Radiotherapy alone as a possible de-intensified treatment for human papillomavirus-related locally advanced oropharyngeal squamous cell carcinoma.

BACKGROUND: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is defined by p16 positivity and/or HPV DNA positivity. Because survival of patients with HPV-related OPSCC after chemoradiotherapy is favorable, a de-intensified treatment is expected to lead to less morbidity while maintaining low mortality. The association of tumor p16 and HPV DNA status with survival after radiotherapy alone remains unknown. METHODS: We retrospectively examined survival of 107 patients with locally advanced OPSCC after radiotherapy alone (n = 43) or chemoradiotherapy (n = 64) with respect to tumor p16 and HPV DNA status, using Cox's proportional hazard model. RESULTS: Survival after radiotherapy alone was significantly worse in p16-positive/HPV DNA-negative locally advanced OPSCC than in p16-positive/HPV DNA-positive locally advanced OPSCC. In bivariable analyses that included T category, N category, TNM stage, and smoking history, the survival disadvantage of p16-positive/HPV DNA-negative locally advanced OPSCC remained significant. There was no significant difference in survival after chemoradiotherapy between p16-positive/HPV DNA-positive locally advanced OPSCC and p16-positive/HPV DNA-negative locally advanced OPSCC. Survival in p16-positive/HPV DNA-positive locally advanced OPSCC after radiotherapy alone was similar to that after chemoradiotherapy, which stayed unchanged in bivariable analyses after adjustment of every other covariable. Survival of p16-negative/HPV DNA-negative locally advanced OPSCC was poor irrespective of treatment modality. CONCLUSIONS: Survival in p16-positive locally advanced OPSCC differs depending on HPV DNA status. Radiotherapy alone can serve as a de-intensified treatment for p16-positive/HPV DNA-positive locally advanced OPSCC, but not for p16-positive/HPV DNA-negative locally advanced OPSCC.

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.

Chemoradiotherapy with weekly low-dose docetaxel and cisplatin concurrent with radiation for patients with locally advanced nasopharyngeal carcinoma, followed by adjuvant chemotherapy for selected patients.

OBJECTIVE: We investigated the efficacy and safety of concurrent chemoradiotherapy using weekly low-dose docetaxel and cisplatin in patients with locally advanced nasopharyngeal carcinoma. METHODS: This was a retrospective analysis of 31 patients who were treated with this regimen from 2001 to 2014. Concurrent chemoradiotherapy consisted of radiotherapy with a total dose of 59.4-70.2 Gy plus weekly administration of docetaxel (5-10 mg/m2) and cisplatin (20 mg/m2), up to six cycles. At least two cycles of platinum-based adjuvant chemotherapy were prescribed for Stage IV and Stage III patients with partial response or stable disease after concurrent chemoradiotherapy. RESULTS: Of the 31 patients, 28 (90%) completed concurrent chemoradiotherapy as planned. The overall complete response and partial response rates were 42% and 52%, respectively. Seventeen of the 21 patients who were prescribed adjuvant chemotherapy underwent it. After a median follow-up of 39.1 months for the 23 surviving patients, 9 (29%) developed locoregional recurrence or progression and 6 patients (19%) developed distant metastasis. The 3-year overall survival and progression-free survival rates were 76% and 56%, respectively. Univariate analyses revealed that clinical stage was a significant predictor of complete response, overall survival and progression-free survival. The most serious adverse events were mucositis during concurrent chemoradiotherapy and neutropenia during adjuvant chemotherapy. CONCLUSIONS: This concurrent chemoradiotherapy protocol showed practical efficacy with high feasibility and acceptable toxicity. To improve the progression-free survival of patients with Stage IV disease who are treated by this protocol, changes to their treatment strategy should be considered.

Phase II study of docetaxel, cisplatin, and concurrent radiation followed by platinum-based adjuvant chemotherapy for technically unresectable, locally advanced head and neck squamous cell carcinoma.

BACKGROUND: Phase I study of weekly administration of low-dose docetaxel/cisplatin concurrent with conventionally fractionated radiotherapy for locally advanced head and neck squamous cell carcinoma suggested the recommended dose of docetaxel at 10 mg/m2 and cisplatin at 20 mg/m2. Phase II study of the concurrent chemoradiotherapy for technically resectable disease showed satisfactory results. METHODS: This phase II study was designed to address efficacy and safety when patients with technically unresectable disease were treated with concurrent chemoradiotherapy, followed by two cycles of moderate-dose platinum-based adjuvant chemotherapy: docetaxel, cisplatin, and fluorouracil (modified TPF). Modified TPF was replaced with docetaxel/carboplatin when renal impairment became evident. Surgical salvage was considered when residual or recurrent locoregional disease was technically resectable and free of distant metastasis. RESULTS: Of 33 enrolled patients, 31 were analyzable: 24 (78 %) and 18 (58 %) patients completed chemoradiotherapy and adjuvant chemotherapy, respectively; 15 (48 %) patients completed study treatment per protocol, and overall complete response rate was 45 %. Seven patients underwent surgical salvage, which was successful in 4 patients. At a median follow-up of 60.8 months for surviving patients, median progression-free survival and median overall survival were 16.2 and 39.9 months, respectively. Grade 3 or 4 toxicity included mucositis (77 %) and dysphagia (45 %) during the chemoradiotherapy period and neutropenia (100 %) and febrile neutropenia (35 %) during the adjuvant period. No patient died of toxicity. CONCLUSION: The tested regimen seems effective, although there is room for improvement in adjuvant chemotherapy because of the high toxicity and low compliance of modified TPF.

Trends in the Detail of the Stage and Survival Rate in Hypopharyngeal Cancer over 20 Years.

Background: Hypopharyngeal cancer frequently presents at an advanced stage and has one of the worst prognosis among the head and neck cancers. Recently, superficial hypopharyngeal cancers with a good prognosis have been detected with a novel endoscopic technique, such as narrow band imaging. Objectives: To evaluate trends in the detail of the stage and survival rate in hypopharyngeal cancer over 20 years. Patients and methods: Between 1993 and 2012, 722 patients with hypopharyngeal cancer treated at the Osaka Medical Center for Cancer and Cardiovascular Disease were studied retrospectively. The 20-year period was subdivided into 5-year periods; Period A (1993-1997, n=101), Period B (1998-2002, n=123), Period C (2003-2007, n=196) and Period D (2008-2012, n=302). The patients at Stage I-II were divided into superficial cancer as Stage I-IIs and invasive cancer as Stage I-IIi. In every period, a transition of the staging and overall survival rate were compared. Results: The 5-year overall survival in Period A, B, C and D were 34%, 39%, 54% and 60%, respectively. The patients at Stage III-IV in Period A, B, C and D comprised 32%, 36%, 47% and 54%, respectively. Both survival rates improved significantly from Period B to C. The ratio of Stage 0 and Stage I-IIs increased significantly from Period C to D. Whereas the 5-year overall survival rates of Stage 0 and Stage I-IIs were similar (80% vs 88%), the 5-year overall survival of Stage I-IIi was significantly poor. Excluding Stage 0 and Stage I-IIs, the 5-year overall survival had little change from Period C to D. Conclusion: The reason for the improvement in hypopharyngeal cancer prognosis was the prognostic improvement of advanced cancer from Period B to C, and an increase in superficial cancer from Period C to D.

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.).

Treatment outcomes of external-beam radiotherapy for squamous cell carcinoma of the base of the tongue.

PURPOSE: To evaluate definitive external-beam radiotherapy (EBRT) for patients with base of the tongue (BOT) cancers. METHODS: We reviewed results for 26 patients with BOT cancers who were treated with EBRT. Clinical stages T1, T2, T3, and T4a were observed for 10, 7, 4, and 5 patients, respectively, and stages N0, N1, N2a, N2b, N2c, and N3 were observed for 4, 2, 5, 6, 8, and 1 patients, respectively. More than half of the patients (n = 19) were stage IVA. Standard total delivered doses were 70 Gy to primary tumors and cervical lymph node (CLN) metastases and 40-46 Gy to elective nodal regions. Eleven patients with advanced loco-regional disease received concurrent or neoadjuvant chemotherapy. Four T3 patients and one T2 patient received 2 or 3 cycles of concurrent intra-arterial cisplatin with EBRT (RADPLAT). RESULTS: Three-year overall survival was 69 % (95 % CI 47-83 %), with a median follow-up period of 33 months. Three-year local control was 100, 86, 100, and 20 % for T1, T2, T3, and T4 patients, respectively. Three-year regional control was 100 % for N0, N1, and N2a, 83 % for N2b, 75 % for N2c, and 0 % for N3 patients. Treatment failed for 7 patients. All 5 patients undergoing RADPLAT achieved complete responses and did not develop local recurrence. CONCLUSIONS: We achieved favorable outcomes for patients with T1-T3 BOT cancers by use of definitive EBRT with or without chemotherapy.

[Videofluoroscopic Examination of Swallowing Using the AsR Score for Postoperative Swallowing Function in Oral Cancer Patients].

To evaluate the postoperative swallowing function in head and neck cancer patients, videofluoroscopic examination of swallowing (VF) proved useful as a qualitative evaluation, but was complex as a quantitative evaluation. We made use of the AsR score which consisted of a 10-point scale as a quantitative evaluation of VF. To identify the usefulness of the AsR score, 146 patients who had undergone extensive resection and reconstruction with free flaps or pedicle grafts were reviewed. The AsR score of VF for the first time after surgery was defined as "first score", and at the last time in the hospital was defined as "last score". The correlations between the first score and continuity of direct therapy, and between the last score and way of nutrition at the time of discharge were examined. Using the ROC (receiver operator characteristic) analysis and the AUC (area under the curve) the cut-off values of the AsR score were estimated. One hundred and thirty one patients could continue direct therapy after the first time of VF. The first score detected continuity of direct therapy with high accuracy (AUC = 0.946), furthermore using a cut-off of 5, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were about 96.2%, 86.6%, 98.4%, and 72.2%, respectively. At the time of discharge, 138 patients had no limitation of oral intake and 8 patients had a limitation e.g. PEG (n = 7) and a total laryngectomy for preventing aspiration (n = 1). The last score detected oral intake ability with no limitation with high accuracy (AUC = 0.925). Using a cut-off of 6, the sensitivity, specificity, PPV and NPV were about 82.6%, 87.5%, 99.1% and 22.6%, respectively. The AsR score is useful as a quantitative evaluation of postoperative swallowing function in oral cancer patients.

Human papillomavirus and p53 mutations in head and neck squamous cell carcinoma among Japanese population.

We aimed to reveal the prevalence and pattern of human papillomavirus (HPV) infection and p53 mutations among Japanese head and neck squamous cell carcinoma (HNSCC) patients in relation to clinicopathological parameters. Human papillomavirus DNA and p53 mutations were examined in 493 HNSCCs and its subset of 283 HNSCCs. Oropharyngeal carcinoma was more frequently HPV-positive than non-oropharyngeal carcinoma (34.4% vs 3.6%, P < 0.001), and HPV16 accounted for 91.1% of HPV-positive tumors. In oropharyngeal carcinoma, which showed an increasing trend of HPV prevalence over time (P < 0.001), HPV infection was inversely correlated with tobacco smoking, alcohol drinking, p53 mutations, and a disruptive mutation (P = 0.003, <0.001, <0.001, and <0.001, respectively). The prevalence of p53 mutations differed significantly between virus-unrelated HNSCC and virus-related HNSCC consisting of nasopharyngeal and HPV-positive oropharyngeal carcinomas (48.3% vs 7.1%, P < 0.001). Although p53 mutations were associated with tobacco smoking and alcohol drinking, this association disappeared in virus-unrelated HNSCC. A disruptive mutation was never found in virus-related HNSCC, whereas it was independently associated with primary site, such as the oropharynx and hypopharynx (P = 0.01 and 0.03, respectively), in virus-unrelated HNSCC. Moreover, in virus-unrelated HNSCC, G:C to T:A transversions were more frequent in ever-smokers than in never-smokers (P = 0.04), whereas G:C to A:T transitions at CpG sites were less frequent in ever-smokers than in never-smokers (P = 0.04). In conclusion, HNSCC is etiologically classified into virus-related and virus-unrelated subgroups. In virus-related HNSCC, p53 mutations are uncommon with the absence of a disruptive mutation, whereas in virus-unrelated HNSCC, p53 mutations are common, and disruptive mutagenesis of p53 is related with oropharyngeal and hypopharyngeal carcinoma.

Immediate effectiveness of humming on the supraglottic compression in subjects with muscle tension dysphonia.

AIMS: To verify whether humming corrects supraglottic compression in muscle tension dysphonia (MTD) patients. METHODS: We enrolled 23 MTD participants (13 male, 10 female) showing supraglottic compression. Each individual was instructed to perform 3 types of phonation under transnasal laryngofiberscopy: natural phonation, humming phonation without pitch change and subsequent um-hum phonation, i.e. humming with pitch glide up as if agreeing with someone. The degree of supraglottic compression was estimated with 2 parameters. The false vocal fold and anterior-posterior indices (the FVF and AP indices) were calculated by normalizing the lateral width and AP length of the visible vocal cords at phonation normalized to the mean vocal cord length at inspiration, respectively. These indices were compared among the tasks. RESULTS: All the MTD participants but 5 females accomplished decreases in the vocal roughness scores upon the phonatory tasks. The whole MTD group showed significant increases in the FVF and AP indices even after humming without pitch change with a dominance of the AP index. The humming-responsive MTD subgroup showed greater increases in both indices than the humming-resistant subgroup. CONCLUSION: These data demonstrate that humming corrects both the lateral and AP components of supraglottic compression in most MTD patients.

[A case of laryngeal necrosis following concurrent chemoradiotherapy for advanced hypopharyngeal cancer after insertion of a nasogastric tube].

A 62-year-old male with cT4bN2cM0 hypopharyngeal carcinoma with ipsilateral vocal cord fixation was initially treated with concurrent chemoradiotherapy. Since the patient complained of dysphagia caused by mucositis, a nasogastric tube was placed on the day of irradiation with a dose of 20 Gy. Bilateral vocal cord fixation and laryngeal necrosis became evident 3 weeks after the concurrent chemoradiotherapy. He underwent a total pharyngolaryngectomy (neck dissection, and reconstruction with a free jejunal graft) followed by adjuvant chemotherapy. It is highly suspected that the nasogastric tube compressed the mucosa of the post cricoid region, resulting in laryngeal necrosis.

[Head and neck soft tissue sarcoma].

Soft tissue sarcoma arising as a head and neck lesion is very rare in adults. Therefore, no standardized treatment exists for this entity of disease. We retrospectively analyzed 11 cases of head and neck soft tissue sarcomas treated at Osaka University Hospital from 1991 to 2011. They were pathologically classified as follows: 5 cases with rhabdomyosarcoma, 2 cases with liposarcoma, 2 cases with undifferentiated sarcoma and one each of epithelioid hemangioendothelioma and malignant fibrous histocytoma. Rhabdomyosarcomas were treated with multimodality therapy. Other sarcomas were treated mainly with surgery. The prognosis of patients with sarcoma depended on the histology, histological grade, tumor size and tumor stage. Patients with larger tumors, high grade tumors and advanced stage tumors had a poor prognosis, while those with rhabdomyosaracoma had a better prognosis. Further investigation is required to establish the new treatment protocol for adult soft tissue sarcoma and to improve survival.

[Three cases of renal cell carcinoma metastasizing to the head and neck].

Renal cell carcinoma (RCC) tends to metastasize hematogenously, although metastasis to the head and neck is rare. We report 3 cases of RCC head and neck metastasis within the last 6 years. CASE 1: A 74-yearold woman presented with cervical metastasis from RCC 4 years after right total nephrectomy, involving modified neck dissection. She later had additional surgery and radiation for further distant metastases, survived almost 5 years after the first neck metastasis. CASE 2: A 60-year-old man showed metastatic RCC in the right parotid gland 3 years after right total nephrectomy, involving superficial parotidectomy. CASE 3: A 54-year-old man presented with a metastasis lesion from RCC to the right maxillary sinus 7 years after left total nephrectomy, involving total maxillectomy. Distant metastasis reportedly often occurs long after initial primary RCC treatment. Physicians considering metastatic RCC in differential head and neck diagnosis and resection could conceivably promote better prognosis.

A new combined index of SUVmax of lymph node in PET / CT by a weighting coefficient plus its maximum minor axis in CECT to evaluate occult lymph node metastasis in clinical N0 patients with tongue cancer.

To predict occult nodal metastasis in clinical N0 patients with tongue cancer, we developed combined index (CI) : SUVmax of the largest lymph node in PET / CT by weighting coefficient plus its maximum minor axis (< 10 mm) in contrast-enhanced CT (CECT). In this retrospective study, 57 clinical N0 patients with tongue cancer, who underwent elective supraomohyoid neck dissection at cervical levels of I-III were enrolled. The cutoff value of SUVmax of 2.0 obtained using receiver operating characteristic (ROC) analysis predicted the postoperative positive cervical levels containing metastatic lymph nodes from clinical N0 cervical levels in tongue cancer patients with a sensitivity of 54.5% and a specificity of 78.2%. The cutoff value of CI with weighting coefficient of 1.5 obtained using ROC analysis was 9.8 at the maximum area under the curve of 0.750. The cutoff value of 9.8 predicted the postoperative positive cervical levels containing metastatic lymph nodes from clinical N0 cervical levels in tongue cancer patients with a sensitivity of 68.2% and a specificity of 81.5%. These findings suggest that CI of functional PET / CT and morphological CECT components might improve the diagnostic performance of occult nodal metastasis to select clinical N0 patients with tongue cancer preferable for elective neck dissection. J. Med. Invest. 68 : 154-158, February, 2021.

Radiation Therapy Alone for Human Papillomavirus-Related Squamous Cell Carcinoma of the Oropharynx: A Single-Arm, Phase 2 Study.

PURPOSE: Human papillomavirus (HPV)-related squamous cell carcinoma of the oropharynx (OPSCC) is extremely radiosensitive. Radiation therapy plus high-dose cisplatin remains the standard of care but causes long-term toxicity. Treatment deintensification approaches that reduce toxicity while maintaining survival are desirable for HPV-related OPSCC. METHODS AND MATERIALS: We conducted a single-arm, multicenter, phase 2 trial. Patients with newly diagnosed, biopsy-proven, American Joint Committee on Cancer (seventh edition) stage III or IV OPSCC positive for both p16 and HPV DNA were eligible. Patients with T4, N3, or T1N1 disease were excluded. Smoking history was not included in eligibility criteria. Patients received intensity modulated radiation therapy (IMRT) of 70 Gy in 35 fractions or 70.4 Gy in 32 fractions without chemotherapy. The primary endpoint was complete response or complete metabolic response 10 weeks after IMRT completion. RESULTS: Between September 13, 2013, and November 15, 2016, 39 patients were enrolled according to a 2-stage Simon design. Twenty-three patients (59%) had smoked for more than10 pack-years. Thirty-six patients (92%) had tumors genotyped as HPV16. Thirty-seven patients (95%) received full-dose radiation therapy and 35 (90%) had complete response or complete metabolic response. Median follow-up was 51 months (interquartile range, 41-63 months). One patient (3%) had regional recurrence and 3 (8%) had distant metastasis. One patient died of disease. The 2-year progression-free survival rate was 94% (95% CI, 81%-99%), and the 2-year overall survival rate was 100%. Common grade 3 adverse events during IMRT included mucositis in 10 patients (26%) and dysphagia in 7 patients (18%). No patients were dependent on a feeding tube at 1 month after IMRT completion. No grade 3 or 4 late adverse events were observed. CONCLUSIONS: IMRT alone is associated with excellent response as well as reduced toxicity and could be a treatment option for carefully selected patients with locally advanced "true" HPV-related OPSCC. Further studies are warranted.

[Complications and clinical outcome of salvage surgery after concurrent chemoradiotherapy for advanced head and neck squamous cell carcinoma].

Concurrent chemoradiotherapy (CCRT) is increasingly used in organ preservation for head and neck squamous cell carcinoma (HNSCC), with surgery as second-line treatment for salvaging locoregional failure. The significance of post-CCRT salvage surgery, however, remains to be established. We report complications and clinical outcome in 34 salvage surgeries on 30 subjects with advanced HNSCC treated by docetaxel and cisplatin concurrent with conventional radiotherapy. Postoperative complications occurred in 9 (30%) subjects and 10 (29%) surgeries. There was no significant difference in complication incidence between salvage surgeries for persistent disease (7 of 19 cases, 37%) and those for recurrent disease (3 of 15 cases, 20%). Complication incidence in isolated neck dissection (6 of 21 cases, 29%) did not differ significantly from that in primary site resection (4 of 13 cases, 31%). Most frequent complications were dysphagia and skin flap necrosis, occurring in 5 subjects each. Three with dysphagia underwent percutaneous endoscopic gastrostomy, and two with skin flap necrosis led to pharyngocutaneous fistula, requiring pectoralis major myocutaneous flap repair. No carotid artery rupture or chyle fistula occurred. Overall 3-year survival after salvage surgery was 74% for persistent disease, and 87% for recurrent disease. Although post-CCRT salvage surgery harbors high risk of complication, it renders good survival and is recommendable for all whose disease is operable.

Death unrelated to cancer and death from aspiration pneumonia after definitive radiotherapy for head and neck cancer.

BACKGROUND AND PURPOSE: The incidence of hypopharyngeal and supraglottic cancer (HSC) is high in Japan. This study aimed to retrospectively identify risk factors for death unrelated to cancer and death from aspiration pneumonia after definitive radiotherapy (RT) for HSC. MATERIALS AND METHODS: Overall, 391 patients who began definitive RT for HSC between 2006 and 2014 were identified from the Osaka International Cancer Institute electronic database. Among 391 patients, 33 had a history of surgery for esophageal cancer (EC) and 19 received simultaneous RT for synchronous EC. The cause of death was divided into 3 main categories: "cancer under study," "other malignancy," and "unrelated to cancer." Cox proportional hazard model was used to estimate the hazard ratio (HR). RESULTS: The median follow-up for survivors was 8 (range 3.6-14.1) years. At the last follow-up, 202 patients died. Death from "cancer under study," "other malignancy," and "unrelated to cancer" occurred in 92 (45.5%), 55 (27.2%), and 55 (27.2%) patients, respectively. Twelve patients died from aspiration pneumonia. In multivariate analysis for death unrelated to cancer and death from aspiration pneumonia, history of surgery for EC (HR: 3.87, p < 0.001; HR: 6.84, p = 0.007, respectively) and simultaneous RT for synchronous EC (HR: 3.74, p = 0.006; HR: 16.37, p < 0.001, respectively) were significant risk factors. CONCLUSION: The laryngeal preservation approach by RT for HSC patients with a history of surgery for EC and simultaneous RT for synchronous EC should be used with caution.

Cytoplasmic and serum galectin-3 in diagnosis of thyroid malignancies.

In order to address whether galectin-3 in the sera and fine needle aspirates serve as a diagnostic marker distinguishing between benign and malignant thyroid nodules, we developed an enzyme-linked immunosorbent assay. We quantified galectin-3 in fine needle aspirates from a series of 118 patients with thyroid nodules and serum galectin-3 from another series of 46 patients, which were compared with final histology after thyroidectomy. Relative galectin-3 value (ng/mg), defined as galectin-3 concentration (ng/ml) divided by total protein concentration (mg/ml) in fine needle aspirates, was significantly higher in papillary carcinoma than in the other thyroid entities. There was no significant difference in serum galectin-3 level among patients with thyroid nodules and healthy individuals. Accordingly, relative galectin-3 value allows a definitive diagnosis of papillary carcinoma independent of cellular morphology, whereas serum galectin-3 does not serve as a marker for papillary carcinoma.

[Clinical analysis of cervical lymph node metastasis from an unknown primary carcinoma].

We retrospectively evaluated the efficacy of neck dissection followed by radiotherapy by using the clinical outcome in 15 patients (median age: 60 years) with upper cervical lymph node (level II) metastasis from unknown primary carcinoma undergoing curative treatment from 1999 to 2007. The male-to-female ratio was 4 : 1, and the histopathological diagnosis in 11 patients (73.3%) was squamous cell carcinoma. Clinical N status was distributed as follows: N1, 1; N2a, 4; N2b, 8; and N2c, 2. Of the 15 patients, 13 patients (86.7%) underwent neck dissection and 11 (84.6%), including 2 unresectable cases undergoing concurrent chemoradiotherapy using DOC and CDDP making their condition resectable, underwent neck dissection combined with radiotherapy. Follow-up was from 5 to 72 months (median: 39 months). In 2 of 6 patients, we detected the primary site at the ipsilateral tonsil through tonsillectomy conducted concurrently with neck dissection. Overall 5-year survival determined by the Kaplan-Meier method was 88.9%, and only 1 patient died of metastasis without achieving complete response 29 months after initial treatment. None of the 15 was observed to have local regional recurrence or distant metastasis after initial treatment. These results indicate that neck dissection followed by radiotherapy is recommended for improving the outcome of patients with cervical lymph node metastasis from an unknown primary carcinoma.