Point-of-care ultrasound in the head and neck region.

Point-of-care ultrasound (POCUS) in the head and neck region plays a particularly significant role in the diagnosis and treatment of upper airway stenosis, swelling, and painful diseases in the neck, and in the evaluation of swallowing function. Therefore, it should be performed in various medical settings beyond the boundaries of the clinical department such as general medicine, emergency medicine, anesthesiology, orthopedics, and pediatrics. The target diseases are salivary gland disease, lymph node disease, pharyngeal disease, laryngeal disease, esophageal disease, thyroid disease, and dysphagia and dyspnea due to various causes. Head and neck POCUS is an extremely useful diagnostic method for both patients and doctors, and its use is expected to become more widespread in the future.

Comparison of Clinical Outcomes of Definitive and Postoperative Radiotherapy for Adenoid Cystic Carcinoma of the Head and Neck: Can Definitive Radiotherapy Be a Treatment Option?

BACKGROUND: The standard treatment for adenoid cystic carcinoma of the head and neck is surgical resection followed by postoperative radiotherapy (PORT). Currently, definitive radiotherapy (defRT) is considered an inadequate treatment; however, its data are based on studies using classical radiotherapy techniques. Therefore, the therapeutic effects of current radiotherapy techniques have not been adequately evaluated, and it may have underestimated the efficacy of defRT. METHODS: We retrospectively analyzed 44 adenoid cystic carcinoma patients treated with radiotherapy based on modern treatment techniques from 1993 to 2017. RESULTS: Twenty-four patients underwent PORT and 20 patients underwent defRT. The 5-year overall survival rates for patients treated with PORT and defRT were 85.3% and 79.7%, respectively. The 5-year local control rates were 82.5% and 83.1%, respectively. There were no statistically significant differences in the overall survival and local control of patients treated with PORT and defRT (p = 0.4392 and p = 0.0904, respectively). CONCLUSION: Our results show that defRT is comparable to surgical resection followed by PORT with respect to overall survival and local control. The results suggest that defRT can be an effective treatment option for adenoid cystic carcinoma of the head and neck.

Prognostic Role of Tumor-Infiltrating Lymphocytes and Tumor Budding in Early Oral Tongue Carcinoma.

OBJECTIVES/HYPOTHESIS: Occult lymph metastasis is an important prognosticator for the treatment of early oral tongue squamous cell carcinoma (SCC). The objective of this study was to evaluate the prognostic significance of tumor-infiltrating lymphocytes (TILs) in early oral tongue SCC. The combination of the TIL subtype and intermediate- or high-grade budding scores was investigated as a prognostic marker for occult neck metastases. STUDY DESIGN: Retrospective study. METHODS: Specimens from 62 patients with early oral tongue SCC treated with only primary surgery were analyzed by immunohistochemistry for CD4+, CD8+, FoxP3+, and CD45RO+ T cells and CD163+ macrophages. The highest number of each TIL subtype was counted in two areas of parenchyma and stroma in the tumor (Tumor) and peripheral stroma of the invasion margin. RESULTS: Based on multivariate analysis, a high density of Tumor CD163+ macrophages served as the poorest prognostic factor for regional control (RC) and disease-free survival (DFS). Patients with both a high density of Tumor CD163+ macrophages and an intermediate- or a high-grade budding score had a poor prognosis for RC according to the log-rank test. CONCLUSIONS: In summary, each TIL subtype may use different mechanisms during early and advanced stages of oral tongue SCC. A high density of Tumor CD163+ macrophages was determined to be a risk factor for RC and DFS as well as an additional stratification factor for RC in patients with intermediate- or high-grade budding scores. Therefore, identifying TIL subtypes in daily clinical practice can help determine a more successful and individualized therapeutic approach for early oral tongue SCC. LEVEL OF EVIDENCE: Step 4 (Level 4) Laryngoscope, 131:2512-2518, 2021.

The Utility of Ultrasonography in the Diagnosis of Cervical Lymph Nodes after Chemoradiotherapy for Head and Neck Squamous Cell Carcinoma.

Background and Objectives: There is evidence or consensus on the use of 18F-2-fluorodeoxyglucose-positron emission tomography with computed tomography (PET-CT) in evaluating the effects of treatment at 12 weeks after chemoradiotherapy for head and neck squamous cell carcinoma with cervical lymph node metastasis. However, the use of imaging to evaluate the effects of treatment within 12 weeks after chemoradiotherapy is controversial. The aim of this study was to evaluate the usefulness of ultrasonography in the diagnosis of lymph nodes metastasis after chemoradiotherapy according to the criteria of the "Evaluation of the effects of treatment on metastatic cervical lymph nodes using ultrasonography", which evaluated lymph nodes metastasis based on size change and presence of degeneration. Materials and methods: This prospective study included 34 head and neck squamous cell carcinoma patients with cervical lymph nodes metastasis. Thirty-two patients who completed treatment were analyzed. Ultrasonography was performed at 4 and 8 weeks after chemoradiotherapy and we judged whether a favorable prognosis could be expected or whether additional treatments should be considered. Ultrasonography and PET-CT were performed at 12 weeks after chemoradiotherapy. Neck dissection was performed if residual disease was suspected based on the PET-CT findings. Results: The accuracy and negative predictive value of ultrasonography were 81.3% and 96.3%, respectively. According to the Ultrasonography findings, the size of lymph nodes metastasis after chemoradiotherapy was significantly smaller than those before chemoradiotherapy (p < 0.05). The fluid and blood flow of lymph nodes metastasis showed a significantly reduced at 12 weeks after chemoradiotherapy (p < 0.05, p < 0.05, respectively). The echo density significantly changed from low to high echoic density after chemoradiotherapy (p < 0.05). Conclusions: Ultrasonography was useful for evaluating cervical lymph nodes metastasis after chemoradiotherapy for head and neck squamous cell carcinoma.

Association between pathological invasion patterns and late lymph node metastases in patients with surgically treated clinical No early oral tongue carcinoma.

BACKGROUND: This study evaluated the combination of tumor budding and depth (BD model) and worst pattern of invasion (WPOI) as histopathological prognostic factors in clinical N0 early oral tongue carcinoma. METHODS: Data from 62 patients were retrospectively analyzed. Associations between histopathological factors (differentiation, stage, lymphatic invasion, blood vessel invasion, WPOI, and BD model) and regional control (RC) or disease-free survival (DFS) were evaluated. RESULTS: The five-year RC and DFS rates were 74% and 65%, respectively. Univariate analysis identified blood vessel invasion, lymphatic invasion, WPOI, and BD model, whereas multivariate analysis identified WPOI, and BD model, as predictive factors for RC. Univariate analysis identified lymphatic invasion, WPOI, and BD model, whereas multivariate analysis identified WPOI, as predictive factors for DFS. CONCLUSION: The pathological invasion patterns should be considered when determining the follow-up plan for patients with clinical N0 early oral tongue carcinoma.

Diagnosis of cervical lymph node metastases in head and neck cancer with ultrasonic measurement of lymph node volume.

OBJECTIVE: The purpose of this study was to evaluate the usefulness of ultrasound (US) volume measurement of the cervical lymph nodes for diagnosing nodal metastasis in patients with head and neck cancer using a node-by-node comparison. METHODS: Thirty-four consecutive patients with head and neck cancer from one tertiary university hospital were prospectively enrolled from 2012 to 2017. Patients with histologically proven squamous cell primary tumors in the head and neck region scheduled to undergo a therapeutic neck dissection were eligible. For each patient, 1-4 target lymph nodes were selected from the planned neck dissection levels. Lymph nodes with thickness >20 mm or in a cluster were excluded. Node-by-node comparisons between the pre-operative US assessment, the post-operative actual measurements and histopathological results were performed for all target lymph nodes. Quantitative measurements, such as three diameters, ratios of the three diameters and volume were analyzed in this study. Lymph node volume was calculated using the ellipsoid formula. RESULTS: Patients comprised 28 men and 6 women with a mean age of 60.0 years (range, 29-80 years) at the time of surgery. In total, 67 target lymph nodes were analyzed in this study and the thickness ranged from 3.9 to 20.0 mm (mean 8.0 mm). There was a strong correlation between the US volume and post-operative actual volume (ρ = 0.87, p < 0.01). The US volume measured 2156 ± 2156 mm3 for the tumor positive nodes, which was significantly greater than the US volume of 512 ± 315 mm3 for tumor negative nodes (p < 0.01). Significant differences between tumor positive and tumor negative nodes were found in five variables (volume, thickness, major axis, minor axis and ratio of minor axis to thickness) for total lymph nodes. To identify predictors of lymph node metastasis, ROC curves of the US variables of target lymph nodes were compared, of which 4 variables were considered acceptable for predicting the lymph node metastasis: volume (AUC 0.86), thickness (AUC 0.86), major axis (AUC 0.79), and minor axis (AUC 0.79) for total lymph nodes. The optimal cut-off level for US volume in total lymph nodes was found to be 1242 mm3, whereby a 62% sensitivity and 98% specificity was reached (likelihood ratio: 25.2). CONCLUSION: Pre-operative ultrasonic volume measurement of the cervical lymph nodes was useful for early detection of cervical nodal metastasis in head and neck cancer.

Impact of combined modality treatment with radiotherapy and S-1 on T2N0 laryngeal cancer: Possible improvement in survival through the prevention of second primary cancer and distant metastasis.

BACKGROUND: In patients with head and neck cancer, the management of second primary cancer (SPC) is particularly important for improving survival because of its high incidence and associated mortality. We evaluated the impact of combination chemotherapy on survival and SPC. METHOD: We retrospectively analyzed data from 49 patients treated with definitive radiation therapy (RT) for T2N0M0 laryngeal squamous cell carcinoma between 2003 and 2011. Among them, 22 patients received combined modality treatment with radiotherapy and S-1 (RT+CT group). RESULTS: The median follow-up period was 71months (32-111months). A significant difference in overall survival (OS, P<0.01) was observed between the RT+CT group (n=22) and the RT alone group (n=27) though no significant differences were observed in local control and disease specific survival. Univariate analyses showed that an older age (P<0.05) and a higher grade (P<0.05) were associated with OS. Multivariate analysis identified chemotherapy as the most significant predictor of survival (OR, 0.056; 95% CI, 0.008-0.353, P<0.01). A significantly lower incidence of distant metastasis (DM)+SPC (5-year incidence: 5% vs. 19%, P<0.05) and fewer deaths from these causes (1 vs. 8: P<0.05) were observed in the RT+CT group. Multivariate analysis showed that chemotherapy was the most significant factor for the incidence of DM+SPC (OR, 0.074; 95% CI, 0.0065-0.84; P<0.05). CONCLUSION: The findings of this study suggest the possibility that combined modality treatment with radiotherapy and S-1 improve survival by preventing distant metastasis and second primary cancer.

Predictive Significance of Tumor Depth and Budding for Late Lymph Node Metastases in Patients with Clinical N0 Early Oral Tongue Carcinoma.

In clinical N0 early oral tongue carcinoma, treatment of occult lymph node metastasis is controversial. The purpose of this study was to assess the histopathological risk factors for predicting late lymph node metastasis in early oral tongue carcinoma. We retrospectively reviewed 48 patients with early oral tongue squamous cell carcinoma. Associations between the histopathological factors (depth of tumor, differentiation, blood vessel invasion, lymphatic invasion, and tumor budding) and late lymph metastasis were analyzed. Although the univariate analysis identified blood vessel invasion, lymphatic invasion, and high-grade tumor budding as predictive factors for neck recurrence (p < 0.001), the Cox proportional hazards model identified high-grade tumor budding as an independent predictive factor (p < 0.01). The combination of a tumor depth ≥ 3 mm and high-grade tumor budding yielded high diagnostic accuracy. Tumor depth and budding grade were identified as histopathological risk factors for late neck recurrence in clinical N0 early oral tongue carcinoma.

Suspected Aerogenous Lung Metastases From Nasopharyngeal Cancer.

A 44-year-old man experiencing repeated episodes of epistaxis and respiratory aspiration was diagnosed with nasopharyngeal cancer. Although the tumor completely disappeared after chemoradiation, six pulmonary nodules developed in the right lower lobe within a year. Right lower lobectomy was performed. All nodules were metastases of the nasopharyngeal cancer. Surgery was performed despite a poor prognosis, and there has been no recurrence 12 years postoperatively. Aerogenous metastases were suggested owing to right lower lobe localization and the patient's symptoms and prolonged survival. The possibility of aerogenous spread and the efficacy of local therapy should be further studied.

Primary definitive radiotherapy with or without chemotherapy for squamous cell carcinoma of the temporal bone.

We aimed to evaluate the impact of concurrent chemoradiotherapy (CCRT) on the survival of patients with squamous cell carcinoma of the temporal bone. We retrospectively analyzed the data of 13 consecutive patients who were treated by definitive radiation therapy (RT) or CCRT as the initial treatment between 1999 and 2012. There were 5 patients with stage II disease, 5 with stage III, and 3 with stage IV, as classified according to the University of Pittsburgh system. Among these, 2, 4, and 3 patients, respectively, were treated by CCRT; whereas the remaining (3 patients with stage II and 1 with stage III) were treated by RT alone. Median follow-up duration was 39 months (12-106 months) in all cases, and 61.5 months (17-70 months) in censored cases. The 5-year overall survival (OS) rates were 51 % in all patients, and 40, 100, and 0 % in patients with stage II, stage III, and stage IV disease, respectively. In patients with stage II and III disease, the 5-year OS rates were 80 % in the CCRT group and 50 % in the RT-alone group. We found better prognosis in patients with stage II and III disease who were treated by CCRT. Only 2 patients treated by CCRT experienced adverse events more than grade 3, which were neutropenia and dermatitis. There was no late adverse event of bony necrosis. Our study results indicate that CCRT is safe and very effective as a first-line treatment for stage II and III squamous cell carcinoma of the temporal bone.

Prognostic factors for local control in patients receiving radiation therapy for early glottic cancer: anterior commissure involvement and effect of chemoradiotherapy.

To assess the prognostic factors for local control in patients with early glottic cancer, we retrospectively analyzed the data of 130 consecutive patients who were treated by definitive radiation therapy (RT) or concurrent chemoradiotherapy (CRT) for early glottic squamous cell carcinoma (UICC sixth edition T1N0M0 and T2N0M0) at Kanagawa cancer center between 1999 and 2011. There were 63 patients with T1 cancer and 67 patients with T2 cancer. Twenty-one patients with T2 tumors were treated by chemoradiotherapy (CRT). The median follow-up period was 73 months (range, 22-165 months). The 5-year local control (LC) rate in all patients was 81 %. The 5-year LC rates in the patients with T1 and T2 cancer were 89 and 74 %, respectively. Univariate analysis showed that a higher T stage (T2) (p = 0.0301), anterior commissure involvement (p < 0.000001), and habitual drinking (p = 0.054) were correlated with decreased local control rate. Multivariate analysis identified only anterior commissure involvement as a significant prognostic factor for local control (LC rate 91 vs. 51 %, risk ratio 5.3, 95 % CI 2.3-12, p < 0.001). In the patients with T2 cancer, there was no statistically significant difference in the LC rate between patients who received RT alone and those who received CRT (RT alone 76 % vs. CRT 67 %; p = 0.832). The findings of this study suggest that anterior commissure involvement is a significant factor influencing the prospect of local control. CRT was not found to be effective for T2 patients in this study.

Definitive radiotherapy for early-stage hypopharyngeal squamous cell carcinoma.

The present study analyzed the outcomes of patients with early-stage hypopharyngeal squamous cell carcinoma (HPSCC) treated with radical radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). We retrospectively reviewed the clinical records of 33 patients with early-stage HPSCC who underwent RT or CCRT between January 1999 and December 2011. Of the 33 patients who were treated, 12 had Stage I and 21 had Stage II disease. Patients with Stage I were typically treated with RT, while patients with Stage II were treated with CCRT (concurrent chemotherapy: 5FU, cisplatin or TS-1). The median follow-up period was 81 months, ranging from 15 to 155 months. The 5-year overall survival rates, cause specific survival rates, locoregional control rates, and progression-free survival rates were 58, 75, 56, and 49 %, respectively. Of the 33 patients, 51 % experienced second primary malignancies. Esophageal carcinoma occurred in several cases, and was diagnosed either during screening after treatment for the second primary malignancy or simultaneously with the second primary malignancy. Advanced-stage second malignancies significantly influenced the survival of the patients and the control rate for HPSCC. Treatment emphasizing the quality of life after treatment is needed, if a poor prognosis is expected because of advanced-stage second primary malignancy.

[Concurrent chemoradiotherapy for resectable locoregionally advanced squamous cell carcinoma of the head and neck-analysis of factors associated with toxicity and efficacy].

We evaluated clinical factors associated with concurrent chemoradiotherapy (CRT) toxicity and efficacy in resectable locoregionally advanced squamous cell carcinoma of the head and neck. Subject were 115 subjects with stage III or IV carcinoma undergooing 58 to 70 Gy of irradiation (median total dose: 66 Gy) concurrently with 2 cycles of chemotherapy of 5FU at 1000 mg/m2, 120-hour continuous infusion and cisplatin at 60 mg/m2. Grade 3 to 4 mucositits differed significantly between 13% in N0 and 59% in N1 to 2. No significant difference in planned therapy completion was seen between 87% in N0 and 82% in N1 to 2. Three-year overall survival (OS) was 66% and progression-free survival (PFS) 55%, in median follow-up of 42 months (range: 5.8 to 91 months). OS differed significantly between 86% in stage III and 57% in IV, 78% in T0 to 2 and 62% in T3 to 4, 83% in N0 to 1 and 53% in N2, 77% in adjuvant chemotherapy (nedaplatin plus UFT) and 50% in no adjuvant chemotherapy, and 33% in the tongue and 77% in the oropharynx. PFS significantly differed between 72% in T0 to 2 and 49% in T3 to 4, 77% in CR and 53% in PR, and 22% in the tongue and 58% in the hypopharynx, 66% in the oropharynx, and 53% in the larynx. Multivariable analysis showed strongly independent risk factors associated with OS and PFS to be advanced T and N stage, no adjuvant chemotherapy, and the tongue as the site. CRT was effective in treating resectable locoregionally advanced squamous cell carcinoma of the head and neck. It is possible that adjuvant chemotherapy will improve CRT OS and PFS. Other additional treatment will be needed, however, to improve OS and PFS in cases having a dismal diagnosis such as tongue cancer.

[Parotid gland cancer treatment with facial nerve preservation].

Based on clinical features in 34 cases of parotid gland cancer treated between January 1997 and December 2007, tumor, node, and metastasis classification found 5 subjects to be T1, 12 to be T2, 7 to be T3, and 10 to be T4a. Of these, 25 were staged for N0, 3 for N1, and 6 for N2. Histopathologically, 10 different tumor types were observed, with carci-noma ex pleomorphic adenoma the most common. Preoperative fine-needle aspiration cytology (FNAC) of parotid gland tumor was done on 126 and cytological findings compared to histopathologic diagnoses of surgically resected specimens. Sensitivity for malignancy was 76.0%, specificity 95.4%, and overall accuracy 91.1%. Six malignant tumors were diagnosed as benign and 4 benign as malignant by FNAC, indicating that FNAC results alone may not be sufficient for diagnosing malignancy definitively. Among subjects, 25 underwent surgical resection, with the facial nerve preserved in 15 of 29. Postoperative radiotherapy was indicated if lymph node metastasis, intermediate or high-grade malignancy, or positive margins were seen. Of 15 subjects undergoing postoperative radiotherapy, 3 experienced recurrence. For unresectable tumors, concurrent chemoradiotherapy was used for 3 subjects and 2 underwent radiotherapy alone, with all 5 current survivors. The 5-year overall survival (OS) was 87.4% and progression-free survival (PFS) 71.4%. In terms of 5-year PFS, significant differences were seen between stage I/II (91.7%) and stage III/IW (51.6%) (P=0.032), and between N0 (86.2%) and N+ (38.1%) (P=0.002).

Diagnosis of lymph node metastases of head and neck cancer and evaluation of effects of chemoradiotherapy using ultrasonography.

BACKGROUND: Ultrasonographic diagnostic criteria were established to detect cervical metastatic lymph nodes including those up to 10 mm in thickness. Ultrasonography can diagnose not only cervical metastatic lymph nodes but can also be used to evaluate treatment-induced changes in lymph node metastases, one by one or degeneration of metastatic lesion in remaining lymph nodes after chemoradiotherapy. METHODS: A high-frequency probe of 7.5 MHz or higher was used in the ultrasonographic diagnosis of cervical lymph node metastases, using B-mode, Doppler blood flow imaging, and tissue elasticity imaging. Cervical lymph node metastases of head and neck squamous cell carcinoma were diagnosed according to ultrasonographic lymph node metastasis criteria. These criteria consist of the thickness of a lymph node (more than 6 mm or not), and existence of intra-lymph nodal occupying lesions suspected as a metastatic focus or not. Furthermore, metastatic lymph nodes remaining without regression after chemoradiotherapy were also evaluated according to therapeutic effect, using ultrasonography, and we examined the efficacy of ultrasonography to predict clinical outcomes. RESULTS: These diagnostic criteria enabled the accurate diagnosis of metastatic lymph nodes that were up to 10-mm-thick; such nodes are difficult to diagnose by computed tomography (CT) or magnetic resonance imaging (MRI). Moreover, examination of therapeutic effects such as decreased blood flow into a metastatic focus, and softening of a lymph node, by evaluating B-mode dynamic images or employing tissue elasticity imaging, was also useful to determine the effectiveness of chemoradiotherapy and a favorable outcome. CONCLUSION: Ultrasonographic diagnostic criteria for cervical metastatic lymph nodes enabled accurate diagnosis. Ultrasonographic evaluation of therapeutic effects on cervical lymph node metastases revealed not only the control of metastasis in the cervical region but also the clinical course and control of the primary site.

[Concurrent chemoradiotherapy for squamous cell carcinoma of the oropharynx].

Subjects were 34 patients, 32 men and 2 women, with squamous cell carcinoma of the oropharynx, with a median age of 63 years (range, 47 to 72 year). Subsites were the lateral wall in 18, anterior wall in 10, posterior wall in 5 and superior wall in 1. Nine had stage III disease and 25 had stage IV disease. Nineteen cases were resectable and 15 cases were unresectable. The patients were treated with concurrent chemoradiotherapy. The treatment regimen consisted of 5-fluorouracil (5-FU) and cisplatin (CDDP). 5-FU was given at 1000mg/m2 per day as a continuous infusion over 4 days, and CDDP was given at 60mg/m2 on day 4 after the start of 5-FU administration. Two courses of chemotherapy were administered, on day 1 and day 35. Radiation was given at a single daily fraction of 2Gy and 5 fractions per week were administered up to a total dose of 58 to 70Gy. Radiation break was scheduled from day 26 to 35. The median total delivered dose of radiation was 66Gy. Toxicities included mucositis (grade 3, 23.6%, grade 4, 38.2%), vomiting (grade 3, 14.7%) and leukopenia (grade 3, 20.6%). Twenty-eight patients (82.3%) received the treatment as scheduled. Seven (22.6%) showed a complete response and 22 (70.9%) showed partial response. The mean overall survival rate was 23 months (4.5-73.5) and progression-free survival (PFS) rate was 20 months (4.5-71.3). The two-year preservation rate of the oropharynx without recurrence was 45.0%. The two-year overall survival (OS) rate was 57.1% and PFS rate was 55.1%. Significant differences among groups were observed in the two-year overall survival and progression-free survival rate, as follows: 84.6% and 88.8%, respectively, in the resectable cases, and 33.3% and 26.7%, respectively, in the unresectable cases, and 60.6% and 63.2%, respectively, in the T2 + 3 cases and 40.0% and 0%, respectively in the T4 cases. Failure patterns were noted in 15 cases with locoregional recurrence in 14 and other disease in one. Based on the results it is concluded that concurrent chemoradiotherapy is effective for preserving the oropharynx in a high percentage of patients and for improving the two-year OS and PFS rates without compromising the QOL.

[Clinical application of real-time tissue elastography to head and neck cancer--evaluation of cervical lymph node metastasis with real-time tissue elastography].

Real-time tissue elastography (elastography) is a new ultrasonography procedure that display tissue elasticity. We evaluated the usefulness of elastography in the diagnosis of cervical lymph node metastasis and its treatment results in patients with head and neck cancer. Metastatic lymph nodes tended to produce little distortion when displayed as hard tumors, and produced distortion, displayed as soft tumors, after radiation therapy and/or chemotherapy. Elastography thus is useful as a potential new diagnostic procedure in the diagnosis of neck lymph node metastasis in head and neck cancer.

[Adjuvant chemotherapy (nedaplatin/UFT) after concurrent chemoradiotherapy for locally advanced head and neck squamous cell carcinoma].

To evaluate the efficacy of adjuvant chemotherapy after concurrent chemoradiotherapy, 41 previously untreated patients with locally advanced and resectable head and neck squamous cancer were enrolled in a study to compare adjuvant chemotherapy (Nedaplatin/UFT) after concurrent chemoradiotherapy (CDDP/5-FU) and concurrent chemoradiation alone. Nine of the patients had stage III tumors and 32 had stage IV tumors. The primary tumor site was the hypopharynx in 14 patients, the larynx in 12 patients, the oral cavity in 9 patients, and the oropharynx in 6 patients. Treatment consisted of 6 courses of Nedaplatin (80 mg/m2) repeated at 4-week intervals and one year of the oral administration of UFTE (400 mg/day) after concurrent chemoradiotherapy at an outpatient clinic. Toxicities included leukopenia (grade 3, 15.4%) and thrombocytopenia (grade 3, 7.7%). One death from a gastric ulcer occurred. The median overall survival time was 30.1 months (5.5-50.1 months) for the adjuvant chemotherapy group and 21.7 months (4.0-48.8 months) for the control group. The progression-free survival period was 22.8 months (5.6-33.9 months) for the adjuvant chemotherapy group and 26.5 months (5.6-33.9 months) for the control group. The two-year overall survival rate was 73.3% for the adjuvant chemotherapy group and 55.7% for the control group. A significant difference was observed in the two-year progression-free survival rates: 66.9% for the adjuvant chemotherapy group and 27.8% for the control group (p = 0.03290). Among the patients with a partial response to concurrent chemoradiotherapy, in particular, a significant difference in the two-year progression-free survival rates was seen : 59.3% for the adjuvant chemotherapy group and 15.3% for the control group (p = 0.01102). The rate of loco-regional failure was 29.6% for the adjuvant chemotherapy group and 64.3% for the control group (p = 0.0716). Distant metastasis was not detected in either group. The rate of organ preservation was 66.7% for the adjuvant chemotherapy group and 35.7% for the control group (p = 0.1183). This adjuvant chemotherapy regimen might improve the loco-regional control rates after concurrent chemoradiotherapy.

Evaluation of soluble adhesion molecules CD44 (CD44st, CD44v5, CD44v6), ICAM-1, and VCAM-1 as tumor markers in head and neck cancer.

PURPOSE: Standard CD44 (CD44st), CD44 variant 5 (CD44v5), and CD44 variant 6 (CD44v6), intercellular adhesion molecule 1(ICAM-1), and vascular cell adhesion molecule 1(VCAM-1) are expressed in human malignant cells and tissues. Their mechanism remains unclear but has been reported to be associated with the progression and metastasis of malignancies. MATERIALS AND METHODS: In this study, we investigated any correlations between the soluble adhesion molecule CD44 (st, v5, and v6), ICAM-1, and VCAM-1 and the clinicopathologic variables (eg, age, sex, histological grading, tumor size, lymph node status, distant metastasis, and TNM staging) and evaluated the difference between the pretreatment level in the patients with head and neck cancer and that in the control group. Furthermore, we examined the difference between the pretreatment serum levels and the after-treatment serum levels in the group with head and neck cancer. The pretreatment and after-treatment serum levels of soluble CD44st, CD44v5, CD44v6, ICAM-1, and VCAM-1 were measured in 81 patients with head and neck cancer and in 20 healthy volunteers as controls. RESULTS: There were no significant differences between the serum levels of sCD44st, sCD44v5, sCD44v6, sICAM-1, and sVCAM-1 and the clinicopathologic variables in cancer patients. However, the higher serum level of sCD44v6 was significantly associated with distant metastasis (P = .02). Especially, we found that the pretreatment serum levels of sCD44st, sCD44v5, and sCD44v6 were markedly associated with TNM staging (CD44st P = .0017, CD44v5 P = .0005, CD44v6 P = .0046). Furthermore, the median serum levels of sCD44st, sCD44v5, sCD44v6, sICAM-1, and sVCAM-1 before treatment of head and neck cancer were significantly higher than those of the control group (CD44st P = .0067, CD44v5 P = .0048, CD44v6 P = .0007, ICAM-1 P = .0089, VCAM-1 P = .0178). The median serum level of sCD44st after treatment in the group of patients was significantly lower than that of pretreatment (CD44st P = .0001). And, both the median serum levels of sCD44v5 and sCD44v6 after treatment were also lower than those of pretreatment (CD44v5 P = .0004, CD44v6 P = .0025). CONCLUSIONS: The possible roles of soluble adhesion molecules in the prognosis of head and neck carcinoma deserve further elucidation and evaluation with long-term patient follow-up.