Ciguatoxin, the agent responsible for ciguatera, a disease produced in humans from ingestion of certain fishes, has been isolated from specimens of the moray eel, Gymnothorax javanicus. The toxin is apparently a lipid containing quaternary nitrogen, hydroxyl, and carbonyl functions.

BACKGROUND: Although concurrent chemoradiotherapy (CCRT) has become the standard approach for unresectable locally advanced non-small cell lung cancer (LA-NSCLC), most patients are not candidates for this treatment because of comorbidities. We evaluated the safety and efficacy of carbon ion radiotherapy (CIRT) in LA-NSCLC patients. METHODS: Patients with stage IIA to IIIA (UICC 7th edition) LA-NSCLC were enrolled in a sequential phase I/II trial. For a phase I dose escalation study, the total prescribed dose was increased by 4 Gray equivalents (GyE) in 2 steps, from 68 to 72 GyE and then to 76 GyE, using 16 fractions over 4 weeks. After determining the recommended dose, the phase II trial was started in an expanded cohort. RESULTS: Of the 36 patients treated in phase I, 2 grade 3 adverse events (radiation pneumonitis and tracheoesophageal fistula) were observed in the 76 GyE group. Accordingly, for phase II, the next consecutive 26 patients were treated with 72 GyE, with no grade 3 to 5 toxicities resulting. A total of 62 eligible patients were recruited. The majority of patients (49 of 62) were N0 or N1 patients, and the rest (13 of 62) were singlestation N2 patients. The median follow-up period was 25.2 months. The 2-year local control rate (LCR) and overall survival (OS) for the entire cohort were 93.1% and 51.9%, respectively. In particular, patients with cT3-4N0 had an excellent prognosis; the 2-year OS and LCR were 69.3% and 100%, respectively. CONCLUSIONS: Short-course CIRT monotherapy shows promise as an effective nonsurgical treatment for inoperable LA-NSCLC. Cancer 2015;121:1321-7.

Stereotactic body radiation therapy (SBRT) has a local control rate of 95% at 2 years for non-small cell lung cancer (NSCLC) and should improve the prognosis of inoperable patients, elderly patients, and patients with significant comorbidities who have early-stage NSCLC. The safety of SBRT is being confirmed in international, multi-institutional Phase Ⅱ trials for peripheral lung cancer in both inoperable and operable patients, but reports so far have found that SBRT is a safe and effective treatment for early-stage NSCLC and early metastatic lung cancer. Radiation pneumonitis (RP) is one of the most common toxicities of SBRT. Although most post-treatment RP is Grade 1 or 2 and either asymptomatic or manageable, a few cases are severe, symptomatic, and there is a risk for mortality. The reported rates of symptomatic RP after SBRT range from 9% to 28%. Being able to predict the risk of RP after SBRT is extremely useful in treatment planning. A dose-effect relationship has been demonstrated, but suggested dose-volume factors like mean lung dose, lung V20, and/or lung V2.5 differed among the reports. We found that patients who present with an interstitial pneumonitis shadow on computed tomography scan and high levels of serum Krebs von den Lungen-6 and surfactant protein D have a high rate of severe radiation pneumonitis after SBRT. At our institution, lung cancer patients with these risk factors have not received SBRT since 2006, and our rate of severe RP after SBRT has decreased significantly since then.

Radiomics, which involves the extraction of large numbers of quantitative features from medical images, has attracted attention in cancer research. In radiomics analysis, tumor segmentation is a crucial step. In this study, we evaluated the potential application of radiomics for predicting the histology of early stage non-small cell lung cancer (NSCLC) by analyzing interobserver variability in tumor delineation. Forty patient datasets were included in this study, 21 involving adenocarcinomas and 19 involving squamous cell carcinomas. All patients underwent stereotactic body radiotherapy treatment. In total, 476 features were extracted from each dataset, representing treatment planning, computed tomography images, and gross tumor volume (GTV). The definition of GTV can significantly affect the histology prediction. Therefore, in the present study, the effect of interobserver tumor delineation variability on radiomic features was evaluated by preparing 4 volumes of interest (VOIs) for each patient, as follows: the original GTV (which was delineated at treatment planning); two GTVs delineated retrospectively by radiation oncologists; and a semi-automatic GTV contoured by a medical physicist. Radiomic features extracted from each VOI were then analyzed using a naïve Bayesian model. Area-under-the-curve (AUC) analysis showed that interobserver variability in delineation is a significant factor in radiomics performance. Nevertheless, with 8 selected features, AUC values averaged over the VOIs were high (0.725 ± 0.070). The present study indicated that radiomics has potential for predicting early stage NSCLC histology despite variability in delineation. The high prediction accuracy implies that noninvasive histology evaluation by radiomics is a promising clinical application.

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Amplification of the c-er bB-2 gene (located on 17q11.2-12) is accompanied by overexpression of its cell surface receptor product, p185 ERBB2 . In pulmonary carcinomas, however, there has been disagreement between the reported frequencies of gene amplification and overexpression. To clarify their relationship, the correlation between the cellular expression of p185 ERBB2 and the level of c-erb B-2 gene amplification was studied. A total of 195 pulmonary carcinomas (182 primary and 13 metastatic) were examined immunohistochemically using a polyclonal antibody, which recognizes the internal domain of the human c-erb B-2 protein, and positive tumors were further examined for the gene amplification by dual-color fluorescence in situ hybridization using probes for centromere 17 and 17q11.2-12. By immunohistochemistry, distinct membrane staining was found in an adenocarcinoma, a large cell carcinoma and a metastatic carcinoma from the breast, and cytoplasmic and/or faint membranous staining was observed in 23 nonsmall cell lung carcinomas. It was in the two primaries and the metastatic carcinoma that more than 8-fold amplification of c-erb B-2 was found by fluorescence in situ hybridization. Especially, in the two primary carcinomas, tumor cells had amplified genes with the signals forming one or two clusters, indicating that the amplified gene was present in homogeneously staining regions. Among the 23 tumors, three tumors showed low-level amplification (less than 3-fold), which was differentiated from polysomy 17 found in the other two. In the 30 nonsmall cell lung carcinomas selected at random from 151 with negative immunostaining, there were five trisomy 17, but no tumors with the gene amplification. This suggests that although c-erb B-2 amplification in pulmonary carcinoma is rare, it occurs in the form of a homogeneously staining region and is thought to control the overexpression of the protein in the cell membrane. New adjuvant therapy using a humanized antibody to the oncoprotein may be beneficial to patients with these tumors.

Conclusions-The extent of the abnormality of myocardial fatty acid metabolism in idiopathic dilated cardiomyopathy reflects the severity of haemodynamic deterioration and histopathological changes. Type B mismatching is one of the important prognostic indicators in idiopathic dilated cardiomyopathy. (Heart 1999;81:153-159)