Tohru Furusaka

Long-term observations and salvage operations on patients with T2N0M0 squamous cell carcinoma of the glottic larynx treated with radiation therapy alone

Abstract Conclusion: A long-term study was carried out on 57 patients treated with radiation alone who had T2N0M0 squamous cell carcinoma of the glottic larynx. The response and survival rates were satisfactory, but the complete response (CR) and the larynx preservation rates showed a need for improvement. Thirty-four patients underwent salvage operations and a safe margin for the partial laryngectomy was evaluated by histopathological examination of serial sections of the surgical specimen. Objective: Although the effectiveness of combined chemoradiation therapy in the treatment of head and neck cancer has been reported, the facts remain unclear. The purpose of this study was to analyze the long-term outcomes of radiation therapy alone for T2N0M0 squamous cell carcinoma of the glottic larynx, i.e. the survival rate, the larynx preservation rate, and the reality of salvage operations. This is expected to contribute to an understanding of the synergistic effects of anticancer drugs used in combined chemoradiation therapy, the use of which will be expanded in the future. The reason for this is that the radiation source, radiation field, and radiation dose are nearly identical for patients with T2N0M0 squamous cell carcinoma of the glottic larynx. Methods: The subjects were 57 patients with untreated T2N0M0 squamous cell carcinoma of the glottic larynx. There were 55 males and 2 females. Their ages ranged from 31 to 86 years. The 4 MV Liniac X-ray external beam radiation therapy was carried out via two-dimensional horizontal opposing ports, 2 Gy per dose, five times a week with a total of 66 Gy. Results: In 57 patients, we observed CR in 33 patients, partial response (PR) in 20 patients, no change (NC) in 4 patients, and progression disease (PD) in none of the patients. The response rate was 93.0% and the CR rate was 57.9%. The survival rates (Kaplan–Meier method) were: 5-year survival rate of 88.5% and 10-year survival rate of 73.5%. The larynx preservation rates (Kaplan–Meier method) were: 5-year larynx preservation rate of 60.4% and 10-year larynx preservation rate of 50.1%. The main side effect of grade 3 or more was only stomatitis in four patients, all of which were reversible changes (CTCAT v3.0 JCOG/JSCO). Salvage operation was required in 34 (59.6%) of 57 patients, 10 patients underwent partial laryngectomy, total laryngectomy was performed in 3 of the 10 patients following the partial laryngectomy, and 27 patients (47.4%) underwent total laryngectomy. The surgical specimens were serially sectioned at a thickness of 4 μm and examined histopathologically and compared to the macroscopic findings at surgery. The safe margin for partial laryngectomy was considered grossly to be 5 mm from the edge of the tumor.

Superselective intra-arterial chemoradiation therapy for functional laryngeal preservation in advanced squamous cell carcinoma of the glottic larynx

Abstract Conclusion: Superselective intra-arterial chemotherapy is a safe and useful treatment that preserves the vocal, swallowing, and feeding functions of the larynx in T3 cancer supplied by the superior laryngeal artery and T4a cancer not extending beyond the thyroid cartilage. Objective: To evaluate the outcomes of superselective intra-arterial chemotherapy for squamous cell carcinoma of the glottic larynx. Methods: Sixty-four patients with squamous cell carcinoma of the glottic larynx underwent treatment of the primary tumor using induction chemotherapy with two cycles of intra-arterial docetaxel and cisplatin, plus continuous intravenous infusion of 5-fluorouracil for 120 h starting on day 2; followed by two cycles of concurrent chemoradiation therapy. Residual neck lymph node metastases were treated by neck dissection. Results: The overall 5- and 10-year survival rates were 70.4% and 62.9%, respectively. The 5- and 10-year survival rates were 96.3% and 89.9%, respectively, in the 29 patients with T3 cancer, and 50.4% and 44.1%, respectively, in the 35 patients with T4a cancer. The overall 5- and 10-year laryngeal preservation rates were 71.0% and 60.6%, respectively. The 5- and 10-year laryngeal preservation rates were 92.5% and 87.4%, respectively, in patients with T3 cancer, and 48.6% and 35.6%, respectively in patients with T4a cancer. No irreversible adverse effects were reported.

Efficacy of multidrug superselective intra-arterial chemotherapy (docetaxel, cisplatin, and 5-fluorouracil) using the Seldinger technique for tongue cancer

Abstract Conclusion: This therapy produced better results than intravenous multidrug chemotherapy (CF therapy, CPF therapy, etc.) or superselective intra-arterial chemotherapy (SIC) alone with cisplatin (CDDP) and 5-fluorouracil (5-FU). Primary tumor may be controlled by SIC alone in cases of T2 and many cases of T3 tumors, and by the combination of SIC and concurrent radiotherapy in cases of T3 and many cases of T4a. Cervical lymph node metastasis was treated with neck dissection in some patients. The results indicate that this therapy is useful to control primary tumor without resection for organ preservation. Objectives: This therapy was intended to control primary tumor without resection for better quality of life (QOL). Methods: A total of 45 patients with primary squamous cell carcinoma of the tongue were included in the study. SIC with docetaxel, cisplatin, and 5-FU was administered. Results: In terms of the primary response of primary tumor, 43 patients achieved a clinical complete response (CR). Moreover, in these patients no cancer cells were histopathologically found by biopsy, resulting in a response rate of 100% and a CR rate of 95.6%. During the median follow-up period of 1779 days (59 months) (range 110–3752 days), the 5-year survival rate and organ preservation rate were 89.8% and 80.7%, respectively.

Long-term follow-up and salvage surgery in patients with T2N0M0 squamous cell carcinoma of the glottic larynx following concurrent chemoradiation therapy with cisplatin and 5-fluorouracil for laryngeal preservation

Abstract Conclusion: Patients who received concurrent chemoradiation therapy or radiation therapy alone were followed over a long term. The complete response (CR), 10-year survival, and 10-year larynx preservation rates were 87.5%, 95.3%, and 75.1%, respectively. Statistically, concurrent chemoradiation therapy contributes to laryngeal preservation but not to the survival rate. Objective: To determine the additive and synergistic effects of anticancer chemotherapy combined with chemoradiation therapy for squamous cell carcinoma (SCC) of the glottic larynx. Methods: Eighty-nine patients with untreated T2N0M0 SCC of the glottic larynx were included. Thirty-two patients received treatment cycles consisting of intravenous cisplatin (CDDP) on day 1 (80 mg/m2) and intravenous 5-fluorouracil (5-FU) over 120 h on days 2–6 (600 mg/m2/day) every 4 weeks. Radiotherapy was delivered by a 4 MV linac X-ray machine at a dose of 66 Gy. Fifty-seven patients received radiotherapy alone. Results: After chemoradiation therapy, the overall response, CR, 10-year survival, and 10-year larynx preservation rates were 100%, 87.5%, 95.3%, and 75.1%, respectively. Side effects included leukopenia, neutropenia, mucositis, and dermatitis. Seven patients (21.9%) required salvage surgery. Pathological findings confirmed that the treatment regimen caused marked cancer tissue degeneration. Histologic examination of surgical specimens suggested that the safety margin for partial laryngectomy was 4 mm from the gross tumor.

Cervical branch of the facial nerve approach for retrograde parotidectomy compared with anterograde parotidectomy

Abstract Conclusion: The cervical branch of the facial nerve approach for parotidectomy is an excellent surgical technique that can reduce the incidence of facial nerve paralysis, surgical time, and surgical blood loss. Objective: To develop and evaluate a surgical technique for parotidectomy that can reduce the incidence of facial nerve paralysis. Methods: Retrograde parotidectomy following identification of the cervical branch of the facial nerve in 90 subjects was compared with standard anterograde parotidectomy in 100 subjects. Results: Retrograde parotidectomy with a cervical branch approach was associated with significant decreases in the incidence of facial nerve paralysis, surgical time, and surgical blood loss, compared with anterograde parotidectomy.

Laryngeal preservation in advanced piriform sinus squamous cell carcinomas using superselective intra-arterial chemoradiation therapy with three agents.

Abstract Conclusion: Superselective intra-arterial chemotherapy, which enables local control and laryngeal preservation, is a safe and useful therapy for preservation of nutrition, speech, and swallowing functions. Objective: To improve the laryngeal preservation rate in patients with hypopharyngeal piriform sinus squamous cell carcinoma by superselective intra-arterial chemotherapy. Methods: Fifty-seven patients received anterograde intra-arterial administration of docetaxel and cisplatin, and two courses of intravenous continuous infusion of 5-fluorouracil as a neoadjuvant chemotherapy over 120 h starting on day 2. Concurrent chemoradiotherapy was administered from the third course to control the primary cancer. Remaining neck lymph node metastases were treated in principle by neck dissection. Results: The 5- and 10-year survival rates were 68.5% and 58.9%, respectively. The 5-year rates by the T classification were 96.0% (10-year rate, 88.6%) in T3, 48.1% in T4a, and 16.7% in T4b. The 5- and 10-year laryngeal preservation rates were 65.2% and 62.4%, respectively. The 5-year rates by the T classification were 92.4% (10-year rate, 87.6%) in T3, 36.2% in T4a, and 16.7% in T4b. No irreversible side effects, complications, or sequelae were reported. Superselective intra-arterial chemotherapy showed superior laryngeal preservation as well as high survival rates, particularly in T3, and was considered a useful therapy.

Superselective intra-arterial chemotherapy for laryngeal preservation in carcinoma of the anterior oropharyngeal wall

Abstract Conclusion: Superselective intra-arterial chemotherapy, which can provide local control and laryngeal preservation, is safe and useful for preserving pharyngeal and laryngeal functions. Objective: To evaluate superselective intra-arterial chemotherapy in terms of the contribution to survival and laryngeal preservation in squamous cell carcinoma (SCC) of the anterior oropharyngeal wall. Methods: A total of 51 patients with SCC of the anterior oropharyngeal wall received intra-arterial administration of docetaxel at 60 mg/m2 and cisplatin at 60 mg/m2 anterogradely, followed by intravenous continuous infusion of 5-fluorouracil at 750 mg/m2/day over 120 h starting on day 2. Neck lymph node metastases were treated by neck dissection. Results: The 5- and 10-year survival rates of the 51 patients were 72.8% and 66.4%, respectively. The 5-year survival rates of patients with T2, T3, T4a, and T4b cancer were 100%, 88.7%, 41.9%, and 33.3%, respectively. The 5- and 10-year laryngeal preservation rates of the 51 patients were 63.4% and 30.0%, respectively. The 5-year laryngeal preservation rates of patients with T2, T3, T4a, and T4b cancer were 100%, 75.2%, 23.6%, and 33.3%, respectively. No irreversible side effects, complications, or sequelae were reported.

Multidrug resistance in mucoepidermoid carcinoma of the parotid gland – immunohistochemical investigations of P-glycoprotein expression

Abstract Conclusion: P-glycoprotein is abundantly expressed in certain parotid mucoepidermoid carcinoma tissues, known historically to be multidrug resistant. This discovery may be important in incrementally advancing our ability to develop alternative pharmacologic strategies to improve multi-modality tumor control. Objective: P-glycoprotein plays a functional role in promoting the efflux of drug metabolites in certain malignant tumors. With this understanding we immunohistochemically investigated the expression of P-glycoprotein in parotid mucoepidermoid carcinoma tissues and examined prognostic factors that contribute to the treatment of parotid cancer. Methods: Thirteen patients with mucoepidermoid carcinoma of the parotid gland were included. P-glycoprotein expression was immunohistochemically investigated by a modified avidin-biotin-peroxidase complex method using four different antibodies. Results: P-glycoprotein expression was observed in a higher percentage of patients with higher grade malignancy. The tumor size-related difference in P-glycoprotein expression was only significant for staining with one antibody, and no significant differences were observed with or without induction chemotherapy.

Long-term follow-up and salvage surgery in patients with T2N0M0 squamous cell carcinoma of the glottic larynx who received concurrent chemoradiation therapy with carboplatin (CBDCA) - AUC 1.5 vs AUC 2.0

Abstract Conclusion: Patients who received concurrent chemoradiation therapy with carboplatin were followed up on a long-term basis. In 25 patients treated with carboplatin at an AUC of 2.0 mg/ml, the complete response (CR), 10-year survival, and 10-year larynx preservation rates were 96.0%, 91.1%, and 75.2%, respectively, and the safety margin for partial laryngectomy was 4 mm from the gross tumor. Objectives: To perform long-term follow-up of the therapeutic outcomes of concurrent chemoradiation therapy and salvage surgery to determine the additive and synergistic effects of anticancer drugs combined with chemoradiotherapy. Methods: Fifty male patients (aged 33–76 years) with untreated T2N0M0 squamous cell carcinoma of the glottic larynx were included. Carboplatin was intravenously administered once a week for 4 weeks. Radiotherapy was delivered by an external beam of 4 MV linac X-ray (total = 66 Gy). Results: The AUC 1.5 combination group showed overall response, CR, 5-year survival, 10-year survival, 5-year larynx preservation, and 10-year larynx preservation rates of 100.0%, 68.0%, 83.4%, 77.0%, 75.2%, and 75.2%, respectively. The AUC 2.0 combination group showed corresponding rates of 100%, 96.0%, 95.7%, 91.1%, 82.9%, and 72.7%, respectively. The most common side effects of grade 3 or more were leukopenia, neutropenia, and mucositis (stomatitis), and all were reversible. Thirteen patients (52.0%) in the AUC 1.5 combination group and nine patients (36.0%) in the AUC 2.0 combination group required salvage surgery. Histologically, concurrent chemoradiation therapy with carboplatin caused more severe cancer tissue degeneration. Pathological examinations indicated that the safety margin for partial laryngectomy was 4 mm from the gross tumor.

Concurrent chemoradiation therapy with docetaxel (DOC) for laryngeal preservation in T2N0M0 glottic squamous cell carcinomas

Abstract Conclusion: Concurrent chemoradiation therapy with docetaxel (DOC) at a dose of 10 mg/m2 twice a week contributed to laryngeal preservation. Objective: To determine laryngeal preservation following concurrent chemoradiation therapy with DOC. Methods: A total of 141 patients with untreated T2N0M0 squamous cell carcinoma of the glottic larynx were included in the study. The treatments were either radiation therapy alone or DOC intravenously administered at a dose of 10 mg/m2 once or twice a week during radiotherapy with 4 MV linac X-ray (total of 66 Gy for 33 days). Results: The response and CR rates were 100% and 90.5% in the once-weekly combination group, and 100% and 97.6% in the twice-weekly combination group, respectively. The 5-year survival rates were 76.8% in the once-weekly combination group and 96.8% in the twice-weekly combination group. The 5-year laryngeal preservation rates were 83.8% in the once-weekly combination group and 97.6% in the twice-weekly combination group. The most common side effects were mucositis, dermatitis, and alopecia. The patients who received DOC twice a week showed more severe cancer tissue degeneration, and pathological examination of serial sections indicated that the safety margin for partial laryngectomy was considered to be 3 mm from the gross tumor with good glottal closure.