Safety and tolerability of stereotactic radiotherapy combined with durvalumab with or without tremelimumab in advanced non-small cell lung cancer, the phase I SICI trial.

INTRODUCTION: This phase I study primarily addresses the safety and tolerability of Stereotactic radiotherapy on the primary tumor combined with double Immune Checkpoint Inhibition (SICI) in patients with non-small cell lung cancer (NSCLC). Increasing the release of neoantigens by radiotherapy might enhance response to immunotherapy. Especially, by targeting trunk mutations in the primary tumor. MATERIALS AND METHODS: In three sequential cohorts, immunotherapy regimes combined with stereotactic body radiotherapy (SBRT) on the primary tumor (1x20 Gy on 9 cc) were studied in stage IIIB/IV NSCLC patients progressing on chemotherapy. The first cohort (n = 3) received durvalumab. The second (n = 6) received a combination of tremelimumab and durvalumab followed by durvalumab monotherapy. The third cohort (n = 6) was similar except that the combination was reversed. Descriptive statistics were used to assess safety parameters and the exploratory outcomes of efficacy. Adverse events were reported using NCI CTCAE version 4.03. Exhaled breath was analyzed at baseline. RESULTS: Fifteen patients were included. Median irradiated volume was 9.13 cc, on a median primary tumor volume of 79 cc. There were seven patients with grade 1-2, and two patients with grade 3 treatment related adverse events. There was 1 dose limiting toxicity (colitis) with double immunotherapy. CONCLUSION: The combination of SBRT to the primary tumor and double immunotherapy in advanced NSCLC patients is safe and feasible.

Application of a mixed imaging sequence for MR imaging characterization of human breast disease.

Single slice MR images were obtained from 9 normal breasts, 17 breasts with benign tumors, and 11 breasts with malignant tumors using an interleaved (mixed) spin echo (SE) inversion-recovery (IR) imaging sequence. SE and IR MR images were synthesized with variable repetition, echo and inversion times from the mixed sequence data. These images were used to qualitatively evaluate the contrast possibilities available when imaging the breast with MR imaging. Proton T1 and T2 relaxation times were determined for normal breast tissues and malignant and benign breast tumors from pure T1 and T2 images calculated using the mixed sequence data. The mean T1 value in benign tumors of 1,049.02 +/- 40.31 was found to be significantly longer (p < 0.0001) than the mean value of malignant tumors (876.09 +/- 27.83) and normal tissues (795.64 +/- 21.12). The value of T2 in benign tumors (89.15 +/- 8.33) was significantly longer (p < 0.01) than the value of T2 in normal tissues (62.82 +/- 4.06). The mixed sequence can be applied to improve image contrast between malignant tumors, benign tumors, and normal tissues of the breast and can potentially differentiate between these tissues in vivo.

Magnetic resonance image appearance of hamartoma of the breast.

The magnetic resonance imaging (MRI) features of a breast hamartoma are presented. The hamartoma was evaluated using several imaging techniques with and without gadolinium-DTPA. This case demonstrates that, in selected cases, MRI is of value as an adjunct to mammography and sonography.

Breast disease evaluation with fat-suppressed magnetic resonance imaging.

Thirty patients with a variety of pathologically confirmed malignant and benign pathologic lesions of the breast were evaluated with a spectrally selective fat suppression imaging technique to obtain fat-suppressed images of the breast. The technique, a selective partial inversion-recovery (SPIR) method, demonstrated the architectural relationship of malignant and benign tumors with respect to the normal water-containing elements of the breast. These relationships included signs of advanced malignant disease such as tissue retraction, invasive growth, and multicentricity, which appeared on the fat-suppressed images. Fat-suppressed imaging provided useful information for assessing the breasts of both pre- and postmenopausal women, especially in the latter group, where fatty involution of the breast is common. Microcysts, which are normally not visualized by conventional methods, were demonstrated and associated with patients having confirmed fibrocystic disease of the breast. As expected, the SPIR technique did not improve the ability to distinguish between tissues having similar T1 and T2 relaxation time values, such as malignant tumors and normal breast parenchymal tissues. The technique was able to demonstrate that the intense lipid signal, known to be responsible for obscuring the borders of water-fat interfaces and small tumors, could be eliminated in a variety of pathological settings.

MRI appearance of multiple papilloma of the breast.

Magnetic resonance imaging (MRI) is capable of providing a different diagnostic perspective in the evaluation of breast lesions. Its application in a single patient with multiple papilloma of the breast is described. MRI convincingly demonstrated the multicentric nature of the disease and helped to select a proper treatment plan. This report makes it clear that MRI could serve as an adjunct to mammography and sonography in selected cases.

Blocking by anti-idiotypic antibodies of monoclonal antibody mediated protection in mice against encephalomyocarditis virus induced diabetes and lethal disease.

Monoclonal antibodies (MA) UM 21.1 and UM 21.2 protect mice against encephalomyocarditis virus (D-variant) induced diabetes and lethal disease. MA-mediated protection in vivo as well as neutralization in vitro could be specifically blocked by anti-idiotypic antibodies.

Yeast species utilizing uric acid, adenine, n-alkylamines or diamines as sole source of carbon and energy.

Yeast strains utilizing uric acid, adenine, monoamines or diamines as sole source of carbon and energy were isolated from several soil samples by the enrichment culture method. The most common species was Trichosporon cutaneum. Strains of Candida catenulata, C. famata, C. parapsilosis, C. rugosa, Cryptococcus laurentii, Stephanoascus ciferrii and Tr. adeninovorans were also isolated. All strains utilizing uric acid as sole carbon source utilized some primary n-alkyl-l-amines, hydroxyamines or diamines as well. The ascomycetous yeast strains showing these characteristics all belonged to species known to assimilate hydrocarbons. Type strains of hydrocarbon-positive yeast species which were not found in the enrichment cultures generally assimilated putrescine, some type strains also butylamine or pentylamine, but none assimilated uric acid. Methanol-positive species were not isolated. Type strains of methanol-positive and of hydrocarbon-negative species did not assimilate uric acid, butylamine or putrescine. Assimilation of putrescine as sole source of carbon and energy may be a valuable diagnostic criterion in yeast taxonomy.