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.

Retroauricular Hairline Incision for Parotidectomy.

An S-shaped incision is most frequently used for surgeries on benign parotid gland tumors. Surgical procedures using a retroauricular hairline incision (RAHI) for parotid gland tumors was first reported in 2009, but no such case has been reported from Japan. Because RAHI leaves no trace of visible scarring in the face and neck, it is more favorable in terms of cosmetics than an S-shaped incision. We operated on 25 cases of benign parotid gland tumors using RAHI between February 2012 and June 2014. In this report, we give a detailed description of the RAHI procedure, and quantify and compare operative time, bleeding, and complication rate between RAHI procedure and conventional methods. 　The mean operative time was 150.2 min. Permanent facial paralysis was observed any RAHI case. However, transient facial paralysis was seen in 20.0% RAHI cases, and this value is similar to data reported previously. Because RAHI does not require a preauricular skin incision, unlike S-shaped and facelift incisions, it is difficult to gain an anterosuperior view of the parotid gland. In other words, tumors in the lower pole of the superficial lobe of the parotid gland are the best indication for RAHI. 　RAHI is a useful approach when performed by surgeons with sufficient experience with standard methods and when surgical indications are accurately determined.

[Resection of nasopharyngeal mucoepidermoid carcinoma using the maxillary swing approach].

Mucoepidermoid carcinomas (MECs) are a common neoplasm of the minor salivary glands. However, nasopharyngeal MECs are an extremely rare entity. We describe herein our experience in the resection of a nasopharyngeal MEC using the maxillary swing approach (MSA). A 42-year-old man was referred to our institute complaining of a feeling of fullness in his left ear. The tumor was found to localized in the nasopharynx. The ragiological findings showed a solid, 30 x 27 x 26mm tumor lying on the lateral wall of the nasopharynx. The histological examination revealed MEC. The tumor was removed with maxillary swing approach. The patient has remained free from recurrence for 2 years and 7 months after surgery. There are many reports to recommend surgery-based treatment for MECs of the head and neck region. It is moreover thought that nasopharyngeal MECs are no exception. To our knowledge, only 7 cases of MEC of the nasopharynx have been reported in Japan. From our experience, the MSA is one of the useful approaches to achieve minimum facial deformity and maxillary dysfunction. We discuss the etiology with a review of the literature.

[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.

[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.

Modified TPEx as First-line Treatment for Recurrent and/or Metastatic Head and Neck Cancer.

BACKGROUND/AIM: To retrospectively evaluate the efficacy and safety of modified TPEx (docetaxel 60 mg/m2 on day 1, cisplatin 60 mg/m2 on day 1, and weekly cetuximab 250 mg/m2 with loading dose of 400 mg/m2) followed by maintenance cetuximab as first-line treatment for inoperable recurrent and/or metastatic squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: We analyzed 22 Japanese patients receiving modified TPEx every 21 days for four cycles with or without prophylactic granulocyte colony-stimulating factor (G-CSF). RESULTS: The best overall response rate was 55% [95% confidence interval (CI)=35-73]. The median progression-free survival and overall survival were 8.9 months (95%CI=3.9-10.2) and 14.3 months (95%CI=10.1-28.2), respectively. Without prophylactic G-CSF, Grade 3/4 neutropenia and febrile neutropenia was common (94% versus 20%; p=0.003 and 41% versus 0%; p=0.11, respectively). CONCLUSION: The modified TPEx is effective, while prophylactic G-CSF is essential.

[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.

Prognostic Value of FDG-PET in patients with oropharyngeal carcinoma treated with concurrent chemoradiotherapy.

PURPOSE: The purpose of this study was to evaluate the predictive value of 2-deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography (FDG-PET) following concurrent chemoradiotherapy (CRT) on survival in patients with carcinoma of the oropharynx (OPC). METHODS: Eighteen patients with primary OPC who underwent PET pre- and post-CRT were evaluated prospectively for survival. The prognostic performance of post-CRT PET and CT for recurrence was compared. RESULTS: Patients with positive post-CRT PET exhibited significantly lower 2-year cause-specific survival and disease-free survival (50% vs. 91%, P < 0.05 and 0% vs. 83%, P < 0.0001); however, patients with positive post-CRT CT did not exhibit any significant difference (67% vs. 83%, P = 0.416 and 50% vs. 75%, P = 0.070). Other factors, such as clinical and pre-CRT PET variables, also did not indicate any significant difference. The accuracy of prediction of residual and local recurrence for post-CRT PET and CT (local%/regional%) was 83%/94% and 83%/78%, respectively. CONCLUSION: OPC patients with positive post-CRT PET exhibit poor survival. The prognostic accuracy of post-CRT PET is superior to that of CT. The results of post-CRT FDG-PET should be included in the management of the OPC patients.

[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.

The resected area of the posterior wall of the external auditory canal during transcanal endoscopic ear surgery for cholesteatoma.

OBJECTIVE: The aim of this study was to evaluate part of the area of the posterior wall of the external auditory canal (EAC) that is resected during transcanal endoscopic ear surgery (TEES) for cholesteatomas that extend to the mastoid cavity, and to determine whether TEES is a minimally invasive surgical procedure for cholesteatoma. METHODS: This was a retrospective study involving 25 patients with cholesteatoma that extended to the mastoid cavity, and who underwent surgery between October 2014 and October 2015. The patients' cholesteatomas were removed using TEES. In this procedure, the superoposterior wall of the EAC was resected in order to access the deepest part of the cholesteatoma. We made a paper template by tracing the shape of the resected EAC and then reconstructed the resultant defect with a piece of cartilage, the size of which was based on the size of the template. We evaluated the size and greatest dimension of the resected part of the EAC by measuring the template. Preoperatively, we also evaluated the volume of each cholesteatoma on computed tomography (CT) images. RESULTS: The median size of the resected region was 37.3 (14.7-68.4)mm2. The median length of the greatest dimension of the resected area was 8.7 (5.1-15.9)mm. The median cholesteatoma volume was 417 (43-1399)mm3. The correlation coefficient (R2) obtained using a two-thirds order approximation curve for the relationship between the resected tissue area and the cholesteatoma volume (0.617) was higher than that obtained by linear approximation (0.387). CONCLUSION: These results suggest that the resected area was minimal and of an appropriate size relative to the volume of the cholesteatoma.

Phase 2 study of docetaxel, cisplatin, and concurrent radiation for technically resectable stage III-IV squamous cell carcinoma of the head and neck.

PURPOSE: We investigated the efficacy and safety of weekly low-dose docetaxel and cisplatin therapy concurrent with conventionally fractionated radiation in patients with technically resectable stage III-IV squamous cell carcinoma of the head and neck. METHODS AND MATERIALS: Between March 2004 and October 2011, we enrolled 117 patients, of whom 116 were analyzable (43 had oropharyngeal cancer, 54 had hypopharyngeal cancer, and 19 had laryngeal cancer), and 85 (73%) had stage IV disease. Radiation consisted of 66 Gy in 33 fractions. Docetaxel, 10 mg/m(2), followed by cisplatin, 20 mg/m(2), administered on the same day were given once a week for 6 cycles. The primary endpoint was overall complete response (CR) rate after chemoradiation therapy. Human papillomavirus (HPV) DNA in oropharyngeal cancer was examined by PCR. RESULTS: Of 116 patients, 82 (71%) completed treatment per protocol; 102 (88%) received the full radiation therapy dose; and 90 (78%) and 12 (10%) patients received 6 and 5 chemotherapy cycles, respectively. Overall CR rate was 71%. After median follow-up of 50.9 months (range: 15.6-113.9 months for surviving patients), 2-year and 4-year overall survival rates were 82% and 68%, respectively. Cumulative 2-year and 4-year local failure rates were 27% and 28%, respectively, whereas distant metastasis rates were 15% and 22%, respectively. HPV status in oropharyngeal cancer was not associated with treatment efficacy. Acute toxicity included grade 3 and 4 in-field mucositis in 73% and 5% of patients, respectively, whereas myelosuppression and renal injury were minimal. No patients died of toxicity. Feeding tube dependence in 8% and tracheostomy in 1% of patients were evident at 2 years postchemoradiation therapy in patients who survived without local treatment failure. CONCLUSIONS: Local control and survival with this regimen were satisfactory. Although acute toxicity, such as mucositis, was common, late toxicity, such as laryngoesophageal dysfunction, was minimal. Therapy using weekly low-dose docetaxel and cisplatin concurrent with radiation warrants further evaluation.

[A clinical study of 104 patients with tongue cancer and the relationship between DNA ploidy and prognosis in 41 cases].

One-hundred and four patients with previously untreated tongue cancer seen in our department between 1986 and 1998 were enrolled in a clinical study. The DNA ploidy patterns observed in fresh frozen specimens obtained from 41 patients were analyzed, and prognostic factors were investigated. According to the TNM classification (UICC 1997), 43 patients had stage I tumors, 29 had stage II tumors, 17 had stage III tumors, and 15 had stage IV tumors. The 5-year cause-specific survival rates for each stage were 94.7%, 64.4%, 50.0% and 45.7%, respectively. The most frequent cause of death associated with the original disease was the recurrence of the disease in cervical lymph nodes (19/27, 70.4%). The occurrence of late cervical metastasis was high among patients with a T2N0 disease. Patients with stage II disease should undergo elective neck dissection or be carefully monitored using ultrasonography. Among the 41 cases in which the DNA ploidy pattern was analyzed, diploid patterns were found in 30 cases and aneuploid patterns were found in 11. The 5-year cause-specific survival rate and the 5-year locoregional control rate were significantly lower for the aneuploid cases (18.2%, 38.9%) than for the diploid cases (66.5%, 69.8%) (p = 0.0003, p = 0.0339). The incidence of distant metastasis was significantly higher among the aneuploid cases (6/11, 54.5%) than among the diploid cases (3/30, 10.0%) (p = 0.0058). The ploidy pattern, as determined by flow cytometric DNA analysis, may reflect the malignancy grade of tongue cancers.

Impact of FDG-PET on prediction of clinical outcome after concurrent chemoradiotherapy in hypopharyngeal carcinoma.

PURPOSE: To evaluate prognostic value of pretreatment and posttreatment 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET) in advanced hypopharyngeal carcinoma treated by chemoradiotherapy. PROCEDURES: Thirty-one patients underwent a baseline FDG-PET and then FDG-PET was repeated 7 weeks after chemoradiotherapy. Primary tumor uptake of FDG, measured as the maximal standardized uptake value (SUV(max)), was analyzed in relation to local control and survival. RESULTS: Neither local control nor cause-specific survival were associated with pretreatment SUV(max). In contrast, patients with a high posttreatment SUV(max) had significantly poorer local control (P = 0.002), as well as poorer cause-specific survival (P = 0.0075), compared to those with a low posttreatment SUV(max). This prognostic significance of posttreatment SUV(max) remained when only a subset of patients showing local complete response to chemoradiotherapy was analyzed. CONCLUSIONS: Posttreatment FDG uptake represents an independent prognostic factor for hypopharyngeal carcinoma treated by chemoradiotherapy. Patients with a high posttreatment FDG uptake may benefit from adjuvant chemotherapy.

The role of CT and ¹8F-FDG PET in managing the neck in node-positive head and neck cancer after chemoradiotherapy.

CONCLUSION: Patients showing a complete response on computed tomography (CT) can be spared from neck dissection. OBJECTIVE: To determine whether CT or fluorine-18-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) is superior in the evaluation of persistent nodal disease after chemoradiotherapy in patients with node-positive head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Study entry criteria included node-positive HNSCC treated with definitive chemoradiotherapy, a local complete response, and post-treatment CT and (18)F-FDG PET studies 7 weeks after chemoradiotherapy. Forty-eight patients with 60 node-positive necks were eligible. Nodes larger than 1 cm, or with central necrosis on CT, or any visually hypermetabolic nodes on (18)F-FDG PET were considered positive. Regardless of PET findings, necks with positive CT were subjected to neck dissection, whereas those with negative CT were observed without neck dissection. RESULTS: Twenty-two necks showed positive CT, 20 and 2 of which underwent neck dissection and fine needle aspiration cytology, respectively, resulting in pathologic evidence of persistent nodal disease in 13 necks. Five of 38 necks with negative CT developed regional recurrence. Diagnostic accuracy was equivalent between CT and (18)F-FDG PET. There was no difference in 3-year cause-specific survival between patients with positive and negative CT (79% and 81%, respectively).

The role of fine-needle aspiration cytology and magnetic resonance imaging in the management of parotid mass lesions.

CONCLUSION: Fine-needle aspiration cytology (FNAC) is the diagnostic modality of first choice for characterization of parotid mass lesions, while magnetic resonance imaging (MRI) should not be requested routinely. MRI can be reserved until FNAC shows the indication for surgical intervention. OBJECTIVES: Although both FNAC and MRI are useful preoperative diagnostic modalities for parotid mass lesions, it is not well established which modality is more effective. In the present study we sought to address the relative value of FNAC and MRI in relation to the differential diagnosis of benign and malignant parotid mass lesions. SUBJECTS AND METHODS: Eighty-one patients with parotid mass lesions (60 benign and 21 malignant) who had preoperatively undergone FNAC and MRI were reviewed retrospectively. RESULTS: Unsharp margin and infiltration into adjacent tissues on MRI significantly correlated with a malignant histology. The sensitivity/specificity/accuracy of FNAC and MRI were 90%/95%/94% and 81%/92%/89%, respectively. Either FNAC or MRI served equally to predict the malignant nature of parotid mass lesions. Furthermore, the combination of FNAC and MRI yielded no diagnostic advantage over either modality alone. Accurate histological typing rates by FNAC were 80% and 62% for benign and malignant lesions, respectively.