To evaluate treatment outcome and to determine optimal treatment strategy for patients with clinically lymph node-negative (N0) oral cavity squamous cell carcinoma (SCC).
Two hundred and twenty-seven patients with oral cavity SCC received radiotherapy with curative intent. We retrospectively analyzed 69 patients with clinically N0 disease. Forty-three patients were treated with surgery followed by radiotherapy (S+EBRT) and 26 with radiotherapy alone (EBRT). The median doses administered were 63.0 Gy for S+EBRT and 70.2 Gy for EBRT.
The rates of occult metastasis were 60% for T1, 69% for T2, 100% for T3 and 39% for T4, respectively, among patients who underwent neck dissection. A contralateral occult metastasis occurred only in two patients. The median follow-up was 39 months (range, 6–170 months). The 5-year overall survival (OS), disease-free survival (DFS), local control (LC) and regional control (RC) rates for all patients were 56, 50, 66 and 79%, respectively. The 5-year OS, DFS, LC and RC rates were 67/39% (P < 0.01), 66/24% (P < 0.01), 87/30% (P < 0.01) and 73/89% (P = 0.11) for S+EBRT/EBRT, respectively.
The risk for occult neck metastasis is high in patients with oral cavity SCC; therefore, elective neck treatment should be considered. Excellent RC for subclinical disease can be achieved with radiotherapy alone. However, external beam radiotherapy alone to primary tumor resulted in poor LC and combined treatment with surgery and radiotherapy appeared to be a better treatment strategy.
Low-dose-rate (LDR) brachytherapy is an effective treatment for tongue cancer. However, little is known about the biological mechanism underlying this therapy, characterized by delivery of continuous exposures of LDR irradiation. It is reported that lower microvessel density (MVD), lower Ki-67 index or higher expression of endogenous hypoxic markers such as carbonic CA IX and Glut-1 are related to the poor control of tumors treated with external irradiation. To elucidate the biological characteristics of LDR brachytherapy, we analyzed our results in cases of tongue cancer treated with LDR brachytherapy by using immunohistochemical stainings with antibodies against Ki-67 and MVD, Glut-1 and CA IX.
The prognostic value of Ki-67 index, MVD and the expression of CA IX and Glut-1 was assessed in 68 tongue cancers treated with LDR brachytherapy. The specimens were taken from tongue cancers before radiation therapy and immunohistochemical staining was performed.
The local recurrence-free survival rates were significantly different between T1+T2 and T3 (P = 0.00067), but not between low and high Ki-67 indexes (P = 0.54), between low and high MVD (P = 0.071), low and high CA IX indexes (P = 0.062) or low and high Glut-1 indexes (P = 0.107). T stage, the size of the tumor was the only significant factor for local control in multivariate analyses (P = 0.0377).
LDR could overcome the radioresistence of non-cycling and hypoxic cells; however, we cannot draw firm conclusions due to the limited number of patients.
Larynx-preserving surgery is frequently performed for advanced hypopharyngeal cancer involving the larynx. However, reconstruction after partial pharyngolaryngectomy (PPL) remains a challenging problem because of the high risk of postoperative aspiration. In this report, we describe our new three-dimensional method for reconstructing supraglottic structures with a radial forearm flap. This is a retrospective analysis of 20 patients who underwent PPL for having hypopharyngeal cancer involving the larynx at our institution from 1996 to 2005.
The resulting pharyngolaryngeal defects were reconstructed with radial forearm flaps in all patients. Three-dimensional structures were reconstructed with a single nylon suture, which was used to hoist the flap and ensures that the arytenoids and the aryepiglottic fold were of appropriate height.
Radial forearm flaps were transferred successfully in all but one case. Swallowing function was satisfactory in all patients, and decannulation could be performed in all but one patient. Postoperative conversational function in all patients was rated as excellent with Hirose's scoring system.
Free jejunum transfer is the method of first choice for reconstruction of a defect after partial hypopharyngectomy. However, the complex supraglottic structures of the larynx are difficult to reconstruct with a free jejunal graft after PPL. In such cases, we perform three-dimensional reconstruction of the pharyngolaryngeal defect with a radial forearm flap and have achieved satisfactory postoperative function. We believe that our new procedure is a useful method for functional reconstruction after PPL.
It is well known that mucoepidermoid carcinoma (MEC) displays a variety of biological behaviors. While the high-grade type is a highly aggressive tumor, its low-grade counterpart usually demonstrates a more benign nature and several systems have, therefore, been proposed to grade this neoplasm.
This report analyzes 43 patients suffering from head and neck MEC, who were treated in our department during the period from 1989 to 2005. The relationship between clinical and pathologic characteristics and survival rate was investigated.
The 5-year overall and disease-free survival rate was 62.3 and 57.2%. Multivariate analysis demonstrated that the parameters that significantly affected survival were the patient’s age (P = 0.040) and treatment method (P = 0.011).
The patient’s age and treatment method is the prognostic parameter in this study. Although complete surgical resection is the standard treatment for MEC, we should aggressively consider adjunctive radiotherapy in those cases that have a high risk of recurrence and poor prognosis.
Magnetic resonance imaging mammography is performed to determine the extent of lesions and to detect occult lesions, but preoperative diagnosis by breast computed tomography (CT) is less common.
We performed a retrospective study of detection of mammographically occult multiple lesions using breast CT. The subjects were 407 female patients (median age: 56 years old; median tumor size: 1.9 cm) with breast cancer who underwent preoperative, contrast-enhanced breast CT.
CT detected 73 incidental-enhanced breast nodules (median size: 0.8 cm) in 73 patients that were undetectable by conventional methods. Age, size of the main lesion or laterality of lesions did not differ between patients with and without incidental nodules, but the frequency of mastectomy was significantly higher in those with incidental nodules. Of the 73 incidental nodules, 22 (30%) were in the same quadrant as the main lesion, 26 (36%) were in other quadrants and 25 (34%) were in the opposite breast. On qualitative diagnosis by CT, 48 were suspected to be malignant (66%), 17 benign (23%) and eight non-specific (11%). In histological evaluation of 44 of the 48 nodules suspected to be malignant, 24 were malignant (invasive carcinoma: 22, non-invasive carcinoma: 2); of seven of the 17 nodules suspected to be benign, all were benign; and of three of the eight non-specific nodules, one was non-invasive carcinoma. The discovery rate of clinically and mammographically occult multiple lesions by preoperative breast CT was 6%.
We conclude that breast CT is useful for the detection of occult lesions and choice of surgical procedure.
Esophageal small-cell cancer is a rare disease, and standard therapy has not yet been established.
A total of 12 esophageal small-cell carcinoma patients were treated with CPT-11 (70 mg/m2) on Days 1 and 15 and CPT-11 plus CDDP (80 mg/m2) on Day 1 with each cycle repeated every 4 weeks at our institution.
A total of 46 chemotherapy courses were given (median, 3.5). There were two complete responses and eight partial responses. The median survival time was 417 (97–1626) days, and three patients were still alive for >40 months. Grade 4 neutropenia was observed in two patients, Grade 4 anemia in one patient, Grade 3–4 diarrhea in three patients and Grade 3–4 hyponatremia in three patients. Other adverse reactions seen were mild with no treatment-related deaths observed.
To our knowledge, this is the first report of the series of more than 10 patients with small-cell carcinoma of the esophagus treated with the same chemotherapy regimen. The combination of CPT-11 and CDDP appears to be effective therapy of this disease with acceptable toxicity profile. We believe that this regimen is one of the options to be considered for treatment of esophageal small-cell carcinoma.
As prognosis of advanced gastric cancer is still poor, a standard regimen after first-line fluorouracil (FU)-based chemotherapy has not yet been established. Therefore, we conducted a phase II study to evaluate the efficacy and toxicity of sequential treatment with methotrexate (MTX) and also 5-FU as second-line chemotherapy in patients with advanced gastric cancer.
Treatment consisted of weekly doses of MTX (100 mg/m2, i.v. bolus), followed by 5-FU (600 mg/m2, i.v. bolus) 3 h after MTX administration. Leucovorin rescue therapy (six doses of 10 mg/m2, given at 6-h intervals) was commenced 24 h after a treatment with MTX. The primary endpoint was the response rate.
Between December 1992 and June 1995, 56 patients were registered in this study and one was ineligible. All registered patients were included in all analyses. The median age of the patients was 60 years (20–75 years). Most patients (75%) had a performance status of 0 or 1, and 51 (90%) received 5-FU-based chemotherapy as first-line treatment. The major adverse events were myelosuppression and gastrointestinal toxicity. Grade 4 neutropenia occurred in 6.3% of the patients. The overall objective response rate was 9.0% [five partial responses among 56 patients, 95% confidence interval (CI): 3.0–20%]. The median overall survival time was 237 days, and the 1-year survival proportion was 21.4%.
Sequential MTX/5-FU therapy provides good survival outcomes with tolerable toxicity despite a limited response in patients with previously treated advanced gastric cancer. This regimen is now being evaluated in a randomized study in patients with pretreated advanced gastric cancer, by the Japan Clinical Oncology Group.
Hepatocellular carcinoma with inferior vena cava invasion is a rare but fatal condition of disease progression. The aim of this study was to analyze the results of treatment for hepatocellular carcinoma with inferior vena cava invasion by three-dimensional conformal radiation therapy.
From 1990 to 2006, 18 histopathologically confirmed hepatocellular carcinoma patients with inferior vena cava invasion who were unsuitable for surgery were treated by three-dimensional conformal radiation therapy at our hospital with two to four static or dynamic conformal arc fields.
A median total tumor dose of 50 Gy (range 30–60 Gy) was delivered. The progression-free rate was 91.6% among the patients in whom follow-up computed tomography was obtained. Actuarial survival at 1 year was 33.3%, and the median survival period was 5.6 months.
Three-dimensional conformal radiation therapy might offer a chance of long survival for a part of the hepatocellular carcinoma patients with inferior vena cava invasion, since a third of such patients survived more than a year. Additional treatments should be considered to prevent distant metastases and hepatic functional deterioration after three-dimensional conformal radiation therapy.
To evaluate the efficacy of three additional cycles of chemotherapy in patients with the International Federation of Gynecology and Obstetrics Stage III or IV, who achieved a complete response after six cycles of intravenous adjuvant paclitaxel/carboplatin after surgery.
The clinical data of 94 patients with complete response after six cycles of adjuvant paclitaxel/carboplatin after surgery between January 1997 and March 2007 were reviewed retrospectively. Three additional cycles using the same chemotherapy were administered to 57 patients as consolidation chemotherapy (Group 1). Thirty-seven patients without the additional cycles served as controls (Group 2). Disease-free survival (DFS) and overall survival (OS) were evaluated using the Kaplan–Meier method with the log-rank test. The importance of consolidation chemotherapy as a prognostic factor affecting survival was examined using the Cox's proportional hazard analysis. The incidence of chemotherapy-induced hematological toxicities was compared between the two groups using chi-square test.
Median DFS and mean OS were not significantly different between the two groups (15 versus 22 months, P = 0.703; 69 versus 73 months, P = 0.891, respectively). Consolidation chemotherapy was not a prognostic factor of survival although optimal debulking surgery and lower value of serum CA-125 levels after six cycles of the chemotherapy were prognostic factors improving DFS (P < 0.01). Grade 3 or 4 leukopenia was more common in patients treated with consolidation chemotherapy than in those not treated (50.9 versus 21.6%, P = 0.004).
Consolidation chemotherapy using paclitaxel/carboplatin may be inefficient and relatively toxic to advanced-stage epithelial ovarian cancer patients with complete response to six cycles of the same chemotherapy after surgery.