Effect of a Device-Free Compressed Shell Fixation Method on Hepatic Respiratory Movement: Analysis for Respiratory Amplitude of the Liver and Internal Motions of a Fiducial Marker

Purpose

Suppression of respiratory movement of the liver would be desirable for high-precision radiation therapy for liver tumors. We aimed to investigate the effect of our original device-free compressed shell fixation method and breathing instruction on suppression of respiratory movement. The characteristics of liver motion based on the movement of a fiducial marker were also analyzed.

Preparation of two-drug composite microparticles to improve the dissolution of insoluble drug in water for use with a 4-fluid nozzle spray drier.

In this study, we used a novel 4-fluid nozzle spray drier to prepare composite microparticles of a water-insoluble drug, flurbiprofen (FP), and a water-soluble drug, sodium salicylate (SS), for the purpose of improving the water solubility of FP. An ethanol solution of FP and an aqueous SS solution were simultaneously introduced through different liquid passages in the 4-fluid nozzle spray drier and then spray-dried. Quantitative elemental analysis suggested that the FP/SS ratio in each composite microparticle was nearly the same as the formulation ratio. We also found that SS and FP exist in a low crystallinity state in the composite particles. Release of FP from dissolved composite microparticles was markedly improved because of an increase in the effective surface area following rapid dissolution of SS. This study shows that it is possible to prepare FP-SS composite microparticles using a 4-fluid nozzle spray drier in single process and that this can improve the ability of FP to dissolve in water.     

A "supralethal dose phenomenon" revealed by cancer of the maxillary sinus

In this paper a so-called "supralethal dose phenomenon" is reported. Two groups of patients, all of whom were carrying proved squamous cell carcinoma of the same clinical stage in their maxillary sinuses, were compared after radiotherapy in our department. The radiotherapies applied to the two groups were very similar in terms of fraction number, treatment period, dose distribution and immobilization technique, but differed in dose, i.e., 5,500 cGy for one group of 9 patients and 5,750 cGy for the other group of 20 patients. The five-year survival rates of the two groups were 8/9 and 10/20, respectively, and the difference was statistically significant (p less than 0.05). All patients were observed for at least five years. Except for tumor stage, the status of the patients in the two groups, including primary site of the tumor in the sinus, patients' age and cause of death for the failed cases, are also discussed in detail.     

A Study on the Prognostic Evaluation of Carbon Ion Radiotherapy for Head and Neck Adenocarcinoma with C-11 Methionine PET

Purpose  

Carbon ion radiotherapy (CIRT) has been developed, and a phase I/II CIRT trial has been conducted in patients with adenocarcinoma in the head and neck region. We evaluated whether the l-methyl [11C]-methionine (MET) uptake could be an early predictor for local recurrence, metastasis, and the prognosis in patients with adenocarcinoma in the head and neck region.     

Carbon ion radiation therapy for prostate cancer: results of a prospective phase II study.

BACKGROUND AND PURPOSE: To determine the efficacy and feasibility of carbon ion radiotherapy (C-ion RT) for prostate cancer. PATIENTS AND METHODS: Between April 2000 and November 2003, 175 patients received C-ion RT using a recommended dose fractionation (66.0 GyE/20 fractions) established from prior studies. C-ion RT alone was performed for 33 patients constituting a low-risk group (Stage < or =T2a and PSA <20 ng/ml and Gleason score < or =6); the remaining 142 high-risk patients received an additional androgen deprivation therapy (ADT). RESULTS: The 4-year overall survival and bNED rates were 91% and 87%, respectively. Local control was achieved in all but one patient. The 4-year bNED rates were 87% in the low-risk group and 88% in the high-risk group. In very advanced diseases (Stage > or= T3a or PSA > or= 20 ng/ml or Gleason score > or =8), there was significant difference in the bNED rate according to period of ADT administration (ADT > or =24 months: 93%, ADT <24 months: 73%, p<0.01). Grade 2 late toxicities developed in 4 patients (2%) for the rectum and 9 patients (5%) for the genitourinary system but no Grade 3 or higher toxicity was observed. CONCLUSIONS: The effectiveness of C-ion RT for prostate cancer has been well confirmed. Based on these results, new study of a C-ion RT modified for the administration strategy of ADT according to the patient risk has been started by dividing patients into 3 groups, high-risk, intermediate-risk, and low-risk.     

Allelic loss on chromosomes 2q, 3p and 21q: possibly a poor prognostic factor in oral squamous cell carcinoma

Loss of heterozygosity (LOH) correlates with inactivate tumor suppressor gene. The aim of this study was to see if LOH on chromosomes 2q, 3p and 21q correlated with a poor prognostic factor in oral squamous cell carcinoma (SCC). We analyzed chromosomes 2q, 3p and 21q for LOH in 40 primary oral SCCs using 30 markers and constructed a deletion map for these chromosome arms. Significant LOH (>20%) occurred at alleles in chromosome bands 2q14–21 (21.7%), 2q32–35 (31.6%), 2q35 (21.1%), 2q36 (36.7%), 3p25 (32.4%), 3p21.3 (23.8%), 21q11.1 (52.4%), 21q21 (21.6%) and 21q22.1 (22.2%). A significant correlation was observed between the number of regions showing LOH at 2q and TNM clinical stage (P=0.0063), consistent with the progressive accumulation of genetic errors during the development oral SCC. The number at more than two LOH loci was significant with a poor prognosis at 2q (P=0.0208). These findings demonstrate that oral SCC exhibits genetic alterations at multiple loci and that allelic loss at more than two locations is indicative of a poor prognosis. This is the first study to demonstrate the prognostic significance of LOH at 2q, 3p and 21q for oral cancer and may help to identify patient who should receive more aggressive treatment.     

Primary sebaceous carcinoma of the lacrimal gland treated by carbon ion radiotherapy

Sebaceous carcinoma is a rare primary neoplasm of the lacrimal gland and, to the best of our knowledge, only six cases have been reported previously. Sebaceous carcinoma of the orbit more commonly occurs as secondary invasion from the eyelid, but may occur by way of metastatic spread from elsewhere in the body. We describe a patient who presented with a rapidly growing neoplasm of the lacrimal gland which, histologically, was a sebaceous carcinoma. The eyelid was entirely normal on examination. In this patient we found a single tumor cell line within the normal lacrimal gland. In this article we describe the diagnosis and treatment with carbon ion radiotherapy of primary sebaceous carcinoma of the lacrimal gland, a condition not previously reported in Japan.     

Rationale for carbon ion therapy in high-grade glioma based on a review and a meta-analysis of neutron beam trials

PurposeThe standard treatment of high-grade glioma is still unsatisfactory: the 2-year survival after radiotherapy being only 10–25%. A high linear energy transfer (LET) ionising radiotherapy has been used to overcome tumour radioresistance. An overview of the field is needed to justify future prospective controlled studies on carbon ion therapy.Materials and methodsA meta-analysis of clinical trials on neutron beam therapy and a literature review of clinical investigations on light ion use in high-grade glioma were carried out.ResultsFour randomised controlled trials on neutron beam therapy were retained. The meta-analysis showed a non-significant 6% increase of two-year mortality (Relative risk [RR] = 1.06 [0.97–1.15]) in comparison with photon therapy. Two phase I/II trials on carbon and neon ion therapy reported for glioblastoma 10% and 31% two-year overall survivals and 13.9 and 19.0 months median survivals, respectively.ConclusionThis meta-analysis suggests that neutron beam therapy does not improve the survival of high-grade glioma patients while there is no definitive conclusion yet regarding carbon therapy. The ballistic accuracy and the improved biological efficacy of carbon ions renew the interest in prospective clinical trials on particle beam radiotherapy of glioma and let us expect favourable effects of dose escalation on patients’ survival.     

Mutation of the p16/CDKN2 gene and loss of heterozygosity in malignant mucosal melanoma and adenoid cystic carcinoma of the head and neck

The purpose of this study was to investigate the molecular biological characteristics of malignant mucosal melanoma (MMM) and adenoid cystic carcinoma (ACC) of the head and neck. We analyzed the common genetic abnormalities that may help to identify the loci in the genes involved in the development of MMM and ACC of the head and neck by PCR-LOH on chromosomes 1p, 6q, 9p, 10q, 11q, 12q, 17p, and 19q. LOH was observed in 6 of 12 cases of MMM and in 12 of 15 cases of ACC informative for at least one of the loci analyzed. One distinct deleted region was identified at chromosome 9p21. In addition, to identify a possible involvement of p16/CDKN2 PCR-SSCP and auto-DNA sequence analysis were also performed to detect any mutation of the p16/CDKN2. Particularly, 2 missense mutations were detected in codon 225 and 226, both in MMM and ACC. There were mutational hot spots in the p16/CDKN2 gene. These results suggested that mutation of the p16/CDKN2 gene was a common factor in the development of human MMMs and ACCs, while this gene may be correlated with development and/or progression of a subtype and play a role in the oncogenesis of these cancers.