Selective neck irradiation for supraglottic cancer: focus on Sublevel IIb omission.

OBJECTIVE: To estimate selective neck irradiation omitting surgical Sublevel IIb. METHODS: Bilateral necks of 47 patients (94 necks) were subjected to definitive radiotherapy for supraglottic cancer. Sixty-nine and 25 necks were clinically node negative (cN-) and clinically node positive (cN+), respectively. We subdivided Sublevel IIb by the international consensus guideline for radiotherapy into Sublevel IIb/a, directly posterior to the internal jugular vein, and Sublevel IIb/b, which was behind Sublevel IIb/a and coincided with surgical Sublevel IIb. Bilateral (Sub)levels IIa, III, IV and IIb/a were routinely irradiated, whereas Sublevel IIb/b was omitted from the elective clinical target volume in 73/94 treated necks (78%). RESULTS: Two patients presented with ipsilateral Sublevel IIb/a metastases. No Sublevel IIb/b metastasis was observed. Five patients experienced cervical lymph node recurrence; Sublevel IIb/a recurrence developed in two patients, whereas no Sublevel IIb/b recurrence occurred even in the cN- necks of cN+ patients or cN0 patients. The 5-year regional control rates were 91.5% for Sublevel IIb/b-omitted patients and 77.8% for Sublevel IIb/b treated patients. CONCLUSIONS: Selective neck irradiation omitting Sublevel IIb/b did not compromise regional control and could be indicated for cN- neck of supraglottic cancer.

Endoscopic submucosal dissection as minimally invasive treatment for superficial pharyngeal cancer: a phase II study (with video).

BACKGROUND AND AIMS: Although endoscopic submucosal dissection (ESD) has been applied for superficial pharyngeal cancer, no prospective trials have been reported. To investigate the efficacy and safety of ESD for superficial pharyngeal cancer, we conducted a prospective phase II trial. METHODS: Fifty-four patients with 73 lesions were enrolled from September 2010 to August 2014, and ESD was performed. The primary endpoint was the complete resection rate. Secondary endpoints were safety, recurrence-free survival, overall survival, and incidence of metachronous pharyngeal cancer. RESULTS: Fifty-four patients had stage 0-III cancer: stage 0, n = 22; stage I, n = 14; stage II, n = 17; and stage III, n = 1. The en bloc resection rate was 100%, and the complete resection rate was 79.5% (58/73 lesions; 95% confidence interval, 68%-88%). No serious adverse events related to ESD were encountered. Four patients required nasogastric intubation and feeding. No patients required percutaneous endoscopic gastrostomy and tracheotomy. Swallowing, speech, and airway functions were preserved in all patients. One of the 54 patients died of an unrelated illness. Median follow-up was 27 months (range 6-55 months). Local cervical lymph node metastasis was observed in 1 patient, and the case was salvaged successfully with lymph node dissection. The 3-year overall and recurrence-free survival rates were 97.7% and 98.1%, respectively. Cumulative development of multiple cancers of the pharynx at 3 years was 18.4%. CONCLUSIONS: ESD appears to be a safe and effective minimally invasive treatment in patients with superficial pharyngeal cancer. ( CLINICAL TRIAL REGISTRATION NUMBER: UMIN000003623.).

Lymph node metastasis in t4 maxillary sinus squamous cell carcinoma: incidence and treatment outcome.

BACKGROUND: The purpose of this study was to evaluate the incidence of lymph node metastasis among patients with T4 maxillary sinus squamous cell carcinoma (MS-SCC) as well as the delayed metastasis rate and the treatment outcome for untreated N0 neck in patients with T4 MS-SCC. METHODS: Consecutive series of all patients (n = 128) with previously untreated T4 maxillary sinus SCC between 2006 and 2007 were obtained from 28 institutions belonging to or cooperating in the Head and Neck Cancer Study Group of the Japan Clinical Oncology Group. RESULTS: Of the 128 patients, 28 (21.9 %) had lymph node metastasis, and six patients (4.7 %) had distant metastasis at diagnosis. Among the 111 patients who were treated with curative intent, 98 had clinically N0 neck disease and did not receive prophylactic neck irradiation. A total of 11 patients (11.2 %) subsequently developed evidence of lymph node metastasis, of whom eight were among the 83 patients with an N0 neck and had not received elective neck treatment. There were 15 patients who received an elective neck dissection as part of the initial treatment, of whom three had pathologically positive for lymph node metastases. Of 11 patients, six patients with nonlateral retropharyngeal lymph node metastasis without primary or distant disease were successfully salvaged. CONCLUSIONS: This study identified the incidence of lymph node metastasis among patients with T4 MS-SCC as well as the delayed metastasis rate and the treatment outcome for untreated N0 neck in patients with T4 MS-SCC. These results will be of assistance in selecting treatment strategy for T4 MS-SCC in the future.

Boerhaave's syndrome in a tracheoesophageal speaker: report of a case.

Boerhaave's syndrome is still associated with a high mortality rate and remains a therapeutic challenge. Pharyngo-laryngo-esophagectomy is performed as the standard treatment for advanced hypopharyngeal cancer and tracheoesophageal speech is an option for esophageal speech rehabilitation. We report what, to our knowledge, is the first case of Boerhaave's syndrome developing in a tracheoesophageal speaker.

[Outcome of tongue cancer treated with surgery and postoperative radiotherapy].

A retrospective analysis of 263 patients with previously untreated squamous cell carcinoma of the tongue between 2000 and 2010 was performed. Those patients, who received preoperative chemotherapy, had a history of head and neck cancer or had previously received radiotherapy for the other disease, were excluded. All patients underwent a surgical procedure as a part of the initial treatment. Patients with close or microscopically involved margins of resection, INF (Infiltrative growth pattern) gamma or at least two involved nodes were classified as high risk patients. Postoperative radiotherapy (PORT) was undertaken for the high risk patients. After a median follow-up of 72 months, the 5-year overall survival and 5-year cause-specific survival were as follows: 79.1%, 85.0% in all stages, 82.7%, 91.2% in Stage I (n = 76), 86.7%, 89.0% in Stage II (n = 98), 71.5%, 78.6% in Stage III (n = 57), and 61.5%, 69.1% in Stage IV (n = 32). Patients without high risk features had significantly higher overall survival rate than those in the case of high risk patients, despite receiving no PORT. For high risk patients, PORT significantly improved the locoreginal control rate, but the overall survival rate did not improve.

Matched-pair analysis in patients with advanced oropharyngeal cancer: surgery versus concurrent chemoradiotherapy.

OBJECTIVE: The current study aimed to compare the therapeutic outcomes of surgery with those of chemoradiation for patients with advanced oropharyngeal cancer (OPC). METHODS: The data for 523 patients with previously untreated OPC were obtained from 12 institutions belonging to the Head and Neck Cancer Study Group in the Japan Clinical Oncology Group from April 2005 to March 2007. In this study, we matched a group of patients who underwent surgery with a second group treated with chemoradiation according to age, gender, subsite, and T and N classification, and analyzed the overall survival, progression-free survival, local control and swallowing function. RESULTS: The final matched-pair analysis included 186 patients. The 5-year overall survival, progression-free survival and local control rates were 69.8 and 71.4% (p = 0.762), 51.0 and 54.4% (p = 0.531), and 75.2 and 80.3% (p = 0.399), respectively, in patients treated with surgery and those treated with chemoradiation. Swallowing function in patients treated with chemoradiation was significantly better than that in patients treated with surgery (p = 0.015). CONCLUSION: Although this study was not randomized, this matched-pair analysis of patients treated with surgery or chemoradiation showed that chemoradiation is as effective as surgery in the treatment of OPC.

Salvage surgery for recurrent oropharyngeal cancer after chemoradiotherapy.

BACKGROUND: The current study aimed to assess the role of salvage surgery for failure cases of oropharyngeal cancer (OPC) undergoing initial chemoradiotherapy (CRT). METHODS: The data for 523 patients with previously untreated OPC were gathered from 12 institutions belonging to the Head and Neck Cancer Study Group in Japan Clinical Oncology Group (JCOG). RESULTS: Of the 170 patients who received CRT, 35 patients (21%) had local recurrence or residual disease. Only 11 patients underwent further salvage surgery, and 24 patients received nonsurgical treatment. There were statistically significant differences between the two groups in terms of patient age and the presence of a simultaneous regional recurrence. The 5-year overall survival rates for the patients who underwent salvage surgery were 49.1%, whereas those for the patients who received nonsurgical treatment were 16.3%. CONCLUSION: The initial treatment method for OPC should be decided carefully and the limitations of salvage surgery should be fully considered.

Defining PET standardized uptake value threshold for tumor delineation with metastatic lymph nodes in head and neck cancer.

OBJECTIVE: Hot spots of F-18 fluorodeoxyglucose positron emission tomograms are variable in size according to window settings of standardized uptake values. The purpose of this study was to determine the standardized uptake value threshold that represents the target volume. METHODS: Sixty-three patients who underwent fluorodeoxyglucose positron emission tomographic computed tomography and were diagnosed as having head and neck cancer with cervical lymphadenopathy were studied. The horizontal and vertical diameters of metastatic lymph nodes (LN-CT) were measured at the center of computed tomographic images. Of the corresponding nodes, the maximal standardized uptake value (SUVmax) and standardized uptake value profiles along the central horizontal and vertical axes were calculated on positron emission tomographic images (LN-PET). On the standardized uptake value profiles, the standardized uptake value levels (SUVeq) where the size of LN-PET was equivalent to the diameters of LN-CT were obtained. The regression formula between SUVeq and SUVmax was obtained. The regression formula of SUVeq was validated in subsequent 30 positron emission tomographic computed tomography studies. RESULTS: The mean horizontal and vertical diameters of LN-CT were 14.9 and 16.4 mm, respectively. SUVmax ranged from 1.88 to 9.07, and SUVeq was between 1.16 and 6.42. The regression formula between SUVeq and SUVmax was as follows: SUVeq = 1.21 + 0.34 × SUVmax (coefficient of correlation: R = 0.69). The validation study resulted in a good correlation between the volume of lymph nodes on computed tomography and positron emission tomographic computed tomography (R(2) = 0.93). CONCLUSIONS: The formula with a relatively high coefficient of correlation is considered to indicate that SUVeq is not constant, but is a complex of an absolute standardized uptake value and is proportional to SUVmax.

A case of myxofibrosarcoma of the maxilla with difficulty in preoperative diagnosis.

Myxofibrosarcoma (MFS) is a very rare fibroblast-derived sarcoma that occurs in the head and neck region. Here, we report the case of a 52-year-old man in whom MFS generated from the maxilla and whose beginning of treatment was considerably delayed because he was initially diagnosed as having a benign inflammatory lesion. Because a definite diagnosis was not obtained via 2 independent biopsies, total maxillectomy was used for both diagnosis and treatment. Histopathological and immunohistochemical analyses suggested that the tumor was a low-grade MFS. Because soft tissue tumors in the head and neck region are rare and a definite diagnosis is relatively difficult, surgical excision is indispensable if malignancy of the tumor is suspected.

[Nutritional surveillance in head and neck cancer patients during radiotherapy--the difference between concurrent chemoradiotherapy using high-dose cisplatin and radiotherapy alone].

Concurrent chemoradiotherapy (CCRT) has been widely used in organ preservation for advanced head and neck squamous cell carcinoma. Malnutrition, one of the most detrimental side effects concerned with CCRT, occurs frequently in patients with CCRT, but few studies have reported on the nutritional status in detail during CCRT. The aim of this study was to evaluate the changes in the nutritional status during CCRT compared with radiotherapy alone (RT). We introduce hypopharyngeal cancer patients as the subjects that include 26 cases who underwent CCRT with high dose cisplatin (80 mg/m2 x 3: goal 240 mg/m2 in total) and also 26 cases who underwent RT during the same period. For evaluation, we examined the rate of body weight change, serum albumin, total lymphocyte counts and hemoglobin. In this context, the rate of body weight change is the most reliable indicator, and the rate of change at the end of treatment as compared to before the start of treatment was 3.8% in patients treated with RT and 8.1% in patients treated with CCRT. This result suggests that improvement in nutritional status is necessary when considering patients undergoing CCRT. However, regarding completion of treatment, when radiotherapy was not interrupted due to adverse events the median total dose of cisplatin of 240 mg/m2 seemed satisfactory. In addition, regarding the route for energy intake, tube feeding was required only in 2 patients (7.7%) in the RT group and 4 patients (15.4%) in the CCRT group, and no significant difference was found between them. Therefore, percutaneous endoscopic gastrostomy (PEG) for CCRT in advance would be unnecessary at least for hypopharyngeal cancer patients.

Ascending pharyngeal-vertebral anastomosis demonstrated by computed tomography angiography of the ascending pharyngeal artery: a case report.

Ascending pharyngeal-vertebral anastomosis has been identified by angiography of the carotid artery in several cases. We present a case of ascending pharyngeal-vertebral anastomosis that was found incidentally in computed tomography angiography of the ascending pharyngeal artery. Images revealed that the anastomosis formed through the hypoglossal branch of the neuromeningeal trunk. The anastomosis seemed to be associated with hypoplasia of the right vertebral artery. Interventional radiologists should be aware of this dangerous anastomotic route of the APA to the VA. Discovery of hypoplasia of the major intracranial arteries before intra-arterial chemotherapy or embolization in head and neck area may avoid subsequent complications.

Significance of endoscopic screening and endoscopic resection for esophageal cancer in patients with hypopharyngeal cancer.

OBJECTIVE: The efficacy of endoscopic screening for esophageal cancer in patients with hypopharyngeal cancer remains controversial and its impact on prognosis has not been adequately discussed. We studied the use of endoscopic screening to detect esophageal cancer in hypopharyngeal cancer patients by analyzing the incidence, stage and prognosis. METHODS: We included 64 patients with hypopharyngeal cancer who received radical radiotherapy at our institute. Chromoendoscopic esophageal examinations with Lugol dye solution were routinely performed at and after treatment for hypopharyngeal cancer. RESULTS: Twenty-eight esophageal cancers were detected in 28 (41%) patients (18 synchronous and 10 metachronous cancers). Of the 28 cancers, 23 were stage 0 or I cancer and 15 of these were treated with endoscopic resection. Local control was achieved in all of these 23 stage 0 or I cancers. The 5-year overall survival rates with esophageal cancer were 83% in stage 0, 47% in stage I and 0% in stage IIA-IVB. CONCLUSIONS: This study showed a strikingly high incidence of esophageal cancer in hypopharyngeal cancer patients. We suppose that the combination of early detection by chromoendoscopic examination and endoscopic resection for associated esophageal cancer in hypopharyngeal cancer patients improve prognosis and maintain quality of life.

Clinicopathological significance of cyclooxygenase-2 expression in hypopharyngeal squamous cell carcinoma.

The purpose of this study was to determine the expression of cyclooxygenase-2 (COX-2) in normal epithelium, dysplasia and squamous cell carcinoma of the hypopharynx and to investigate associations with clinicopathological factors and survival. Seventy-five patients with hypopharyngeal squamous cell carcinomas (HPSCC) who underwent surgical treatment at the Department of Otolaryngology, Osaka Medical Center for Cancer and Cardiovascular Diseases, were investigated. COX-2 expression was determined by immunohistochemistry and 97.3% (73/75) of samples displayed immunostaining in tumor cells. COX-2 staining was localized mainly in the cytoplasm (73/75) and was rare in stromal cells (2/75). Over half of the areas of dysplastic cells adjacent to carcinomas also showed COX-2 staining (41/70, 58.6%). There were no significant correlations between the COX-2 expression and tumor size, location and tumor growth type, T- and N-stage, tumor recurrence, lymph node metastasis and survival in this study. COX-2 expression thus does not appear to have a prognostic significance for hypopharyngeal SCC although there was a tendency for higher values in T3/T4 than T1/T2 cases. Furthermore, COX-2 was found to be more strongly expressed in poorly-differentiated than in moderately/well-differentiated carcinomas. In this study group, COX-2 was up-regulated not only in SCCs but also in the dysplastic lesions of the hypopharynx, suggesting that COX-2 inhibition may be a useful chemopreventive strategy.

Adjuvant chemotherapy with S-1 after curative chemoradiotherapy in patients with locoregionally advanced squamous cell carcinoma of the head and neck: Reanalysis of the ACTS-HNC study.

BACKGROUND: Chemoradiotherapy (CRT) has improved organ preservation or overall survival (OS) of locoregionally advanced head and neck squamous cell cancer (LAHNSCC), but in clinical trials of conventional CRT, increasing CRT intensity has not been shown to improve OS. In the Adjuvant ChemoTherapy with S-1 after curative treatment in patients with Head and Neck Cancer (ACTS-HNC) phase III study, OS of curative locoregional treatments improved more with adjuvant chemotherapy with S-1 (tegafur gimeracil oteracil potassium) than with tegafur/uracil (UFT). ACTS HNC study showed the significant efficacy of S-1 after curative radiotherapy in sub-analysis. We explored the efficacy of S-1 after curative CRT in a subset of patients from the ACTS-HNC study. METHODS: Patients with stage III, IVA, or IVB LAHNSCC were enrolled in this study to evaluate the efficacy of S-1 compared with UFT as adjuvant chemotherapy after curative CRT in the ACTS-HNC study. Patients received S-1 at 80-120 mg/day in two divided doses for 2 weeks, followed by a 1-week rest, or UFT 300 or 400 mg/day in two or three divided doses daily, for 1 year. The endpoints were OS, disease-free survival, locoregional relapse-free survival, distant metastasis-free survival (DMFS), and post-locoregional relapse survival. RESULTS: One hundred eighty patients (S-1, n = 87; UFT, n = 93) were included in this study. Clinical characteristics of the S-1 and UFT arms were similar. S-1 after CRT significantly improved OS (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.22-0.93) and DMFS (HR, 0.50; 95% CI, 0.26-0.97) compared with UFT. CONCLUSION: As adjuvant chemotherapy, S-1 demonstrated better efficacy for OS and DMFS than UFT in patients with LAHNSCC after curative CRT and may be considered a treatment option following curative CRT. For this study was not preplanned in the ACTS-HNC study, the results is hypothesis generating but not definitive.

Multi-institutional retrospective study for the evaluation of ocular function-preservation rates in maxillary sinus squamous cell carcinomas with orbital invasion.

BACKGROUND: The purpose of this retrospective analysis was to evaluate ocular function and survival rates among treatment modalities in patients with maxillary sinus cancer with orbital invasion. METHODS: Eighty-seven patients were classified according to the main treatment modality. Ocular function preservation rates and survival rates were evaluated for each therapeutic modality. RESULTS: The 5-year overall survival rate for the en bloc resection, conservative surgery, superselective intra-arterial chemotherapy, and radiotherapy (RADPLAT), intravenous chemoradiotherapy (IV-CRT) was 70%, 35%, 49%, and 31%, respectively. The ocular function preservation rate for each group was 15%, 27%, 30%, and 17%, respectively. In the en bloc resection group, there was no significant difference in the 5-year overall survival rate between patients with orbital exenteration and those without orbital exenteration (72% vs 71%; p = .9321). CONCLUSION: The en bloc resection group showed a favorable survival rate but a low preservation rate. Preservation of orbital contents did not reduce the survival rate.

Randomized phase III trial of adjuvant chemotherapy with S-1 after curative treatment in patients with squamous-cell carcinoma of the head and neck (ACTS-HNC).

BACKGROUND: We conducted a phase III study to evaluate S-1 as compared with UFT as control in patients after curative therapy for stage III, IVA, or IVB squamous-cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Patients were randomly assigned to the UFT group (300 or 400 mg day-1 for 1 year) or the S-1 group (80, 100, or 120 mg day-1 for 1 year). The primary end point was disease-free survival (DFS). Secondary end points were relapse-free survival, overall survival (OS), and safety. RESULTS: A total of 526 patients were enrolled, and 505 were eligible for analysis. The 3-year DFS rate was 60.0% in the UFT group and 64.1% in the S-1 group (HR, 0.87; 95%CI, 0.66-1.16; p = 0.34). The 3-year OS rate was 75.8% and 82.9%, respectively (HR, 0.64; 95% CI, 0.44-0.94; p = 0.022). Among grade 3 or higher adverse events, the incidences of leukopenia (5.2%), neutropenia (3.6%), thrombocytopenia (2.0%), and mucositis/stomatitis (2.4%) were significantly higher in the S-1 group. CONCLUSIONS: Although DFS did not differ significantly between the groups, OS was significantly better in the S-1 group than in the UFT group. S-1 is considered a treatment option after curative therapy for stage III, IVA, IVB SCCHN. TRIAL REGISTRATION: ClinicalTrials.gov NCT00336947 http://clinicaltrials.gov/show/NCT00336947.