Data support chemotherapy combined with antiangiogenic therapy in metastatic urothelial cancer (m... more Data support chemotherapy combined with antiangiogenic therapy in metastatic urothelial cancer (mUC) and muscle-invasive bladder cancer (MIBC). We investigated the efficacy and safety of gemcitabine, cisplatin, and sunitinib (GCS) in mUC and MIBC in parallel phase II trials. Trial 1 enrolled 36 patients with mUC who were chemotherapy naive; trial 2 enrolled 9 patients with MIBC. The primary endpoints for trials 1 and 2 were response rate and pathologic complete response, respectively. GCS was given as first-line treatment for patients with mUC and as neoadjuvant therapy for patients with MIBC. The Simon minimax 2-stage design was used for an objective response rate in trial 1 and for the pathologic complete response rate in trial 2. The initial trial 1 GCS dose was gemcitabine 1000 mg/m(2) intravenously, days 1 and 8; cisplatin 70 mg/m(2) intravenously, day 1; and sunitinib 37.5 mg orally daily, days 1 to 14 of a 21-day cycle. These doses proved intolerable. The doses of gemcitabine and cisplatin were subsequently reduced to 800 and 60 mg/m(2), respectively, without an improvement in drug delivery, and the trial was closed. This lower-dose regimen was applied in trial 2, which was stopped early due to excess toxicity. Grade 3 to 4 hematologic toxicities occurred in 70% (23/33) of patients in trial 1 and 22% (2/9) of patients in trial 2. In trial 1, the response rate was 49% (95% CI, 31%-67%); in trial 2, the pathologic complete response was 22% (2/9). Due to early closure secondary to toxicity, the sample sizes of both trials were small. Delivery of GCS was hampered by excessive toxicity in both advanced and neoadjuvant settings.
Objectives. To present our preliminary clinical results of transrectal high-intensity focused ult... more Objectives. To present our preliminary clinical results of transrectal high-intensity focused ultrasound (HIFU) in Stage T1b-2N0M0 prostate cancer. Efforts are being made to provide minimally invasive alternative treatment options with equal efficacy and fewer side effects. HIFU delivers ultrasound energy with rapid thermal necrosis of tissue in the focal region without damaging the surrounding tissue.Methods. We performed 28 HIFU treatments
A novel method for the production of adenoviral vectors on a scale sufficient to support most res... more A novel method for the production of adenoviral vectors on a scale sufficient to support most research applications and early phase clinical trials is presented. This method utilizes serum-free cell culture medium and a hollow fiber cell culture apparatus. Significantly less time and space are required than in conventional methods, and the resulting adenovirus is collected in a much smaller volume, simplifying the purification steps. The protocol described is a reproducible, convenient, biologically safe, and environmentally sound method for the production of adenoviral vectors for laboratory use and has the potential to scale-up the adenovirus production for clinical use.
To evaluate trends in utilization of robotic-assistance in partial nephrectomy and assess the ass... more To evaluate trends in utilization of robotic-assistance in partial nephrectomy and assess the association between cost and utilization. Using the 2009 to 2012 Nationwide Inpatient Sample database, we identified all adult (>17 years) patients undergoing partial nephrectomy for localized primary renal malignancy. Coding for robotic-assistance (17.4x) began in the final quarter of 2008. The primary outcome was total hospital cost exclusive of physician fees. A multiple linear regression model was used to adjust for patient and hospital characteristics. Between 2009 and 2012, there were 32,664 (58%) open, 3,498 (6%) laparoscopic, and 20,350 (36%) robot-assisted partial nephrectomies performed in the United States. Between 2009 and 2012, the total number of partial nephrectomies semiannually increased by 93% (5,114 to 9,845) with robotic partial nephrectomies (RPN) representing more than 80% of the increase. RPN increased from 1,029 cases in the first half of 2009 to 4,840 in the last...
190 Background: The optimal sequence and combination of life-extending anticancer therapies in mC... more 190 Background: The optimal sequence and combination of life-extending anticancer therapies in mCRPC pts remains unknown. Sipuleucel-T (sip-T), an autologous cellular immunotherapy approved for the therapy of asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC) pts, was evaluated in combination with abiraterone acetate and prednisone (abi) in the phase II STAMP trial (NCT01487863), with pts randomly assigned to receive CON sip-T + abi or SEQ sip-T followed by abi. The combination was well-tolerated and did not alter the immune response parameters that correlate with overall survival (OS) (Small Clin Can Res 2015). Here, we present long-term follow-up of clinical outcomes, including OS. Methods: mCRPC pts were randomized 1:1 to CON or SEQ therapy with sip-T and abi. Abi began 1 day after (CON) or at wk 10 (SEQ) after the first sip-T infusion and continued for 26 wk of therapy, after which continued abi therapy was permitted. Long-term clinical...
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2006
Articular cartilage is comprised of three histologic zones that exhibit different Young's mod... more Articular cartilage is comprised of three histologic zones that exhibit different Young's moduli. In addition, with age and disease the moduli can be altered. Therefore,diagnosis of joint diseases can be accomplished by detecting biomechanical properties of articular cartilage. In this report we investigate the feasibility of ultrasound elastography of bovine articular cartilage (n=5) employing instantaneous static compression using high-resolution (55MHz) ultrasound elastography in vitro as a potential arthroscopic technique. Elastograms were computed using cross-correlation technique and a gradient operator. The elastograms revealed near-zero strains within the samples, except at the articular surface and the interface between zones 1 and 2. The boundary conditions associated with the loading technique implemented herein that have to allow for a large acoustic window during imaging represent a fundamental challenge toward imparting local strains to the articular cartilage. Des...
Osteocalcin (OC), a noncollagenous bone matrix protein, is expressed in high levels by osteoblast... more Osteocalcin (OC), a noncollagenous bone matrix protein, is expressed in high levels by osteoblasts. To determine whether the OC promoter mediates cell-specific gene expression in cells of osteoblast lineage, we constructed a recombinant adenovirus, Ad-OC-TK, which contains the OC promoter that drives the expression of herpes simplex virus thymidine kinase (TK). We tested the expression of TK by this virus in osteoblast cell lines as well as in non-osteoblastic cell lines by assessing the enzyme activity of TK in vitro. Whereas the OC promoter failed to drive the expression of the TK gene in several non-osteoblastic cell lines such as WH, a human bladder transitional carcinoma, and NIH 3T3, an embryonic mouse fibroblast cell line, the OC promoter mediated high levels of expression in osteoblast cell lines including murine ROS and human MG-63 cells. The addition of acyclovir (ACV), a pro-drug for the inhibition of cell proliferation, resulted in the induction of osteoblast-specific ce...
Clinical cancer research : an official journal of the American Association for Cancer Research, Jan 15, 2003
Childhood osteogenic sarcoma (OS) is a rare bone cancer occurring primarily in adolescents. The N... more Childhood osteogenic sarcoma (OS) is a rare bone cancer occurring primarily in adolescents. The North American pediatric cooperative groups have performed a series of clinical treatment trials in this disease over the past several decades, and biology studies of tumor tissue have been an important study component. A meeting was held in Bethesda, Maryland on November 29-30, 2001, sponsored by the NIH Office of Rare Diseases, the Children's Oncology Group, and the National Cancer Institute-Cancer Therapy Evaluation Program with the general objectives: (a) to review the current state of knowledge regarding OS biology; (b) to identify, prioritize, and support the development of biology studies of potential clinical relevance in OS; and (c) to discuss the available tissue resources and the appropriate methods for analysis of OS samples for the conduct of biology studies. This report summarizes the information presented and discussed by the meeting participants.
The Journal of the Acoustical Society of America, 2001
The SonablateTM system for transrectal image-guided high intensity focused ultrasound (TR-HIFU) t... more The SonablateTM system for transrectal image-guided high intensity focused ultrasound (TR-HIFU) treatment of prostate diseases has been in clinical use since 1992. Recently, we developed the third generation of the system, call SonablateTM 500, with major improvements aimed specifically toward localized prostate cancer treatment. Salient features of the SonablateTM 500 include: (1) PC-based digital technology, (2) multifocal lengths probe with split beam transducer to cover a wide range of tissue depths (2.5–4.5 cm), (3) an upgraded treatment planning and control software with safety features such as reflectivity index measurement (RIMTM) and transducer tissue measurement (TTMTM); and (4) 3-D volume image rendering of the prostate. The SonablateTM 500 platform was tested in an in vivo canine experimental study in which the entire prostate was ablated. The prostate ultrasound images before and post HIFU treatment show very good correlation to the planned lesion. Histology delineated ...
Data support chemotherapy combined with antiangiogenic therapy in metastatic urothelial cancer (m... more Data support chemotherapy combined with antiangiogenic therapy in metastatic urothelial cancer (mUC) and muscle-invasive bladder cancer (MIBC). We investigated the efficacy and safety of gemcitabine, cisplatin, and sunitinib (GCS) in mUC and MIBC in parallel phase II trials. Trial 1 enrolled 36 patients with mUC who were chemotherapy naive; trial 2 enrolled 9 patients with MIBC. The primary endpoints for trials 1 and 2 were response rate and pathologic complete response, respectively. GCS was given as first-line treatment for patients with mUC and as neoadjuvant therapy for patients with MIBC. The Simon minimax 2-stage design was used for an objective response rate in trial 1 and for the pathologic complete response rate in trial 2. The initial trial 1 GCS dose was gemcitabine 1000 mg/m(2) intravenously, days 1 and 8; cisplatin 70 mg/m(2) intravenously, day 1; and sunitinib 37.5 mg orally daily, days 1 to 14 of a 21-day cycle. These doses proved intolerable. The doses of gemcitabine and cisplatin were subsequently reduced to 800 and 60 mg/m(2), respectively, without an improvement in drug delivery, and the trial was closed. This lower-dose regimen was applied in trial 2, which was stopped early due to excess toxicity. Grade 3 to 4 hematologic toxicities occurred in 70% (23/33) of patients in trial 1 and 22% (2/9) of patients in trial 2. In trial 1, the response rate was 49% (95% CI, 31%-67%); in trial 2, the pathologic complete response was 22% (2/9). Due to early closure secondary to toxicity, the sample sizes of both trials were small. Delivery of GCS was hampered by excessive toxicity in both advanced and neoadjuvant settings.
Objectives. To present our preliminary clinical results of transrectal high-intensity focused ult... more Objectives. To present our preliminary clinical results of transrectal high-intensity focused ultrasound (HIFU) in Stage T1b-2N0M0 prostate cancer. Efforts are being made to provide minimally invasive alternative treatment options with equal efficacy and fewer side effects. HIFU delivers ultrasound energy with rapid thermal necrosis of tissue in the focal region without damaging the surrounding tissue.Methods. We performed 28 HIFU treatments
A novel method for the production of adenoviral vectors on a scale sufficient to support most res... more A novel method for the production of adenoviral vectors on a scale sufficient to support most research applications and early phase clinical trials is presented. This method utilizes serum-free cell culture medium and a hollow fiber cell culture apparatus. Significantly less time and space are required than in conventional methods, and the resulting adenovirus is collected in a much smaller volume, simplifying the purification steps. The protocol described is a reproducible, convenient, biologically safe, and environmentally sound method for the production of adenoviral vectors for laboratory use and has the potential to scale-up the adenovirus production for clinical use.
To evaluate trends in utilization of robotic-assistance in partial nephrectomy and assess the ass... more To evaluate trends in utilization of robotic-assistance in partial nephrectomy and assess the association between cost and utilization. Using the 2009 to 2012 Nationwide Inpatient Sample database, we identified all adult (>17 years) patients undergoing partial nephrectomy for localized primary renal malignancy. Coding for robotic-assistance (17.4x) began in the final quarter of 2008. The primary outcome was total hospital cost exclusive of physician fees. A multiple linear regression model was used to adjust for patient and hospital characteristics. Between 2009 and 2012, there were 32,664 (58%) open, 3,498 (6%) laparoscopic, and 20,350 (36%) robot-assisted partial nephrectomies performed in the United States. Between 2009 and 2012, the total number of partial nephrectomies semiannually increased by 93% (5,114 to 9,845) with robotic partial nephrectomies (RPN) representing more than 80% of the increase. RPN increased from 1,029 cases in the first half of 2009 to 4,840 in the last...
190 Background: The optimal sequence and combination of life-extending anticancer therapies in mC... more 190 Background: The optimal sequence and combination of life-extending anticancer therapies in mCRPC pts remains unknown. Sipuleucel-T (sip-T), an autologous cellular immunotherapy approved for the therapy of asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC) pts, was evaluated in combination with abiraterone acetate and prednisone (abi) in the phase II STAMP trial (NCT01487863), with pts randomly assigned to receive CON sip-T + abi or SEQ sip-T followed by abi. The combination was well-tolerated and did not alter the immune response parameters that correlate with overall survival (OS) (Small Clin Can Res 2015). Here, we present long-term follow-up of clinical outcomes, including OS. Methods: mCRPC pts were randomized 1:1 to CON or SEQ therapy with sip-T and abi. Abi began 1 day after (CON) or at wk 10 (SEQ) after the first sip-T infusion and continued for 26 wk of therapy, after which continued abi therapy was permitted. Long-term clinical...
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2006
Articular cartilage is comprised of three histologic zones that exhibit different Young's mod... more Articular cartilage is comprised of three histologic zones that exhibit different Young's moduli. In addition, with age and disease the moduli can be altered. Therefore,diagnosis of joint diseases can be accomplished by detecting biomechanical properties of articular cartilage. In this report we investigate the feasibility of ultrasound elastography of bovine articular cartilage (n=5) employing instantaneous static compression using high-resolution (55MHz) ultrasound elastography in vitro as a potential arthroscopic technique. Elastograms were computed using cross-correlation technique and a gradient operator. The elastograms revealed near-zero strains within the samples, except at the articular surface and the interface between zones 1 and 2. The boundary conditions associated with the loading technique implemented herein that have to allow for a large acoustic window during imaging represent a fundamental challenge toward imparting local strains to the articular cartilage. Des...
Osteocalcin (OC), a noncollagenous bone matrix protein, is expressed in high levels by osteoblast... more Osteocalcin (OC), a noncollagenous bone matrix protein, is expressed in high levels by osteoblasts. To determine whether the OC promoter mediates cell-specific gene expression in cells of osteoblast lineage, we constructed a recombinant adenovirus, Ad-OC-TK, which contains the OC promoter that drives the expression of herpes simplex virus thymidine kinase (TK). We tested the expression of TK by this virus in osteoblast cell lines as well as in non-osteoblastic cell lines by assessing the enzyme activity of TK in vitro. Whereas the OC promoter failed to drive the expression of the TK gene in several non-osteoblastic cell lines such as WH, a human bladder transitional carcinoma, and NIH 3T3, an embryonic mouse fibroblast cell line, the OC promoter mediated high levels of expression in osteoblast cell lines including murine ROS and human MG-63 cells. The addition of acyclovir (ACV), a pro-drug for the inhibition of cell proliferation, resulted in the induction of osteoblast-specific ce...
Clinical cancer research : an official journal of the American Association for Cancer Research, Jan 15, 2003
Childhood osteogenic sarcoma (OS) is a rare bone cancer occurring primarily in adolescents. The N... more Childhood osteogenic sarcoma (OS) is a rare bone cancer occurring primarily in adolescents. The North American pediatric cooperative groups have performed a series of clinical treatment trials in this disease over the past several decades, and biology studies of tumor tissue have been an important study component. A meeting was held in Bethesda, Maryland on November 29-30, 2001, sponsored by the NIH Office of Rare Diseases, the Children's Oncology Group, and the National Cancer Institute-Cancer Therapy Evaluation Program with the general objectives: (a) to review the current state of knowledge regarding OS biology; (b) to identify, prioritize, and support the development of biology studies of potential clinical relevance in OS; and (c) to discuss the available tissue resources and the appropriate methods for analysis of OS samples for the conduct of biology studies. This report summarizes the information presented and discussed by the meeting participants.
The Journal of the Acoustical Society of America, 2001
The SonablateTM system for transrectal image-guided high intensity focused ultrasound (TR-HIFU) t... more The SonablateTM system for transrectal image-guided high intensity focused ultrasound (TR-HIFU) treatment of prostate diseases has been in clinical use since 1992. Recently, we developed the third generation of the system, call SonablateTM 500, with major improvements aimed specifically toward localized prostate cancer treatment. Salient features of the SonablateTM 500 include: (1) PC-based digital technology, (2) multifocal lengths probe with split beam transducer to cover a wide range of tissue depths (2.5–4.5 cm), (3) an upgraded treatment planning and control software with safety features such as reflectivity index measurement (RIMTM) and transducer tissue measurement (TTMTM); and (4) 3-D volume image rendering of the prostate. The SonablateTM 500 platform was tested in an in vivo canine experimental study in which the entire prostate was ablated. The prostate ultrasound images before and post HIFU treatment show very good correlation to the planned lesion. Histology delineated ...
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Papers by Thomas Gardner