Hitoshi Hirakawa

Intraoperative diagnosis of cancer metastasis in sentinel lymph node of oral cancer patients

Sentinel lymph node (SLN) biopsy in the head and neck region is attracting attention. If intraoperative frozen section and/or cytology of SLN is available, one can select an appropriate patient who must undergo neck dissection in a one-stage procedure. We began intraoperative diagnosis of SLN biopsy in patients who underwent oral cancer surgery in 2003. From August 2003 to December 2006, 44 previously untreated patients were accumulated. All patients underwent SLN biopsy prior to the resection of primary cancer. Intraoperative diagnosis of SLN biopsy was performed by multislice frozen section analysis. Patients with positive SLN underwent immediate neck dissection in the same session. Imprint cytology specimen was prepared at the same time. The results of frozen section analysis and imprint cytology were compared with postoperative pathologic diagnosis of permanent specimens. The sensitivity, specificity, overall accuracy, positive and negative predictive value of intraoperative multislice frozen section analysis in lymph node basis were 90.9%, 100%, 99.1%, 100% and 99.0%, respectively. On the other hand, the indexes of imprint cytology were 27.3%, 99.0%, 92.0%, 75.0% and 92.6%, respectively. All indexes of intraoperative frozen section analysis were superior to imprint cytology. In our experience, multislice frozen section analysis surpasses imprint cytology in intraoperative diagnosis of SLN biopsy.

Complete Response to Trastuzumab-Based Chemotherapy in a Patient with Human Epidermal Growth Factor Receptor-2-Positive Metastatic Salivary Duct Carcinoma ex Pleomorphic Adenoma

Introduction: Carcinoma ex pleomorphic adenoma (CXPA) of the salivary glands has often a salivary duct carcinoma (SDC) component, which resembles ductal carcinoma of the breast and frequently overexpresses human epidermal growth factor receptor-2 (HER2). We report a case of metastatic CXPA with SDC component who was treated with trastuzumab-based chemotherapy and has had a durable complete response. Case Report: A 74-year-old man was diagnosed with CXPA of the right parotid gland. The resected tumor was histologically diagnosed as CXPA with a predominant SDC component that showed strong positivity for HER2 protein and HER2 gene amplification. Multiple pulmonary metastatic lesions were detected after surgery, and combination chemotherapy with paclitaxel and trastuzumab was initiated. A complete response was confirmed after 7 treatment cycles, and no evidence of disease progression has been observed after 13 months of initiation of therapy. Conclusions: This report suggests a potential utility of trastuzumab-based chemotherapy for HER2-positive CXPA.

Follow-up after intraoperative sentinel node biopsy of N0 neck oral cancer patients

The objective of the study was to evaluate the validity of sentinel node (SN) biopsy in early oral cancer patients focusing on the accuracy of intraoperative diagnoses of SN status, recurrences in follow-up and impact on patient survival. Previously untreated N0 oral cancer patients were candidates for the study. Using a radioisotope method, an intraoperative SN biopsy was performed. Patients with a positive frozen section of SN underwent immediate neck dissection as a single-stage procedure; they were followed in our outpatient clinic. Forty-five cT1-2N0 patients with squamous cell carcinoma were analyzed. There were seven patients with positive SN, five of whom were detected by intraoperative frozen section analysis. The sensitivity, specificity and accuracy of the intraoperative frozen section analysis of SN were 71.4, 100 and 95.6%, respectively. There were 13 recurrences in the course of all patients treated. Those with positive SN showed a tendency toward recurrence. Three patients with negative SN suffered from delayed ipsilateral neck recurrence. These were considered false negatives at a rate of 7.9%. The 5-year overall survival rate of all patients was 91.1%. SN-positive patient survival was significantly poorer than that of SN-negative patients. Positive SN had a negative impact on the survival. SN biopsy was shown to be a valuable method for determining the neck status of early oral cancer patients. The concordance rate of intraoperative multislice frozen section analysis of SN and patient neck status at the time of operation was 95.6%. SN-positive patients exhibited a tendency toward cancer recurrence. There were three cases of false negatives not conforming to the SN concept and their rate was 7.9%. Positive SN had a negative impact on patient survival.

Survival impact of pulmonary metastasectomy for patients with head and neck cancer.

The purpose of this study was to evaluate the survival impact and prognostic factors of pulmonary metastasectomy in patients with pulmonary metastasis from head and neck cancer.

Prognostic factors and outcomes for salvage surgery in patients with recurrent squamous cell carcinoma of the tongue

Recurrence rates of oral cancer following primary treatment have been reported in the range of 25–48%. However, salvage therapy remains a critical challenge to improving outcomes. Here, we investigated prognostic factors and outcomes for salvage surgery in patients with recurrent oral tongue squamous cell carcinoma (OTSCC).

Clinical results of definitive intensity-modulated radiation therapy for oropharyngeal cancer: retrospective analysis of treatment efficacy and safety

OBJECTIVE To evaluate the clinical outcomes of intensity-modulated radiotherapy for patients with oropharyngeal carcinoma. METHODS Ninety-three oropharyngeal carcinoma patients histopathologically diagnosed with squamous cell carcinoma and treated with definitive intensity-modulated radiotherapy using helical tomotherapy between January 2006 and December 2013 were analyzed. Planning target volume primary and involved nodes was delivered 66-70 Gy at 2 Gy per fraction, while planning target volume prophylactic was delivered 54 Gy using the simultaneous integrated boost technique. RESULTS The median follow-up period among the surviving patients was 40 months (range, 13-96). There were 76 males and 17 females with a median age of 60 years (range, 34-80). The disease was Stage II in 13%, Stage III in 10% and Stage IV in 77% of patients. Ninety-two patients received chemotherapy (99%); 68 patients received induction chemotherapy (73%), while 21 received concurrent chemotherapy (23%). The 3-year overall survival, progression-free survival and locoregional control rates were 80, 68 and 79%, respectively. Multivariate analysis identified an advanced T-category (T3-4), having double cancer, and smoking habit as significantly unfavorable factors for overall survival, progression-free survival and both progression-free survival and locoregional control, respectively. Only two patients who achieved disease control required percutaneous endoscopic gastrostomy tubes in the last follow-up. The rate of Grade 2 xerostomia at 2 years was 23%. CONCLUSIONS Intensity-modulated radiotherapy using helical tomotherapy for patients with oropharyngeal carcinoma provided not only sufficient efficacy, but also preserved parotid function.

Prognostic impact of pathological response to neoadjuvant chemotherapy followed by definitive surgery in sinonasal squamous cell carcinoma

The significance of neoadjuvant chemotherapy followed by definitive surgery for sinonasal squamous cell carcinoma (SCC) was investigated using surgical specimens.

Selection of Therapeutic Treatment with Alternating Chemoradiotherapy for Larynx Preservation in Laryngeal Carcinoma Patients

OBJECTIVE We analyzed the efficacy of treatments that included alternating chemoradiotherapy in laryngeal cancer patients. METHODS Alternating chemoradiotherapy consisted of chemotherapy with 5-fluorouracil (600 mg/m(2)/day) on Days 1-6 and cisplatin (80 mg/m(2)) on Day 7 followed by radiotherapy with 30 Gy. Additional chemoradiotherapy was administered to responders, and laryngectomy was performed in non-responders. The contribution of alternating chemoradiotherapy to laryngeal preservation was compared with that of radiotherapy in patients with T2 disease and with that of laryngectomy in patients with T3/T4 disease. RESULTS Analysis of 87 patients was conducted. The 5-year overall survival rate of T2 patients (n = 46) was 88.9% for definitive radiotherapy and 82.5% for alternating chemoradiotherapy. The laryngectomy-free rate in T2 patients was 90.5% for definitive radiotherapy and 80.0% for alternating chemoradiotherapy. In patients with T3/T4 disease (n = 41), the 5-year overall survival rate was 86.9% for alternating chemoradiotherapy and 67.4% for laryngectomy. The laryngectomy-free rate in T3/T4 patients was 91.7% for alternating chemoradiotherapy and 0.0% for laryngectomy. CONCLUSIONS In advanced carcinoma of the larynx, alternating chemoradiotherapy treatment might enable larynx preservation.

Clinical Outcome and Patterns of Recurrence of Head and Neck Squamous Cell Carcinoma with a Limited Field of Postoperative Radiotherapy

BACKGROUND Postoperative radiotherapy is the standard treatment for head and neck squamous cell carcinoma having high-risk features in surgical specimens. However, its severe toxicity can be a significant problem. This study was undertaken to evaluate the efficacy of our limited-field postoperative radiotherapy with the aim of reducing morbidity by minimizing the radiation field. METHODS Between 2000 and 2009, 154 patients with head and neck squamous cell carcinoma received limited-field postoperative radiotherapy. The reason for postoperative radiotherapy was close/positive margins in 33 patients and extracapsular extension in 91. The median radiation dose was 50 Gy (30-66.4). The radiation field covered the tumor bed without lymph node regions for close/positive margins and only involved sites of the neck region were irradiated for multiple nodes or extracapsular extension. RESULTS With a median follow-up of 43 months for surviving patients, the 3-year overall survival and progression-free survival rates were 53.7 and 42.1%, respectively. The 3-year rates of progression-free survival of the group having major risks (i.e. close/positive margins and/or extracapsular extension) and the group with other risks were 34.7 and 62.8%, respectively (P < 0.01). Thirty-one local recurrences (20%), of which 22 were located out-of-field, and 44 regional recurrences (29%), of which 16 were located out-of-field, developed. Late toxicity of grade 3 or greater developed in only six patients (3.8%). CONCLUSIONS Although the toxicities associated with limited-field postoperative radiotherapy could be kept to lower levels, the locoregional control rate did not seem to be sufficient. We should arrange the radiation field depending on risk factors.

Impact of positron emission tomography with the use of fluorodeoxyglucose on response to induction chemotherapy in patients with oropharyngeal and hypopharyngeal squamous cell carcinoma.

Abstract Conclusion: Maximum standardized uptake values (SUVmax) have prognostic value for induction chemotherapy (ICT) response and survival in oropharyngeal and hypopharyngeal squamous cell carcinoma (OHSCC) patients. Pretreatment positron emission tomography with the use of fluorodeoxyglucose (18F-FDG PET) may be an aid in deciding the treatment strategy in OHSCC patients. Objectives: We investigated the association between pretreatment 18F-FDG PET and response to ICT and survival in OHSCC patients. Methods: We conducted a retrospective cohort study of 58 OHSCC patients treated at Aichi Cancer Center Hospital. The predictive impact of SUVmax of the primary tumor site was evaluated using statistical multivariate proportional hazard models. Results: Thirty-one cases (53%) were located in the oropharynx and 27 (47%) in the hypopharynx. Median SUVmax was 11.6 (range 3.2–23.5), and was significantly higher in the 8 patients with less than stable disease than in the 50 with more than partial response (median SUVmax, 17.3 vs 11.1; p = 0.002). In multivariate analysis, hazard ratios for the medium and high SUVmax groups relative to the low group were 3.07 (95% confidence interval, 0.62–15.29; p = 0.170) and 4.71 (0.97–22.89; p = 0.055), respectively, and the dose-response relationship was statistically significant (p trend = 0.047). A similar tendency was observed on subclassification by oropharynx and hypopharynx.