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12. Accelerated Hypofractionated Chemoradiation Followed by Stereotactic Ablative Radiotherapy Boost for Locally Advanced, Unresectable Non-Small Cell Lung Cancer: Final Results from a Nonrandomized Controlled Clinical Trial.

Author

Lee, P., Goldman, J., Garon, E., Luterstein, E., Neilsen, B.K., Lee, J.M., Felix, C., Cao, M., Tenn, S.E., Low, D., Kupelian, P.A., Steinberg, M.L., and Wu, T.C.

Subjects
*STEREOTACTIC radiotherapy, *NON-small-cell lung carcinoma, *IMMUNE checkpoint inhibitors, *CARDIOTOXICITY, *OVERALL survival, *RADIOTHERAPY
Abstract

Intrathoracic progression remains the predominant pattern of failure in patients treated with concurrent chemoradiation followed by a consolidation immune checkpoint inhibitor for locally advanced, unresectable non-small cell lung cancer (NSCLC). The objective of this study was to determine the maximum tolerated dose (MTD) and use of hypofractionated concurrent chemoradiation with an adaptive stereotactic ablative radiotherapy (SABR) boost. This was an early-phase, single institution, radiation dose-escalation nonrandomized controlled trial with concurrent chemotherapy among patients with clinical stage II or III NSCLC who were inoperable or refused surgery. Patients were enrolled and treated from May 2011 to May 2018 with a median patient follow-up of 18.2 months. Patients advanced to a higher SABR boost dose if dose-limiting toxicity (any grade 3 or higher pulmonary, GI, or cardiac toxicities, or any non-hematologic grade 4 or higher toxicities) occurred in fewer than 33% of the boost cohort within 90 days of follow-up. The current analyses were conducted from January to September 2023. All patients first received 4 Gy x 10 fractions followed by an adaptive SABR boost to residual metabolically active disease, consisting of an additional 25 Gy (low, 5 Gy x 5 fractions), 30 Gy (intermediate, 6 Gy x 5 fractions), or 35 Gy (high, 7 Gy x 5 fractions) with concurrent weekly carboplatin/paclitaxel. Data from 28 patients (median age, 70 [51-88] years; 16 [57%] male; 24 [86%] with stage III disease) enrolled across the low - (n = 10), intermediate- (n = 9), and high- (n = 9) dose cohorts were evaluated. The protocol specified MTD was not exceeded. The incidence of non-hematologic acute and late (>90 days) grade 3 or higher toxicities were 11% and 7%, respectively. No grade 3 toxicities were observed in the intermediate-dose boost cohort. Two deaths occurred in the high-dose cohort. Two-year local control was 74.1%, 85.7%, and 100.0% for the low-, intermediate-, and high-dose cohorts, respectively. Two-year overall survival was 30.0%, 76.2%, 85.7%, and 100.0% for the low-, intermediate-, and high-dose cohorts, respectively. This early-phase dose-escalation nonrandomized controlled trial showed that concurrent chemoradiation with an adaptive SABR boost to 70 Gy in 15 fractions with concurrent chemotherapy is safe and effective regimen for patients with locally advanced, unresectable NSCLC. This regimen may warrant further exploration and integration with immunotherapy in patients with unresectable stage II-III NSCLC in the CRT-IO era. [ABSTRACT FROM AUTHOR]

Published
2024
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19. Ponatinib in Refractory Ph-Positive Leukemias: A Phase 2 Trial

Author

Cortes, J E, Kim, D-W, Pinilla-Ibarz, J, le Coutre, P, Paquette, R, Chuah, C, Nicolini, F E, Apperley, J, Khoury, H J, Talpaz, M, DiPersio, J, DeAngelo, D J, Abruzzese, E, Rea, D, Baccarani, M, Müller, M C, Gambacorti-Passerini, C, Wong, S, Lustgarten, S, Rivera, V M, Clackson, T, Turner, C D, Haluska, F G, Guilhot, F, Deininger, M W, Hochhaus, A, Hughes, T, Goldman, J, Shah, N P, and Kantarjian, H

Published
2013

36. Experimental investigation of geologically produced antineutrinos with KamLAND

Author

Araki, T., Enomoto, S., Furuno, K., Gando, Y., Ichimura, K., Ikeda, H., Inoue, K., Kishimoto, Y., Koga, M., Koseki, Y., Maeda, T., Mitsui, T., Motoki, M., Nakajima, K., Ogawa, H., Ogawa, M., Owada, K., Ricol, J.-S., Shimizu, I., Shirai, J., Suekane, F., Suzuki, A., Tada, K., Takeuchi, S., Tamae, K., Tsuda, Y., Watanabe, H., Busenitz, J., Classen, T., Djurcic, Z., Keefer, G., Leonard, D., Piepke, A., Yakushev, E., Berger, B. E., Chan, Y. D., Decowski, M. P., Dwyer, D. A., Freedman, S. J., Fujikawa, B. K., Goldman, J., Gray, F., Heeger, K. M., Hsu, L., Lesko, K. T., Luk, K.-B., Murayama, H., O'Donnell, T., Poon, A. W. P., Steiner, H. M., Winslow, L. A., Mauger, C., McKeown, R. D., Vogel, P., Lane, C. E., Miletic, T., Guillian, G., Learned, J. G., Maricic, J., Matsuno, S., Pakvasa, S., Horton-Smith, G. A., Dazeley, S., Hatakeyama, S., Rojas, A., Svoboda, R., Dieterle, B. D., Detwiler, J., Gratta, G., Ishii, K., Tolich, N., Uchida, Y., Batygov, M., Bugg, W., Efremenko, Y., Kamyshkov, Y., Kozlov, A., Nakamura, Y., Karwowski, H. J., Markoff, D. M., Nakamura, K., Rohm, R. M., Tornow, W., Wendell, R., Chen, M.-J., Wang, Y.-F., and Piquemal, F.

Published
2005
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44. A Phase 2 Trial of Ponatinib in Philadelphia Chromosome–Positive Leukemias

Author

Cortes, J. E., Kim, D.-W., Pinilla-Ibarz, J., le Coutre, P., Paquette, R., Chuah, C., Nicolini, F. E., Apperley, J. F., Khoury, H. J., Talpaz, M., DiPersio, J., DeAngelo, D. J., Abruzzese, E., Rea, D., Baccarani, M., Müller, M. C., Gambacorti-Passerini, C., Wong, S., Lustgarten, S., Rivera, V. M., Clackson, T., Turner, C. D., Haluska, F. G., Guilhot, F., Deininger, M. W., Hochhaus, A., Hughes, T., Goldman, J. M., Shah, N. P., and Kantarjian, H.

Published
2013
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48. Bone marrow derivation of pericryptal myofibroblasts in the mouse and human small intestine and colon. (Rapid Communication)

Author

Brittan, M., Hunt, T., Jeffery, R., Poulsom, R., Forbes, S.J., Hodivala-Dilke, K., Goldman, J., Alison, M.R., and Wright, N.A.

Subjects
Bone marrow -- Transplantation, Gastrointestinal diseases -- Care and treatment, Health, Care and treatment
Abstract

Background and aims: In order to establish whether extraintestinal cells contribute to the turnover and repair of gastrointestinal tissues, we studied the colons and small intestines of female mice that [...]

Published
2002

49. Control of the shape of a thrombus-neointima-like structure by blood shear stress

Author

Liu, S.Q., Zhong, L., and Goldman, J.

Subjects
Engineering and manufacturing industries, Science and technology
Abstract

Fluid mechanical factors are thought to influence vascular morphogenesis. Here we show how blood shear stress regulates the shape of a thrombus-neointima-like tissue on a polymer micro-cylinder implanted in the center of the rat vena cava with the microcylinder perpendicular to blood flow. In this model, the micro-cylinder is exposed to a laminar flow with a known shear stress field in the leading region and a vortex flow in the trailing region. At 1, 5, 10, 20, and 30 days after implantation, it was found that the micro-cylinder was encapsulated by a thrombus-neointima-like tissue with a streamlined body profile. The highest growth rate of the thrombus-neointima-like tissue was found along the trailing and leading stagnation edges of the micro-cylinder. Blood shear stress in the laminar flow region was inversely correlated with the rate of thrombus formation and cell proliferation, and the percentage of smooth muscle [alpha] actin-positive cells. These biological changes were also found in the trailing vortex flow region, which was associated with lowered shear stress. These results suggest that blood shear stress regulates the rate of thrombus and neointimal formation and, thus, influences the shape of the thrombus-neointima-like structure in the present model. [DOI: 10.1115/1.1428744] Keywords: Vortex Blood Flow, SMC Proliferation, Neointimal Morphogenesis

Published
2002

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