Showing papers by "Keith A. Cengel published in 2016"
TL;DR: The combination of intrapleural Ad.IFN, celecoxib, and chemotherapy proved safe in patients with MPM and support proceeding with a multicenter randomized clinical trial of chemo-immunogene therapy versus standard chemotherapy alone.
Abstract: Purpose: “In situ vaccination” using immunogene therapy has the ability to induce polyclonal antitumor responses directed by the patient9s immune system. Experimental Design: Patients with unresectable malignant pleural mesothelioma (MPM) received two intrapleural doses of a replication-defective adenoviral vector containing the human IFNα2b gene (Ad.IFN) concomitant with a 14-day course of celecoxib followed by chemotherapy. Primary outcomes were safety, toxicity, and objective response rate; secondary outcomes included progression-free and overall survival. Biocorrelates on blood and tumor were measured. Results: Forty subjects were treated: 18 received first-line pemetrexed-based chemotherapy, 22 received second-line chemotherapy with pemetrexed (n = 7) or gemcitabine (n = 15). Treatment was generally well tolerated. The overall response rate was 25%, and the disease control rate was 88%. Median overall survival (MOS) for all patients with epithelial histology was 21 months versus 7 months for patients with nonepithelial histology. MOS in the first-line cohort was 12.5 months, whereas MOS for the second-line cohort was 21.5 months, with 32% of patients alive at 2 years. No biologic parameters were found to correlate with response, including numbers of activated blood T cells or NK cells, regulatory T cells in blood, peak levels of IFNα in blood or pleural fluid, induction of antitumor antibodies, nor an immune-gene signature in pretreatment biopsies. Conclusions: The combination of intrapleural Ad.IFN, celecoxib, and chemotherapy proved safe in patients with MPM. OS rate was significantly higher than historical controls in the second-line group. Results of this study support proceeding with a multicenter randomized clinical trial of chemo-immunogene therapy versus standard chemotherapy alone. Clin Cancer Res; 22(15); 3791–800. ©2016 AACR.
67 citations
TL;DR: A phase 1 trial for high-grade premalignant and early superficial lesions of the head and neck using photodynamic therapy (PDT) with Levulan (ALA) with well tolerated results suggest use of larger treatment fields.
29 citations
TL;DR: In response to Katz and Husain’s question about additional endpoints for future trials comparing surgery with SABR, work by us and others suggests that inclusion of the patient-reported endpoints of global health-related quality of life and indirect costs and immune response activation after both S ABR and surgery is very informative.
Abstract: www.thelancet.com/oncology Vol 17 February 2016 e43 1 Chang JY, Senan S, Paul MA, et al. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Oncol 2015; 16: 630–37. 2 Chang JY, Senan S, Smit EF, Roth JA. Surgery versus SABR for resectable non-small-cell lung cancer—authors’ reply. Lancet Oncol 2015; 16: e374–75. 3 Louie AV, Haasbeek CJ, Mokhles S, et al. Predicting overall survival after stereotactic ablative radiation therapy in early-stage lung cancer: development and external validation of the Amsterdam prognostic model. Int J Radiat Oncol Biol Phys 2015; 93: 82–90. 4 Jones DR. Do we know bad science when we see it? J Thorac Cardiovasc Surg 2015; 150: 472–73. 5 Senthi S, Lagerwaard FJ, Haasbeek CJ, Slotman BJ, Senan S. Patterns of disease recurrence after stereotactic ablative radiotherapy for early stage non-small-cell lung cancer: a retrospective analysis. Lancet Oncol 2012; 13: 802–09. 6 Veluswamy RR, Ezer N, Mhango G, et al. Limited resection versus lobectomy for older patients with early-stage lung cancer: impact of histology. J Clin Oncol 2015; 33: 3447–53. 7 Louie AV, van Werkhoven E, Chen H, et al. Patient reported outcomes following stereotactic ablative radiotherapy or surgery for stage IA non-small-cell lung cancer: results from the ROSEL multicenter randomized trial. Radiother Oncol 2015; 117: 44–48. 8 Bernstein MB, Krishnan S, Hodge JW, Chang JY. Immunotherapy and stereotactic ablative radiotherapy (I-SABR): can systemic plus local control lead to a cancer cure? Nat Rev Clin Onc (in press). 9 Aerts JG, De Goeje P, Schram M, et al. MINI18.03—immune activation in early stage non-small cell lung cancer (NSCLC) following stereotactic ablative radiotherapy (SABR) and surgery (ID 2123). 16th World Conference on Lung Cancer; Denver, CO, USA; Sept 6–9, 2015. nodal staging before SABR in stage IA disease is being investigated in a prospective study (NCT01786590) to establish if a greater proportion of patients with nodal disease can be identifi ed via endobronchial ultrasound transbronchial needle aspiration than via a strategy of nodal staging according to PET-CT fi ndings only. Katz and Husain comment on a potential role for treatment of microscopic peritumoral disease with SABR, which identifies an area that merits further research, particularly in view of a Medicaid analysis of SEER showing worse survival in subgroups of patients undergoing a sublobar resection. Authors of this propensity score analysis noted that of patients with squamous cell carcinoma, neither wedge resection nor segmentectomy achieved survivals equivalent to lobectomy, whereas for adenocarcinomas, only a wedge resection was associated with a survival disadvantage compared with lobectomy. Finally, in response to Katz and Husain’s question about additional endpoints for future trials comparing surgery with SABR, work by us and others suggests that inclusion of the patient-reported endpoints of global health-related quality of life and indirect costs and immune response activation after both SABR and surgery is very informative. These preliminary data have shown intriguing results and are hypothesis generating.
25 citations
TL;DR: Since its publication, PDT has been increasingly utilized in clinical practice for the treatment of both benign and malignant conditions, and many of their questions have yielded new technologies and areas of investigation, thus remaining highly relevant nearly 40 years after their initial asking.
Abstract: Despite descriptions of light-mediated therapy in ancient texts and the discovery of photodynamic therapy (PDT) in the early 1900s, the landmark article in 1978 in Cancer Research by Dougherty and his colleagues at the Roswell Park Cancer Institute remains rightly viewed as the starting point for clinical PDT in modern medicine. As a large clinical series that explored many of the factors now viewed as critical determinates of PDT dose, efficacy, and toxicity, that study showed remarkable foresight, yet it also served to raise as many questions as it answered. Since its publication, PDT has been increasingly utilized in clinical practice for the treatment of both benign and malignant conditions, and many of their questions have yielded new technologies and areas of investigation, thus remaining highly relevant nearly 40 years after their initial asking. Moreover, continuing advances in our ability to measure physical properties such as absorbed light dose, photosensitizer concentration, tissue oxygen concentration, and singlet oxygen production in real-time may allow for adaptive modification of light delivery during PDT on a fine scale to optimize treatment response. Finally, combining molecularly targeted drugs and novel photosensitizers has the potential to improve further the therapeutic index and extend the spectrum of clinical PDT far beyond what was imagined when that sentinel manuscript was written. Cancer Res; 76(9); 2497-9. ©2016 AACRSee related article by Dougherty et al., Cancer Res 1978;38:2628-35Visit the Cancer Research 75(th) Anniversary timeline.
23 citations
TL;DR: It is shown that by exchanging the native silica tip for a fluorinated tip, a better nonstick property led to an increased sensitizer output and how the fluorination of the device tip increases biofouling resistance and can contribute to a new pointsource PDT tool.
Abstract: We describe progress on a one-step photodynamic therapy (PDT) technique that is simple: device tip delivery of sensitizer, oxygen and light simultaneously. Control is essential for their delivery to target sites to generate singlet oxygen. One potential problem is the silica device tip may suffer from biomaterial fouling and the pace of sensitizer photorelease is slowed. Here, we have used biomaterial (e.g. proteins, cells, etc.) from SQ20B head and neck tumors and whole blood for an assessment of fouling of the silica tips by adsorption. It was shown that by exchanging the native silica tip for a fluorinated tip, a better nonstick property led to an increased sensitizer output by ~10%. The fluorinated tip gave a sigmoidal photorelease where singlet oxygen is stabilized to physical quenching, whereas the native silica tip with unprotected SiO-H groups gave a slower (pseudolinear) photorelease. A further benefit from fluorinated silica is that 15% less biomaterial adheres to its surface compared to native silica based on a bicinchoninic acid assay (BCA) and X-ray photoelectron spectroscopy (XPS) measurements. We discuss how the fluorination of the device tip increases biofouling resistance and can contribute to a new pointsource PDT tool.
8 citations
4 citations