follow-up for all patients was 46.5months (range, 8-105months). Primary-site complete response was achieved in 42 of 42 cases (100%). Three-year overall survival, progression-free survival, and local control rates were 85.0%, 77.8%, and 91.7%, respectively. Delayed neck metastasis was detected in 5 of 42 cases (11.9%). Grade 3 or 4 toxic changes included oral mucositis in 92.9%, neutropenia in 21.4%, and thrombocytopenia in 4.8%. Grade 3 toxicities included anemia in 16.7%, radiation dermatitis in 9.5%, nausea in 4.8%, and fever in 2.4%. Retrograde superselective intra-arterial chemotherapy for T2-4N0 tongue cancer provided good overall survival and local control rates and was effective for occult neck metastasis.

舌癌後発頸部転移と鑑別を要したリンパ上皮性嚢胞から発生した扁平上皮癌の1例

舌癌後発頸部転移と鑑別を要したリンパ上皮性嚢胞から発生した扁平上皮癌の1例

Retrospective observational study of occult cervical lymph-node metastasis in T1N0 tongue cancer.

Delayed neck metastasis is the most significant prognostic factor for early tongue cancer. The main strategies for controlling cervical lymph nodes in Japan are elective neck dissection or watchful waiting. Elective neck dissection offers significantly better survival, but adversely impacts patient quality of life; consequently, here we investigated how to identify high-risk patients warranting elective neck dissection. We retrospectively evaluated 67 patients with T1N0 oral tongue squamous cell carcinoma who underwent primary treatment in our department from April 2001 to March 2015. All the patients underwent watchful waiting alone for neck management. We investigated the rates of occult neck metastasis, prognosis and circumstances of recurrence, and associations with pathological tumor thickness, depth and muscle invasion by the primary tumor. Correlation between the thickness in pathological specimens and that at magnetic resonance imaging was additionally investigated. Neck recurrence was evident in 20 patients, of which 19 developed within 1 year. Therefore, the rate of occult neck metastasis was 29.9%. Patients with muscle invasion, tumor thickness ≥2 mm or tumor depth ≥2 mm on surgical specimens were significantly more likely to develop delayed neck metastasis. Prognosis was significantly worse for patients with muscle invasion or tumor thickness ≥2 mm. Thickness using magnetic resonance imaging was well correlated with pathological thickness. Patients with tumors ≥2 mm in thickness or muscle invasion developed neck metastasis, suggesting that elective neck dissection may be warranted for patients with these findings. For preoperative assessment of the need for elective neck dissection, magnetic resonance imaging would be a potential modality for T1N0 tongue cancer.

Abstract 3359: Expression of stem cell markers Oct3/4 and Nanog in the head and neck squamous carcinoma cells and its clinical implications for delayed neck metastasis in stage I/II tongue squamous cell carcinoma

Abstract Background: The side population (SP) of cancer cells is reportedly enriched with cancer stem cells (CSCs), however, the functional role and clinical relevance of CSC marker molecules upregulated in the SP of head and neck squamous carcinoma (HNSCC) cells are yet to be elucidated. Patients with clinical stage I/II (T1-2N0M0) tongue squamous cell carcinoma (TSCC) typically undergo partial glossectomy alone; however, development of delayed neck metastasis (DNM) tends to reduce their survival. In the present study, we aimed to determine the CSC markers in the SP of HNSCC cells along with their functions in cellular behaviors, and to clarify the association of these markers with DNM. Methods: Flow cytometry was applied to isolate SP from main population (MP) in HNSCC cells (SCC4, SAS, and HSC4). The expression of the CSC markers was examined by semi-quantitative RT-PCR and immunocytochemistry. In vitro proliferation, migration, and invasion assays were performed to assess cellular behaviors. Clinicopathological factors and immunohistochemical expressions of Oct3/4 and Nanog were evaluated using surgical specimens from 50 patients with stage I/II TSCC who underwent partial glossectomy alone. Results: SPs were isolated in all three cell lines examined. Expression levels of Oct3/4 and Nanog were higher in SP cells than MP cells. Additionally, cell migration and invasion abilities were higher in SP cells than MP cells, whereas there was no difference in proliferation. Univariate analysis showed that expression of Oct3/4 and Nanog, vascular invasion, muscular invasion, and mode of invasion were significantly correlated with DNM. Multivariate logistic regression revealed that Oct3/4 expression (risk ratio = 14.78, p = 0.002) and vascular invasion (risk ratio = 12.93, p = 0.017) were independently predictive of DNM. Regarding the diagnostic performance, Oct3/4 showed the highest accuracy, sensitivity, and negative predictive value of 82.0%, 61.5%, and 86.8%, respectively, while vascular invasion showed the highest specificity and positive predictive value of 94.6% and 71.4%, respectively. Conclusion: These results suggest that Oct3/4 and Nanog represent probable CSC markers in HNSCC, which contribute to the development of DNM in part by enhancing cell motility and invasiveness. Moreover, along with vascular invasion, expression of Oct3/4 in the primary cancer cells can be considered a potential predictor for selecting patients at high risk of developing DNM. Citation Format: Noboru Habu, Yorihisa Imanishi, Kaori Kameyama, Masayuki Shimoda, Yutaka Tokumaru, Koji Sakamoto, Ryoichi Fujii, Seiji Shigetomi, Kuninori Otsuka, Yoichiro Sato, Yoshihiro Watanabe, Hiroyuki Ozawa, Toshiki Tomita, Masato Fujii, Kaoru Ogawa. Expression of stem cell markers Oct3/4 and Nanog in the head and neck squamous carcinoma cells and its clinical implications for delayed neck metastasis in stage I/II tongue squamous cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3359.

Sentinel lymph node biopsy reduces the incidence of secondary neck metastasis in patients with oral squamous cell carcinoma.

It has recently been established that sentinel node biopsy (SNB) is an applicable and feasible procedure for the prediction of neck lymph node status in patients with early oral squamous cell carcinoma (OSCC) who are clinically negative for neck metastasis (cN0). The aim of this study was to retrospectively compare excision followed by watchful waiting with excision and SNB, in order to determine the effectiveness of SNB. A total of 125 patients with cN0 early OSCC were divided into two groups, namely the excision alone (n=78) and excision with SNB (n=47) groups. The clinical data of these two groups between 2006 and 2013 were analyzed. In the excision with SNB group, the negative predictive value and false-negative rate of SNB were 94% (30/32) and 18% (2/11), respectively. Secondary neck metastasis, also known as delayed neck metastasis, occurred in 24.2% of the patients in the excision alone group and 4.9% of the patients in the excision with SNB group. The 5-year overall survival (OS) rates were 84.0 and 97.5% in the excision alone and excision with SNB groups, respectively. Significant differences were found in the rate of secondary neck metastasis and OS between the two groups. SNB may be effective in the detection of occult neck lymph node metastasis, with a reduction in the incidence of secondary neck metastasis and improvements in the 5-year OS in patients with early-stage (stage I/II) oral cancer.

Expression of Oct3/4 and Nanog in the head and neck squamous carcinoma cells and its clinical implications for delayed neck metastasis in stage I/II oral tongue squamous cell carcinoma.

BackgroundThe side population (SP) of cancer cells is reportedly enriched with cancer stem cells (CSCs), however, the functional role and clinical relevance of CSC marker molecules upregulated in the SP of head and neck squamous carcinoma (HNSCC) cells are yet to be elucidated. Patients with clinical stage I/II (T1-2N0M0) tongue squamous cell carcinoma (TSCC) typically undergo partial glossectomy; however, development of delayed neck metastasis (DNM) tends to reduce their survival. In the present study, we aimed to determine the CSC markers in the SP of HNSCC cells along with their functions in cellular behaviors, and to clarify the association of these markers with DNM.MethodsFlow cytometry was applied to isolate SP from main population (MP) in HNSCC cells. The expression of the CSC markers was examined by semi-quantitative RT-PCR and immunocytochemistry. In vitro proliferation, migration, and invasion assays were performed to assess cellular behaviors. Clinicopathological factors and immunohistochemical expressions of Oct3/4 and Nanog were evaluated using surgical specimens from 50 patients with stage I/II TSCC.ResultsSPs were isolated in all three cell lines examined. Expression levels of Oct3/4 and Nanog were higher in SP cells than MP cells. Additionally, cell migration and invasion abilities were higher in SP cells than MP cells, whereas there was no difference in proliferation. Univariate analysis showed that expression of Oct3/4 and Nanog, vascular and muscular invasion, and mode of invasion were significantly correlated with DNM. Multivariate logistic regression revealed that Oct3/4 expression (risk ratio = 14.78, p = 0.002) and vascular invasion (risk ratio = 12.93, p = 0.017) were independently predictive of DNM. Regarding the diagnostic performance, Oct3/4 showed the highest accuracy, sensitivity, and NPV of 82.0 %, 61.5 %, and 86.8 %, respectively, while vascular invasion showed the highest specificity and PPV of 94.6 % and 71.4 %, respectively.ConclusionThese results suggest that Oct3/4 and Nanog represent probable CSC markers in HNSCC, which contribute to the development of DNM in part by enhancing cell motility and invasiveness. Moreover, along with vascular invasion, expression of Oct3/4 can be considered a potential predictor for selecting patients at high risk of developing DNM.

Overexpression of SIP1 and Downregulation of E-cadherin Predict Delayed Neck Metastasis in Stage I/II Oral Tongue Squamous Cell Carcinoma After Partial Glossectomy

Patients with clinical stage I/II (T1-2N0M0) oral tongue squamous cell carcinoma (TSCC) usually undergo partial glossectomy alone. However, 14-48% of them develop delayed neck metastasis (DNM), which may lead to an unfavorable course. Recently epithelial-to-mesenchymal transition (EMT) has been thought to play a crucial role in cancer metastasis. The present study aimed to examine the associations of EMT-involved molecular factors and clinicopathological factors with DNM in stage I/II TSCC. mRNA expression levels of E-cadherin and its transcriptional repressors (snail, SIP1, and twist) in 7 head and neck squamous cell carcinoma (HNSCC) cell lines were evaluated by quantitative real-time PCR. Clinicopathological parameters and immunohistochemical expressions of E-cadherin and its repressors were examined in surgical specimens of 37 stage I/II TSCC patients who underwent partial glossectomy alone. In HNSCC cells, E-cadherin expression was inversely correlated with SIP1 expression (P = 0.023). Univariate analysis of immunohistochemistry showed that overexpression of SIP1 and loss of E-cadherin were significantly correlated with DNM, although no inverse correlation was found between E-cadherin and its repressors. Multiple logistic regression analysis including clinicopathological and molecular factors revealed that overexpression of SIP1 (P = 0.005), loss of E-cadherin (P = 0.046), and vascular invasion (P = 0.024) were independently correlated with DNM. These results suggest that development of DNM in stage I/II TSCC is closely related to induction of EMT in primary tumor cells. Especially, SIP1 and E-cadherin are considered to be the possible markers for selecting patients at high risk of DNM.

Secretory Leukocyte Protease Inhibitor (SLPI) Expression and Tumor Invasion in Oral Squamous Cell Carcinoma

Differential expression of secretory leukocyte protease inhibitor (SLPI) impacts on tumor progression. SLPI directly inhibits elastase and other serine proteases, and regulates matrix metalloproteinases, plasminogen activation, and plasmin downstream targets to influence invasion. We examined tissues from human oral squamous cell carcinoma (OSCC) for SLPI expression in parallel with proteases associated with tumor progression and evaluated their relationships using tumor cell lines. Significantly decreased SLPI was detected in OSCC compared to normal oral epithelium. Furthermore, an inverse correlation between SLPI and histological parameters associated with tumor progression, including stage of invasion, pattern of invasion, invasive cell grade, and composite histological tumor score was evident. Conversely, elevated plasmin and elastase were positively correlated with histological parameters of tumor invasion. In addition to its known inhibition of elastase, we identify SLPI as a novel inhibitor of plasminogen activation through its interaction with annexin A2 with concomitant reduced plasmin generation by macrophages and OSCC cell lines. In an in vitro assay measuring invasive activity, SLPI blocked protease-dependent tumor cell migration. Our data suggest that SLPI may possess antitumorigenic activity by virtue of its ability to interfere with multiple requisite proteolytic steps underlying tumor cell invasion and may provide insight into potential stratification of oral cancer according to risk of occult metastasis, guiding treatment strategies.

Abstract 5213: Overexpression of SIP1 and down-regulation of E-cadherin predict delayed neck metastasis in stage I/II oral tongue squamous cell carcinoma after partial glossectomy

Abstract Neck lymph node involvement is considered as the most important adverse prognostic factor in head and neck squamous cell carcinoma (HNSCC). Patients with clinical stage I/II (T1-2N0M0) oral tongue carcinoma usually undergo partial glossectomy alone. However, 14 to 48% of these patients develop delayed neck metastasis (DNM) within 2 years and tend to result in unfavorable course. Clinicopathologic features and molecular biomarkers have been investigated to find the reliable predictor of DNM, however, it still remains to be elucidated. Recently E-cadherin and its transcriptional repressors are thought to play a crucial role in tumor progression and metastasis, the mechanism of which is called epithelial to mesenchymal transition (EMT). The present study was aimed to examine whether the molecular factors involved in the induction of EMT, as well as standard clinicopathologic factors, are predictive of DNM in stage I/II oral tongue squamous cell carcinoma. mRNA expressions of E-cadherin and its repressors (snail, SIP1 and twist) in 7 HNSCC cell lines were evaluated by quantitative real-time RT-PCR, which revealed significant inverse correlation between E-cadherin and SIP1 (p = 0.023). Immunohistochemical staining was performed to evaluate protein expressions of E-cadherin and its repressors in the specimens of the primary lesions of 37 stage I/II tongue carcinoma patients who had initially undergone only partial glossectomy in the Keio University Hospital without elective neck dissection. Univariate analysis showed that loss of E-cadherin (p = 0.004) and overexpression of SIP1 (p &amp;lt; 0.001) were significantly correlated with DNM, although no inverse correlation was found between E-cadherin and each of its repressors. Regarding other clinicopathologic factors, mode of invasion 3/4 (p = 0.048), vascular invasion (p = 0.021) and muscular invasion (p = 0,012) were also significantly correlated with DNM. Multiple logistic regression analysis including clinicopathologic and the molecular factors elucidated that overexpression of SIP1 (p = 0.005), loss of E-cadherin (p = 0.046) and vascular invasion (p = 0.024) were independently correlated with DNM. These results suggest that DNM in the stage I/II oral tongue carcinoma is closely relating to EMT, and especially SIP1 and E-cadherin are considered as the useful markers to predict development of DNM. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5213. doi:10.1158/1538-7445.AM2011-5213

Histopathological and Lymphangiogenic Parameters in Relation to Lymph Node Metastasis in Early Stage Oral Squamous Cell Carcinoma

Lymph node metastasis from oral squamous cell carcinoma (SCC) correlates with a poor prognosis. Therefore, accurate assessment of lymph node status is crucial in treatment planning. Furthermore, prediction of delayed neck metastasis (DNM), especially in early stage tumors with a clinically negative (N0) neck, will determine the need for neck dissection or irradiation. In this study, we assess various clinical, histopathological and lymphangiogenic parameters in early stage oral SCC and their association with DNM. Clinical, histological, and immunohistochemical analyses were undertaken for 29 patients with T1N0M0 or T2N0M0 oral SCC affecting the tongue or floor of mouth and correlated with the development of DNM. Tumor thickness, nuclear pleomorphism, pattern of invasion, and immunohistochemical expression of the lymphangiogenesis-associated molecules VEGFR-3 and VEGF-C were associated with DNM. Analysis of these parameters may help to identify patients who would benefit from a neck dissection or irradiation by predicting the likelihood of lymph node metastasis.

PD.205 Predictive factors for initial and delayedneck metastasis in patients with lip squamous cell carcinoma

PD.205 Predictive factors for initial and delayedneck metastasis in patients with lip squamous cell carcinoma

Squamous Cell Carcinoma of the Lower Lip and Supra-Omohyoid Neck Dissection

Purpose: The aim of this study is to evaluate our approach to patients with squamous cell carcinoma of lower lip.Patients and methods: This study includes 31 lower lip squamous cell carcinomas followed up between 1994 and 2000. Primary treatment was applied to 28 patients of whom 23 were in stages I-II and five in stages III-IV. Three patients presented locoregional recurrence. Neck dissection was performed during primary lip resection in patients with palpable cervical lymph node involvement. Patients with unpalpable cervical lymph nodes were divided into two subgroups: one was submitted to elective neck dissection (n = 11) and the other had isolated lip resection (n = 8). Unilateral or bilateral selective supra-omohyoid neck dissection (SOHND) was performed according to the localisation of the disease. Radical dissection was performed in a secondary intervention, when SOHND revealed lymph node metastases. Radiotherapy and chemotherapy were applied for curative and/or adjuvant treatment in addition to surgery in patients with locoregional recurrence and metastatic lymph nodes or with perineural involvement.Results: Occult cervical metastasis within a single lymph node was found in one of the 11 No patients who underwent elective neck dissection. Delayed neck metastasis developed in one of the eight patients in whom isolated lip resection (without neck exploration) was performed. Chemoradiotherapy was administered to this patient, but he died. Neck metastasis was established histologically in four of five patients in stages III-IV. Postoperative radiotherapy was used on these patients. One of the patients in this group died due to inoperable local recurrence in the neck, another died because of distant metastasis. Local mandibular recurrence was seen in one of these patients after three years. Comment: Six patients (19%) died due to lower lip carcinoma in this series. Our findings show the importance of elective neck dissection and intact surgical resection margins.

Prediction of delayed neck metastasis in patients with stage I/II squamous cell carcinoma of the tongue.

The incidence of delayed neck metastasis (DNM) in patients with squamous cell carcinoma (SCC) of the tongue is reported to be 20% to 50%. Although clinically negative cervical lymph nodes (N0) are associated with a good outcome, the prognosis is poor in patients with DNM. The aim of this study was to evaluate the clinicopathological and immunohistochemical parameters associated with DNM in patients with stage I/II SCC. Fifty nine patients, with previously untreated stage I/II carcinoma, underwent examination of clinicopathological and immunohistochemical parameters and incidence of DNM. A linear discriminant analysis was used to analyze prognostic factors and to determine the probability of DNM occurring. DNM occurred in 14 (24%) subjects of the 59 study patients, level I to level III, within 5 years. Parameters such as gender and age, disease stage, tumor size and histological grade, tumor location, degree of tumor invasion and expression of VEGF, E-cadherin or Ki-67 showed no significant correlation with the occurrence of DNM; however, factors such as tumor morphology, tumor thickness greater than 4 mm, and Flt-4 expression were significantly associated with development of DNM. Such factors provide useful information with regard to DNM and the prognosis. We concluded that patients with early SCC whose tumors are > 4 mm in thickness and immunopositive for Flt-4 are particularly at risk of developing DNM.

Radiation therapy for glottic cancer using 6-MV photons

It has been recommended that cobalt-60 or 4-MV photons be used when treating glottic cancer with radiation therapy. Underdosing may occur when using higher energy photons, particularly when the anterior commissure is involved. The authors report their experience using higher energy photons (6 MV) for the treatment of glottic cancer. Between January 1975 and July 1991, 73 patients with Tis, T1, T2, or T3 glottic tumors underwent radiation therapy with curative intent. Cobalt-60 or 4-MV photons were used to treat the cancers of 30 patients, and 6-MV photons were used to treat 43 patients. Clinical records were reviewed retrospectively to determine patterns of treatment failure, cancer deaths, and local tumor control in the 43 patients receiving treatment with 6-MV photons. Patients were followed until death or for a minimum of two years. Treatment failures were: local recurrence, one patient; local recurrence and distant metastasis, one patient; delayed neck metastasis, two patients; and delayed neck metastasis with distant metastasis, one patient. Three patients who had treatment failure are alive and free of cancer after salvage treatment. Two patients died of neck and distant metastases. The 2-year initial local tumor control rate was 94.8%. Glottic cancer can be treated successfully with 6-MV photons. Local tumor control is similar to that reported using cobalt-60 or 4-MV photons.

Patterns of failure after total laryngectomy for glottic carcinoma.

The 136 patients who underwent total laryngectomy as the primary treatment for squamous cell carcinoma of the glottis at the Mayo Clinic in 1970 through 1981 were followed by retrospective record review for at least 4 years or until death, local recurrence, neck recurrence, or delayed neck metastasis. Cancer recurred or progressed in a previously untreated area in 35 patients; for the 29 affected above the clavicles, the median time to manifestation was 9.9 months. A Cox model with four risk factors (P less than 0.05) was found to predict failure above the clavicles: lymph node metastasis in the laryngectomy specimen (Delphian, pretracheal, tracheoesophageal, parathyroid), primary tumor more than 1.5 cm in greatest diameter, subglottic extension, and lymph node metastasis in the neck dissection specimen. A simple risk score computed from the Cox model shows that the more factors present, the higher the risk of disease progression or recurrence.