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Featured researches published by Laurie Tuason.


Head and Neck-journal for The Sciences and Specialties of The Head and Neck | 1997

A phase III randomized trial comparing concurrent chemotherapy and radiotherapy with radiotherapy alone in resectable stage III and iv squamous cell head and neck cancer: Preliminary results

David J. Adelstein; Jerrold P. Saxton; Pierre Lavertu; Laurie Tuason; Benjamin G. Wood; John R. Wanamaker; Isaac Eliachar; Marshall Strome; Marjorie A. Van Kirk

A phase III randomized comparison of radiotherapy alone versus combination chemotherapy and concurrent continuous‐course radiotherapy was performed at the Cleveland Clinic Foundation.


Urology | 1994

Impact of bladder neck preservationduring radical prostatectomy on continence and cancer control

Mark R. Licht; Eric A. Klein; Laurie Tuason; Howard S. Levin

OBJECTIVES To assess the effect of preservation of the bladder neck and other factors on the rate of postoperative urinary continence and cancer control after radical prostatectomy. METHODS Prospective analysis of clinical and pathologic findings in 206 consecutive patients undergoing radical prostatectomy with a surgical technique that emphasizes preservation of periurethral supporting tissue, urethral length, incorporation of the posterior periurethral fascia into the vesicourethral anastomosis, and preservation of the bladder neck. RESULTS Uni- and multivariate statistical analysis demonstrated that patient age (p = 0.033) and vesical neck contracture (p = 0.047) were predictive of incomplete return of urinary control. Preservation of the vesical neck had no impact on return of continence, but was associated with a trend to a lower incidence of vesical neck contractures. A positive bladder neck margin occurred in 6.8% of surgical specimens and was associated with a higher grade, more advanced local stage, and other positive margins in all cases. The rate of local recurrence or prostate-specific antigen (PSA)-only failure was similarly independent of whether the vesical neck was preserved or resected and reconstructed. CONCLUSIONS Age greater than 65 and occurrence of a vesical neck contracture are adverse predictors for return of urinary continence after radical prostatectomy. Preservation of the bladder neck does not have an impact on return of urinary control but may be associated with a lower risk of vesical neck contracture. Preservation of the bladder neck does not compromise cancer control as assessed by local or PSA-only failure rates.


Journal of Immunotherapy | 1994

Characterization of tumor-infiltrating lymphocyte subsets from human renal cell carcinoma: Specific reactivity defined by cytotoxicity, interferon-γ secretion, and proliferation

James H. Finke; Patricia Rayman; Laura Hart; Jeannine Alexander; Mark Edinger; Raymond R. Tubbs; Eric A. Klein; Laurie Tuason; Ronald M. Bukowski

The detection of T cells with specificity for human renal cell carcinoma (RCC) has been difficult to document. In an attempt to improve our identification of RCC-reactive T cells, tumor-infiltrating lymphocytes (TIL) were expanded in interleukin-2/interleukin-4 (IL-2/IL-4) and then separated into CD4+ and CD8+ subsets using antibody-coated biomagnetic beads. TIL grown in IL-2/IL-4 expanded to greater numbers than TIL grown in IL-2 alone. From 16 patients in whom subset separation was performed, three CD4+ and three CD8+ TIL consistently had specificity for RCC that was detected by cytotoxicity, proliferation, or interferon-gamma (IFN-gamma) production. Four of the six lines were derived from the IL-2/IL-4 cultures. Two CD8+ TIL lines displayed specific lytic activity, lysing the autologous tumor but not allogeneic RCC or nonrenal tumors. Moreover, the lytic activity of these lines was blocked by anti-CD3 antibody, suggesting that tumor recognition was through the TCR/CD3 complex. Two additional TIL lines showed preferential lysis of RCC because they were cytotoxic for autologous tumor and one or more allogeneic RCC but not other tumor types. Two nonlytic CD4+ lines as well as the two CD8+ lines that were specifically lytic also produced IFN-gamma in response to the autologous tumor but not allogeneic RCC. Although these TIL lines produce IFN-gamma when stimulated with tumor alone, the addition of 5 U/ml of IL-2 significantly enhanced IFN-gamma secretion. The four TIL lines that showed specificity for RCC in terms of IFN-gamma production also had enhanced proliferation to the autologous RCC plus IL-2 but not to multiple allogeneic RCC plus IL-2. These studies demonstrate that TIL from RCC patients contain both CD4+ and CD8+ T cells that have specificity for RCC. In addition to cytotoxicity, specificity to RCC can be defined by IFN-gamma production and proliferation.


Urology | 1998

Initial dissection of the lateral fascia reduces the positive margin rate in radical prostatectomy.

Eric A. Klein; Patrick A. Kupelian; Laurie Tuason; Howard S. Levin

OBJECTIVES Positive margins predict an adverse outcome after radical retropubic prostatectomy (RRP). The effect of initial incision of the lateral pelvic fascia prior to urethral transection on positive margins rates is assessed. METHODS The rate of positive margins in 350 consecutive RRPs is compared in two groups without hormonal pretreatment. In group 1 (n = 198), RRP was performed in standard fashion with apical dissection and urethral transection preceding dissection of the lateral pelvic fascia and mobilization of the prostate from the anterior rectal surface. In group 2 (n = 1 52), the initial step consisted of incision of the lateral pelvic fascia along the perirectal surface with prostatic mobilization off the rectum prior to urethral transection. The bladder neck and seminal vesicle dissection was identical in both groups. Specimens were step-sectioned for histologic analysis. Differences in rates of positive margins were analyzed by Fishers exact test and logistic regression. RESULTS The rate of positive margins was reduced from 37.4% in group 1 to 15.8% in group 2. In the logistic regression model, surgical technique, Gleason sum, serum prostate-specific antigen (PSA), and the presence of extracapsular extension were independent predictors of margin status, with group 1 being more than twice as likely to have positive margins than group 2 (P = 0.0076; odds ratio 2.198; 95% confidence interval 1.23 to 3.92). The rate of positive margins was reduced from 45.5% in group 1 to 16.7% in group 2 (P = 0.0046) for non-nerve-sparing RRP and from 33.3% to 15.5% (P = 0.0012) for nerve-sparing RRP. There were no differences in functional outcomes between groups and no rectal injuries in group 2. CONCLUSIONS Initial dissection of the lateral pelvic fascia during RRP results in a lower rate of positive margins independent of tumor grade, clinical stage, extracapsular extension, and preoperative PSA level.


Journal of Immunotherapy | 1997

Phase II trial of interleukin-2 and interferon-α in patients with renal cell carcinoma : Clinical results and immunologic correlates of response

Ronald M. Bukowski; Thomas Olencki; Qiu Wang; David M. Peereboom; G T Budd; Paul Elson; Kate Sandstrom; Laurie Tuason; Patricia Rayman; Raymond R. Tubbs; D. McLain; Eric A. Klein; Andrew C. Novick; James H. Finke

A phase II trial was conducted in patients with metastatic renal cell carcinoma, to assess the clinical efficacy and immunoregulatory effects of continuous-infusion recombinant interleukin-2 (rIL-2) (9.0 x 10(6) IU/m2/day on days 1-5, 8-12, 15-19, and 22-26) and subcutaneously administered recombinant human interferon-alpha 2b (rHuIFN alpha 2b) (10.0 x 10(6) U/m2/day TIW). Thirty-six patients with metastatic renal cell carcinoma, performance status of 0-1, and measurable disease who had not received prior rIL-2, rHuIFN alpha 2b, or chemotherapy were treated. Patients with CNS metastases, active infections, history of another malignancy within 3 years, and those requiring corticosteroids were ineligible. Cycles of rIL-2 and rHuIFN alpha 2b were administered in the outpatient department every 6-8 weeks in stable or responding patients until patient tolerance or a complete response were reached. Doses were modified for grade III or IV toxicity. Ancillary studies included three-color immunocytometric analysis of peripheral blood lymphocytes, repetitive tumor biopsies for immunohistologic analysis of infiltrating cells and proliferative responses of tumor infiltrating lymphocytes, and preliminary studies of changes in peripheral blood T-lymphocyte signal transduction molecules [T-cell receptor (TCR)-zeta, p56ick, p59fyn]. Thirty-six eligible patients were treated, with 6 of 36 patients (17%, 95% confidence interval 6-33%) responding (3 complete response, 3 partial response). In two of the partial responders, and in an additional three patients with either minimal tumor regression (one patient) or stable disease (two patients), surgical removal of residual disease was undertaken. The median survival of all patients was 14 months. The toxicity of this regimen was severe, but outpatient administration was possible in most instances. Immunoregulatory effects on T-cell subsets included increases in various CD3+ CD25+/- HLADr+/- subsets unrelated to response. Tumor biopsies before and/or during therapy were obtained in 17 patients, and no consistent alterations in the degree of T-lymphocyte or macrophage infiltrates could be detected. In a subset of patients, tumor infiltrating lymphocyte proliferative responses and levels of peripheral blood T-cell signal transduction molecules (TCR-zeta, p56lck, p59fyn) were investigated. Abnormalities were found in selected patients, which improved during rIL-2/rHuIFN alpha 2b therapy. This cytokine combination produces tumor regression in selected patients with metastatic renal cell carcinoma. Surrogate immunologic markers associated with response were not identified; however, preliminary studies demonstrate investigation of immune defects and their reversal with cytokine therapy is possible.


American Journal of Clinical Oncology | 1995

High-dose busulfan and cyclophosphamide followed by autologous bone marrow transplantation and/or peripheral blood progenitor cell rescue for metastatic breast cancer.

Matt Kalaycioglu; Alan E. Lichtin; Steven Andresen; Laurie Tuason; Brian J. Bolwell

High doses of combination alkylating agents have shown promise in the treatment of breast cancer but are complicated by significant toxicity. Busulfan and Cyclophosphamide (BuCy) is a high-dose combination alkylating agent regimen that is well-tolerated when given for hematologic malignancy. We prospectively studied the effects of BuCy followed by autologous bone marrow transplant (ABMT) or peripheral blood progenitor cell (PBPC) rescue in 21 patients with metastatic breast cancer who had responded to either standard chemotherapy or radiotherapy. The mean patient age was 44 years. Nine patients were either estrogen- or progesterone-receptor positive, ten were negative, and two were unknown. Fourteen patients had local recurrence, ten had bone metastases, six had visceral disease, and two had a nonlocal soft tissue recurrence. Busulfan 16 mg/kg and Cyclophosphamide 120 mg/kg (BuCy2) was given and followed by either ABMT, PBPC rescue, or both. Grade III to IV extramyeloid toxicity occurred in 6 (29%) patients. One patient died of hepatic venoocclusive disease but there was no other treatment-related mortality. Pulmonary infiltrates with hypoxia of uncertain origin developed in 2 patients after discharge. Of the 10 patients with measurable disease, 4 had complete responses, and 3 had partial responses to high-dose therapy for a total response rate of 70%. The estimated 2-year disease- free survival is 25% (95% CI = 6% to 44%). Our study found BuCy to be a well-tolerated preparative regimen for ABMT in the treatment of patients with metastatic breast cancer.


Journal of Immunotherapy | 1994

Phase I Trial of Cisplatin, WR-2721, and the Murine Monoclonal Antibody R24 in Patients with Metastatic Melanoma: Clinical and Biologic Effects

Ronald M. Bukowski; S. A. Murthy; James H. Finke; M. J. Caulfield; Raymond R. Tubbs; P. Herzog; Jill Stanley; Mark Edinger; Laurie Tuason; D. McLain; G T Budd; Thomas Olencki; Ram Ganapathi

The therapeutic and biologic effects of murine monoclonal antibodies in patients with malignancies have been widely investigated. Attempts to enhance results by combining these agents with cytotoxic drugs are now under study. A Phase I trial was performed to assess the toxicity and biologic effects of escalating doses of R24 (0-40 mg/m2/day 1-5, 8-12), an antibody that binds to the ganglioside GD3 present on melanoma cells, administered in combination with cisplatin (120 mg/m2) and WR-2721 (740 mg/m2) on day 1. Twenty-three patients with metastatic malignant melanoma were treated and are evaluable. The true maximum tolerated dose of R24 given as part of this combination was not reached. The toxicity of the regimen was moderate and included fever and urticaria, which were attributed to R24. Severe but reversible renal failure was noted in six patients in subsequent (two or more) treatment cycles, but when cisplatin was administered in 3% saline, this toxicity was not seen. Responses were seen in 2 of 19 patients receiving all three agents and in 1 of 4 patients receiving only cisplatin and WR-2721. No significant enhancement of natural killer, lymphokine-activated killer, and antibody-dependent cellular cytotoxicity lytic activity or significant changes from baseline in lymphocyte subsets secondary to R24 were seen. In 4 of 10 patients tumor localization of mouse monoclonal antibody was found and appeared greatest at higher R24 doses and during week 1 of therapy. Human anti-mouse antibody responses developed by day 22 in 17 of 19 patients treated with R24, and the coadministration of cisplatin did not appear to abrogate this response. Finally, the half-life and Cmax of cisplatin were not affected by R24. In summary, the combination was well tolerated, responses were few, and significant biologic interactions or immunomodulation were not observed.


Journal of Immunotherapy | 1996

Immunomodulatory effects of interleukin-2 and interleukin-4 in patients with malignancy

Thomas Olencki; James H. Finke; Raymond R. Tubbs; Laurie Tuason; T. Greene; D. McLain; S. J. Swanson; P. Herzog; Jill Stanley; Mark Edinger; G T Budd; Ronald M. Bukowski

A phase I trial of simultaneously administered recombinant interleukin-2 (rIL-2) and recombinant human IL-4 (rHuIL-4) was conducted to evaluate the toxicity and the clinical and immunologic effects of this cytokine combination. Thirty-nine eligible patients with refractory malignancy were treated at eight different dose levels (1A to 3B): 1-3 of rIL-2 [3.0, 12.0, and 48.0 x 10(6) IU/m(2) i.v. three times weekly (TIW)] and A-C of rHuIL-4 (40, 120, and 400 mu g/m(2) s.c. TIW). The toxicity of these two cytokines was moderate and was comparable with that seen with rIL-2 alone. The maximal tolerated dose (MTD) of the combination was not reached because of lack of sufficient rHuIL-4 but is at least 48.0 x 10(6) IU/m(2) of rIL-2 and 120 mu g/m(2) of rHuIL-4. Two patients with melanoma had partial responses. The immunologic effects included increases in absolute lymphocyte numbers, and the CD3- /CD56+/ CD2+, total CD56+, CD8+, and CD16c+ lymphocyte subsets with increasing rIL-2 dose levels, but not with rHuIL-4. This increase in natural killer (NK) cells in the peripheral blood was accompanied by an increase over baseline in NK lytic activity against K562 targets; however, concomitant increases in lymphokine-activated killer (LAK) activity (Daudi targets) were not seen. The CD3+, CD4+, and CD3+/CD25+/HLA-Dr+ T-cell subsets also increased, and these increases were related to both increasing rIL-2 and rRuIL-4 doses. Finally, in four of six patients, serial tumor biopsies demonstrated increases in major histocompatibility complex (MHC) class I or II antigen expression on tumor cells or increasing T-cell infiltrates during cytokine therapy or both. This trial demonstrated that rIL-2 and rHuIL-4 can be administered simultaneously with acceptable toxicity. The immunologic findings demonstrated the expected rIL-2-associated increases of CD56+ and CD16c+ lymphocytes and NK activity, and interestingly, no development of LAK activity. These findings suggest regulatory effects of rHuIL-4 on rIL-2-related effects in vivo.


Archive | 1995

Cytokine Therapy of Metastatic Renal Cell Carcinoma: The Cleveland Clinic Experience

Ronald M. Bukowski; Thomas Olencki; David M. Peereboom; G. T. Budd; Sudish C. Murthy; Raymond R. Tubbs; Patricia Rayman; D. McLain; Eric A. Klein; Laurie Tuason; James H. Finke

The incidence of renal cell carcinoma in the United States appears to be increasing, and in 1994 will cause an estimated 11,300 deaths (1). Patients with resectable disease have a five year survival of approximately 50% (2), and those individuals presenting with regionally advanced or metastatic disease have five year survival rates of less than 5% (3). The rare spontaneous regression of established metastatic disease (4) has produced speculation that host factors may be relevant in controlling tumor growth. Recently, studies demonstrating the presence of specific cytolytic T-lymphocytes in tumor infiltrating lymphocytes isolated from renal cancers (5, 6) have documented the existence of a host immune response to this tumor. In the 1980’s, the clinical use of first recombinant interferon alpha (7) and subsequently interleukin-2 (rIL-2) (8, 9) was investigated in patients with metastatic renal cell carcinoma. The clear demonstration of objective tumor regressions secondary to administration of these cytokines has been followed by a period of increasing interest in the use of various biologic response modifiers in this neoplasm. At The Cleveland Clinic Foundation, we have systematically evaluated the biologic and clinical effects of various cytokines in patients with malignancy during the past 15 years. The purpose of this report is to summarize the experience in patients with metastatic renal cell cancer.


Cancer Research | 1993

T-Cells Infiltrating Renal Cell Carcinoma Display a Poor Proliferative Response Even Though They Can Produce Interleukin 2 and Express Interleukin 2 Receptors

Jeannine Alexander; Seiji Kudoh; Kathryn A. Melsop; Thomas A. Hamilton; Mark Edinger; Raymond R. Tubbs; Dante Sica; Laurie Tuason; Eric A. Klein; Ronald M. Bukowski; James H. Finke

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G T Budd

Case Western Reserve University

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