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Dive into the research topics where Jonathan J. Lewis is active.

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Featured researches published by Jonathan J. Lewis.


Annals of Surgery | 2000

Two Hundred Gastrointestinal Stromal Tumors: Recurrence Patterns and Prognostic Factors for Survival

Ronald P. DeMatteo; Jonathan J. Lewis; Denis H. Y. Leung; Satvinder S. Mudan; James M. Woodruff; Murray F. Brennan

OBJECTIVE To analyze the outcome of 200 patients with gastrointestinal stromal tumor (GIST) who were treated at a single institution and followed up prospectively. SUMMARY BACKGROUND DATA A GIST is a visceral sarcoma that arises from the gastrointestinal tract. Surgical resection is the mainstay of treatment because adjuvant therapy is unproven. METHODS Two hundred patients with malignant GIST were admitted and treated at Memorial Hospital during the past 16 years. Patient, tumor, and treatment variables were analyzed to identify patterns of tumor recurrence and factors that predict survival. RESULTS Of the 200 patients, 46% had primary disease without metastasis, 47% had metastasis, and 7% had isolated local recurrence. In patients with primary disease who underwent complete resection of gross disease (n = 80), the 5-year actuarial survival rate was 54%, and survival was predicted by tumor size but not microscopic margins of resection. Recurrence of disease after resection was predominantly intraabdominal and involved the original tumor site, peritoneum, and liver. CONCLUSIONS GISTs are uncommon sarcomas. Tumor size predicts disease-specific survival in patients with primary disease who undergo complete gross resection. Tumor recurrence tends to be intraabdominal. Investigational protocols are indicated to reduce the rate of recurrence after resection and to improve the outcome for patients with GIST.


Annals of Surgery | 1998

Retroperitoneal soft-tissue sarcoma : analysis of 500 patients treated and followed at a single institution

Jonathan J. Lewis; Denis H. Y. Leung; James M. Woodruff; Murray F. Brennan

OBJECTIVE To analyze treatment and survival of a large cohort of patients with retroperitoneal soft-tissue sarcomas (STS) treated and prospectively followed at a single institution. SUMMARY BACKGROUND DATA Retroperitoneal STS are relatively uncommon and constitute a difficult management problem. Although surgical resection is often difficult or impossible, current chemotherapy is not effective and radiation is limited by toxicity to adjacent structures. Thus, complete surgical resection remains the most effective modality for selected primary and recurrent disease. METHODS Five hundred patients with retroperitoneal STS were admitted and treated between July 1, 1982, and September 30, 1997, and prospectively followed. Patient, tumor, and treatment variables were analyzed for disease-specific and disease-free survival. Survival was determined with the Kaplan-Meier method. Statistical significance was evaluated using the logrank test for univariate influence and Cox model stepwise regression for multivariate influence. RESULTS Two hundred seventy-eight patients (56%) had primary disease and 222 (44%) recurrent disease. Median follow-up was 28 months (range 1 to 172 months), 40 months for survivors. Median survival was 72 months for patients with primary disease, 28 months for those with local recurrence, and 10 months for those with metastasis. For patients with primary or locally recurrent tumors, unresectable disease, incomplete resection, and high-grade tumors significantly reduced survival time. CONCLUSIONS In this study of patients with retroperitoneal STS, stage at presentation, high histologic grade, unresectable primary tumor, and positive gross margin are strongly associated with the tumor mortality rate. Patients approached with curative intent should undergo aggressive attempts at complete surgical resection. Incomplete resection should be undertaken only for symptom relief.


Cancer | 2002

Clinicopathologic correlates of solitary fibrous tumors.

Jason S. Gold; Cristina R. Antonescu; Cristina Hajdu; Cristina R. Ferrone; B S Mustafa Hussain; Jonathan J. Lewis; Murray F. Brennan; Daniel G. Coit

Solitary fibrous tumors (SFTs) are rare fibrous neoplasms. Since their initial description as arising from the pleura, SFTs have been reported at a wide range of anatomic sites. To the authorss knowledge, there are no large series reporting both thoracic and extrathoracic SFTs nor are there any large series that analyze clinicopathologic correlates of tumor behavior.


Journal of Clinical Oncology | 2002

Vaccination of Metastatic Melanoma Patients With Autologous Tumor-Derived Heat Shock Protein gp96-Peptide Complexes: Clinical and Immunologic Findings

Filiberto Belli; Alessandro Testori; Licia Rivoltini; Michele Maio; Giovanna Andreola; Mario Roberto Sertoli; Gianfrancesco Gallino; Adriano Piris; Alessandro Cattelan; Ivano Lazzari; Matteo Carrabba; Giorgio Scita; Cristina Santantonio; Lorenzo Pilla; Gabrina Tragni; Claudia Lombardo; Alfonso Marchianò; Paola Queirolo; Francesco Bertolini; Agata Cova; Elda Lamaj; Lucio Ascani; Roberto Camerini; Marco Corsi; Natale Cascinelli; Jonathan J. Lewis; Pramod K. Srivastava; Giorgio Parmiani

PURPOSE To determine the immunogenicity and antitumor activity of a vaccine consisting of autologous, tumor-derived heat shock protein gp96-peptide complexes (HSPPC-96, Oncophage; Antigenics, Inc, Woburn, MA) in metastatic (American Joint Committee on Cancer stage IV) melanoma patients. PATIENTS AND METHODS Sixty-four patients had surgical resection of metastatic tissue required for vaccine production, 42 patients were able to receive the vaccine, and 39 were assessable after one cycle of vaccination (four weekly injections). In 21 patients, a second cycle (four biweekly injections) was given because no progression occurred. Antigen-specific antimelanoma T-cell response was assessed by enzyme-linked immunospot (ELISPOT) assay on peripheral blood mononuclear cells (PBMCs) obtained before and after vaccination. Immunohistochemical analyses of tumor tissues were also performed. RESULTS No treatment-related toxicity was observed. Of 28 patients with measurable disease, two had a complete response (CR) and three had stable disease (SD) at the end of follow-up. Duration of CR was 559+ and 703+ days, whereas SD lasted for 153, 191, and 272 days, respectively. ELISPOT assay with PBMCs of 23 subjects showed a significantly increased number of postvaccination melanoma-specific T-cell spots in 11 patients, with clinical responders displaying a high frequency of increased T-cell activity. Immunohistochemical staining of melanoma tissues from which vaccine was produced revealed high expression of both HLA class I and melanoma antigens in seven of eight clinical responders (two with CR, three with SD, and the three with long-term disease-free survival) and in four of 12 nonresponders. CONCLUSION Vaccination of metastatic melanoma patients with autologous HSPPC-96 is feasible and devoid of significant toxicity. This vaccine induced clinical and tumor-specific T-cell responses in a significant minority of patients.


Annals of Surgery | 2002

Analysis of the prognostic significance of microscopic margins in 2,084 localized primary adult soft tissue sarcomas.

Alexander Stojadinovic; Denis H. Y. Leung; Axel Hoos; David P. Jaques; Jonathan J. Lewis; Murray F. Brennan

ObjectiveTo define the significance of positive microscopic resection margins in a large cohort treated for soft tissue sarcoma. MethodsThe authors analyzed 2,084 patients with localized primary soft tissue sarcoma (all anatomic sites) treated from 1982 to 2000. Clinicopathologic variables studied included tumor site, size, depth, histologic type, grade, and resection margin status. Treatment other than resection was not analyzed. Study endpoints included local and distant recurrence-free and disease-specific survival rates, estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed using the log-rank test and the Cox proportional hazards model. ResultsMedian follow-up was 50 months. After primary resection, 1,624 (78%) patients had negative and 460 (22%) had positive resection margins. Having positive margins nearly doubled the risk of local recurrence and increased the risk of distant recurrence and disease-related death. Seventy-two percent of patients with positive margins had no recurrence. Resection margin did not predict local control for retroperitoneal sarcomas or fibrosarcomas. Resection margin remained significantly associated with distant recurrence-free survival and disease-specific survival across all subsets after adjusting for other prognostic variables. The overall 5-year disease-specific survival rates for negative and positive margins were 83% and 75%. ConclusionsPositive microscopic resection margins significantly decrease the local recurrence-free survival rate for other-than-primary fibrosarcoma and retroperitoneal sarcomas, and independently predict distant recurrence-free survival rates and disease-specific survival rates for all patient subsets. Adjuvant therapy should be considered in the management of soft tissue sarcoma to increase local control. Because 72% of positive margins did not equate with inevitable local recurrence, considerable clinical judgment is required in considering additional treatment. Microscopic resection margins should be considered for inclusion in staging systems and treatment algorithms that address local recurrence.


American Journal of Pathology | 2001

Validation of Tissue Microarrays for Immunohistochemical Profiling of Cancer Specimens Using the Example of Human Fibroblastic Tumors

Axel Hoos; Marshall J. Urist; Alexander Stojadinovic; Stephen Mastorides; Maria E. Dudas; Denis H. Y. Leung; David Kuo; Murray F. Brennan; Jonathan J. Lewis; Carlos Cordon-Cardo

Tissue microarrays allow high-throughput molecular profiling of cancer specimens by immunohistochemistry. Phenotype information of sections from arrayed biopsies on a multitissue block needs to be representative of full sections, as protein expression varies throughout the entire tumor specimen. To validate the use of tissue microarrays for immunophenotyping, we studied a group of 59 fibroblastic tumors with variable protein expression patterns by immunohistochemistry for Ki-67, p53, and the retinoblastoma protein (pRB). Data on full tissue sections were compared to the results of one, two, and three 0.6-mm core biopsies per tumor on a tissue array. Ki-67 and p53 staining was read as two categories (positive or negative). Concordance for this staining between tissue arrays with triplicate cores per tumor and full sections were 96 and 98%, respectively. For pRB staining was read as three categories (high, moderate, or negative), where concordance was 91%. The use of three cores per tumor resulted in lower numbers of lost cases and lower nonconcordance with standard full sections as compared to one or two cores per tumor. Correlations between phenotypes and clinical outcome were not significantly different between full section and array-based analysis. Triplicate 0.6-mm core biopsies sampled on tissue arrays provide a reliable system for high-throughput expression profiling by immunohistochemistry when compared to standard full sections. Triplicate cores offer a higher rate of assessable cases and a lower rate of nonconcordant readings than one or two cores. Concordance of triplicate cores is high (96 to 98%) for two category distinction and decreases with the complexity of the phenotypes being analyzed (91%).


International Journal of Cancer | 2000

IMMUNIZATION OF CANCER PATIENTS WITH AUTOLOGOUS CANCER-DERIVED HEAT SHOCK PROTEIN gp96 PREPARATIONS: A PILOT STUDY

Sylvia Janetzki; Dirk Palla; Valentino Rosenhauer; Heribert Lochs; Jonathan J. Lewis; Pramod K. Srivastava

Heat shock protein (HSP)–peptide complexes isolated from murine cancers elicit protective immunity and T lymphocytes specific for the cancer from which the HSPs are isolated. A pilot study was designed to test the feasibility, immunogenicity and toxicity of such treatment in cancer patients. Sixteen patients with assorted advanced malignancies, which had become refractory to established therapies, were recruited. The gp96 vaccine was prepared for each patient from tumor obtained from that patient. Anti‐tumor immune responses were evaluated using Elispot assays of T cells in peripheral blood after minimal in vitro stimulation. No unacceptable vaccine‐related toxicities or auto‐immune reactions were observed. Immunization with autologous gp96 elicited MHC I–restricted, tumor‐specific CD8+ T lymphocytes in 6/12 patients immunized. In addition, expansion of the NK cell population was seen in 8/13 of patients immunized. These observations are entirely consistent with the murine experience and form a firm basis for future trials with clinical end points, using autologous, patient‐specific HSP–peptide vaccines. Int. J. Cancer 88:232–238, 2000.


Journal of Clinical Oncology | 1997

Prognostic factors associated with long-term survival for retroperitoneal sarcoma: implications for management.

Martin J. Heslin; Jonathan J. Lewis; Evan Nadler; Elliot Newman; James M. Woodruff; Ephraim S. Casper; Denis H. Y. Leung; Murray F. Brennan

PURPOSE Retroperitoneal soft tissue sarcomas are rare tumors. Studies characterizing long-term follow-up and patterns of recurrence are limited. The purpose of this analysis is to identify patterns of recurrence and prognostic factors associated with long-term survival after resection of retroperitoneal soft tissue sarcomas. METHODS Between July 1, 1982, and June 30, 1990, 198 adult patients were identified from our prospective soft tissue sarcoma database carrying the diagnosis of retroperitoneal soft tissue sarcoma who were eligible for > or = 5 years of follow-up. Of these, 48 patients (25%) were documented to be alive > or = 5 years from the time of operation. Statistical analysis was by log-rank or Wilcoxon test for univariate analysis. Multivariate analysis was by the Cox model. RESULTS The recurrence rate during the follow-up period was approximately 5% per year from the time of initial operation. Of the patients who were disease-free for > or = 5 years from initial surgery, 40% recurred by 10 years. Radiation therapy was the only factor significant (P = .02) for a reduction in the risk of local recurrence. Age < or = 50 years and high-grade tumors were significant factors (P = .003 and .009, respectively) for an increased risk of distant metastasis. Incomplete gross resection was the only factor significant for an increased risk of tumor mortality (P = .003). CONCLUSION Complete surgical resection at the time of primary presentation is likely to afford the best chance for long-term survival. With long-term follow-up, it is clear that recurrence will continue to occur, and a 5-year disease-free interval is not a cure. Patients with an incomplete initial resection, age less than 50 years, and high-grade tumors are candidates for investigational adjuvant therapy.


Annals of Surgery | 1999

The Enigma of Desmoid Tumors

Jonathan J. Lewis; Patrick J. Boland; Dennis Leung; James M. Woodruff; Murray F. Brennan

OBJECTIVE To analyze patients with recurrent extremity desmoids, in whom the surgical therapeutic option was either major amputation or observation. SUMMARY BACKGROUND DATA The biology and natural history of desmoid tumors are an enigma. These tumors invade surrounding structures and recur locally but do not metastasize. The morbidity of treating these tumors in the context of their relatively benign biology is uncertain. METHODS Between July 1982 and June 1998, the authors treated and prospectively followed 206 patients with extremity desmoid tumors. All patients underwent standardized surgical resection, the surgical goal always being complete resection with negative margins. When tumors recurred, they were evaluated for reresection. Amputation was considered when resection was not possible because of neurovascular or major bone involvement, or in the presence of a functionless, painful extremity. RESULTS During this period, 22 patients had disease that was not resectable without amputation. This was out of a total of 115 patients with primary disease and 91 patients with recurrent disease. All recurrences were local; in no patient did metastasis develop. In this group of 22 patients with unresectable disease, 7 underwent amputation and 15 did not. These 15 patients were followed, alive with disease, having no surgical resection. Four patients received systemic treatment with tamoxifen and nonsteroidal antiinflammatories, three received systemic cytotoxic chemotherapy, and two received both tamoxifen and chemotherapy. Six patients received no systemic treatment. The range of follow-up was 25 to 92 months. In all patients, there was no or insignificant tumor progression; in three patients who underwent observation alone, there was some regression of tumor. During follow-up, no patient has required subsequent amputation, and no patient has died from disease. CONCLUSIONS In desmoid tumors, aggressive attempts at achieving negative resection margins may result in unnecessary morbidity. Function- and structure-preserving procedures should be the primary goal. In select patients, whose only option is amputation, it may be prudent to observe them with their limb and tumor intact.


Cancer | 1999

The management of unicentric and multicentric Castleman's disease

Wilbur B. Bowne; Jonathan J. Lewis; Daniel A. Filippa; Ruben Niesvizky; Ari D. Brooks; Michael Burt; Murray F. Brennan

Castlemans disease (CD), or angiofollicular lymph node hyperplasia, creates both diagnostic and therapeutic dilemmas for most physicians. For patients with this rare and poorly understood disease, the optimal therapy is unknown. The authors report their experience during the years 1986–1997 with this uncommon clinicopathologic entity.

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Murray F. Brennan

Memorial Hospital of South Bend

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Denis H. Y. Leung

Memorial Sloan Kettering Cancer Center

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Alan N. Houghton

Memorial Sloan Kettering Cancer Center

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Wilbur B. Bowne

Memorial Sloan Kettering Cancer Center

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William G. Hawkins

Washington University in St. Louis

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Jason S. Gold

Brigham and Women's Hospital

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