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G D Demetri

Publications and source records attributed to G D Demetri.

At least 37 records · Page 2Linked to original sources
PubMed1999

Adults with Ewing's sarcoma/primitive neuroectodermal tumor: adverse effect of older age and primary extraosseous disease on outcome.

OBJECTIVE: To assess outcome and prognostic factors for survival of adults with Ewing's sarcoma/primitive neuroectodermal tumor (PNET). BACKGROUND: Ewing's sarcoma/PNET is a disease of childhood rarely seen in adults. Accordingly, there is a relative paucity of published literature pertaining to outcome for adults with this disease. METHODS: Between 1979 and 1996, 37 patients with newly diagnosed Ewing's sarcoma/PNET were evaluated and treated at the Adult Sarcoma Program at Dana-Farber Cancer Institute and Brigham & Women's Hospital. Twenty-six patients had localized disease at presentation and 11 had metastatic disease. All but two patients received multiagent chemotherapy. Local treatment consisted of surgery (7 patients), surgery and radiation therapy (19), radiation therapy (6), or no local treatment (5). Median follow-up for living patients was 100 months (range 8 to 199). RESULTS: The 5-year survival rate for the group overall was 37%+/-9%. The 5-year local control rate was 85%+/-7%. Significant favorable predictors for survival on univariate analysis included localized disease at presentation, primary origin in bone, primary size <8 cm, and a favorable objective response to chemotherapy. Patients with localized disease had a 5-year survival rate of 49%+/-11% compared with 0% for those with metastatic disease at presentation. Multivariate analysis showed three significant independent predictors for death: metastatic disease at presentation, primary origin in extraosseous tissue versus bone, and age 26 years or older. CONCLUSION: Adult patients with Ewing's sarcoma/PNET at highest risk for death are those who are older than 26 years and have metastatic disease or an extraosseous primary tumor. The development of novel therapies should target these high-risk groups.

Adolescent↗
PubMed1999

Long-term outcomes after function-sparing surgery without radiotherapy for soft tissue sarcoma of the extremities and trunk.

PURPOSE: To define the rate of local recurrence (LR) and identify prognostic factors for LR for patients with soft tissue sarcoma (STS) treated with function-sparing surgery (FSS) without radiotherapy (RT). PATIENTS AND METHODS: Between 1970 and 1994, 242 patients with STS of the trunk and extremity presented with primary localized disease, 74 of whom were treated with FSS without RT (31%). The median tumor size was 4 cm (range, 0.5 to 31 cm). There were 40 patients with grade 1 tumors and 34 with grade 2 and 3 tumors. Median follow-up was 126 months. RESULTS: The 10-year actuarial local control rate was 93% +/- 4%. Resection margin status was a significant predictor for LR. Patients with closest histologic resection margins of less than 1 cm had a 10-year local control rate of 87% +/- 6% compared with 100% for patients with closest histologic resection margins of >/= 1 cm (P =.04). There was no significant association between LR and tumor grade, size, site (truncal v extremity), or depth (superficial v deep). For all patients, the 10-year actuarial survival rate was 73% +/- 6%. CONCLUSION: The 7% LR rate after treatment of STS with FSS without RT reported herein is comparable to published rates following treatment where adjuvant RT is used. These results suggest there may be a select subset of patients with STS in whom carefully performed FSS may serve as definitive therapy and in whom adjuvant RT may not be necessary. However, further study is needed to carefully define this subset of patients and to identify the optimal surgical approach and technique for patients treated without RT.

Adult↗
PubMed1998

Major developments in the understanding and treatment of soft-tissue sarcomas in adults.

Soft-tissue sarcomas in adults comprise less than 1% of human malignancies by incidence, yet this class of tumors is highly visible in the oncology research literature. Great strides are being made in the understanding of this heterogeneous class of cancers of mesenchymal origin. A better understanding of the benefits and limitations of current therapeutic strategies for sarcomas accompanies this improved understanding of the diseases. In this review, key developments from 1997 are presented and discussed, including the most recent data analyzing the use of adjuvant chemotherapy. Other relevant topics include new prognostic factors for sarcomas, research in new drugs, the chemotherapy dose-response relationship, and novel biological insights into sarcomas, which are spurring research regarding nontoxic differentiation therapy for this disease.

Adult↗
PubMed1998

Quality-of-life benefit in chemotherapy patients treated with epoetin alfa is independent of disease response or tumor type: results from a prospective community oncology study. Procrit Study Group.

PURPOSE: To evaluate prospectively the effectiveness of epoetin alfa as an adjunct to chemotherapy in patients with cancer based on changes in quality-of-life parameters and hemoglobin levels, and to correlate these changes with antitumor response. PATIENTS AND METHODS: Two thousand three hundred seventy patients with nonmyeloid malignancies who received chemotherapy were enrolled onto this study from 621 US community-based practices. Patients received epoetin alfa 10,000 U three times weekly, which could be increased to 20,000 U three times weekly depending on the hemoglobin response at 4 weeks. Treatment continued for a maximum of 16 weeks in patients who showed evidence of hematologic response. RESULTS: Two thousand two hundred eighty-nine patients (97%) were eligible for efficacy analyses. Epoetin alfa therapy was associated with improved quality-of-life parameters; these improvements correlated significantly with hemoglobin levels and were independent of tumor response. Provider-reported Karnofsky performance scores did not correlate with the improved quality-of-life changes. Epoetin alfa therapy was also associated with a significant increase in hemoglobin levels and decrease in transfusion use. Tumor type, chemotherapy agent/regimen, prior chemotherapy, baseline hemoglobin level, and baseline erythropoietin level were not predictive of a positive response to treatment. Epoetin alfa was well tolerated. CONCLUSION: Epoetin alfa appears to have a beneficial impact on patient-reported functional capacity and quality of life in patients with cancer who received chemotherapy independent of tumor response. Concordantly, epoetin alfa appeared to increase hemoglobin levels and decrease transfusion use. Patients responded across all tumor types. The results suggest that epoetin alfa effectively improves functional outcomes in patients with cancer who receive chemotherapy.

Aged↗
PubMed1997

Detection of circulating tumor cells in patients with Ewing's sarcoma and peripheral primitive neuroectodermal tumor.

PURPOSE: To determine the feasibility of detecting Ewing's sarcoma (ES) or peripheral primitive neuroectodermal tumor (PNET) through a reverse-transcriptase polymerase chain reaction (RT-PCR) of the t(11;22)(q24;q12) fusion transcript in blood and bone marrow samples from patients with these neoplasms. PATIENTS AND METHODS: Peripheral-blood (PB) and/or bone marrow aspirate (BM) samples were obtained from 28 patients with ES or PNET at initial presentation or at relapse. Patients were divided into two groups: newly diagnosed patients with nonmetastatic disease and those with metastatic/relapsed disease. RNA was extracted from fractionated BM and PB samples, and RT-PCR was performed for the EWS/HumFLI1 fusion mRNA was transcribed across the t(11;22) breakpoint. RESULTS: Among the 16 patients with nonmetastatic disease, three of 16 were RT-PCR positive for EWS/HumFLI1 RNA in BM and three of 10 were positive in PB. The total number of nonmetastatic patients who were positive in either PB or BM was four of 16 (25%). Among patients with metastatic/relapsed disease, two of six were positive in BM and five of 10 were positive in PB. The total fraction of patients with metastatic/relapsed disease that was positive in either BM or PB was six of 12 (50%). CONCLUSION: In this study, we show that it is possible to amplify the EWS/HumFLI1 RNA by RT-PCR from the BM and PB of a subset of patients with both nonmetastatic and metastatic ES or PNET, which implies that occult tumor cells are present at these sites. The true biologic and clinical meaning of this information is unknown. However, it does suggest a possible application of RT-PCR for the monitoring of residual disease in patients who are undergoing therapy for ES or PNET. This approach may permit early identification of patients who may benefit from alternative therapy or who may be spared possible overtreatment.

Chromosomes, Human, Pair 11↗
PubMed1996

Recombinant human stem cell factor (kit ligand) promotes human mast cell and melanocyte hyperplasia and functional activation in vivo.

Stem cell factor (SCF), also known as mast cell growth factor, kit ligand, and steel factor, is the ligand for the tyrosine kinase receptor (SCFR) that is encoded by the c-kit proto-oncogene. We analyzed the effects of recombinant human SCF (r-hSCF, 5-50 micrograms/kg/day, injected subcutaneously) on mast cells and melanocytes in a phase I study of 10 patients with advanced breast carcinoma. A wheal and flare reaction developed at each r-hSCF injection site; by electron microscopy, most dermal mast cells at these sites exhibited extensive, anaphylactic-type degranulation. A 14-d course of r-hSCF significantly increased dermal mast cell density at sites distant to those injected with the cytokine and also increased both urinary levels of the major histamine metabolite, methyl-histamine, and serum levels of mast cell alpha-tryptase. Five subjects developed areas of persistent hyperpigmentation at r-hSCF injection sites; by light microscopy, these sites exhibited markedly increased epidermal melanization and increased numbers of melanocytes. The demonstration that r-hSCF can promote both the hyperplasia and the functional activation of human mast cells and melanocytes in vivo has implications for our understanding of the role of endogenous SCF in health and disease. These findings also indicate that the interaction between SCF and its receptor represents a potential therapeutic target for regulating the numbers and functional activity of both mast cells and cutaneous melanocytes.

Anaphylaxis↗
PubMed1996

Chemotherapy and neutropenia.

Myelosuppression is the most common toxicity associated with the administration of dose-intensive cytotoxic chemotherapy. The basic understanding of neutrophil biology and the physiology of chemotherapy-induced neutropenia has advanced tremendously in the past 2 decades. Concordantly, the ability to reduce the morbidity associated with neutropenia has improved. Adjunctive cytokine and progenitor cell support of hematologic recovery after myelosuppressive therapy have proved to be models of translational research and have led to novel therapeutic initiatives for patients with cancer and hematologic malignancies. In this article, fundamental aspects of neutrophil production are discussed, and the clinical development of hematopoietic cytokines active on cells of the leukocyte lineages is presented.

Antineoplastic Agents↗
PubMed1996

Kinetics of peripheral blood mononuclear cell mobilization with chemotherapy and/or granulocyte-colony-stimulating factor: implications for yield of hematopoietic progenitor cell collections.

BACKGROUND: Peripheral blood progenitor cells (PBPCs) are commonly collected and used to reconstitute hematopoiesis after high-dose chemotherapy. However, strategies for optimal collection and assessment of leukapheresis components are not standardized. STUDY DESIGN AND METHODS: Hematopoietic progenitor cell assays were performed on 369 leukapheresis components collected from 95 patients who had received doxorubicin-based chemotherapy and/or granulocyte-colony-stimulating factor (G-CSF). Precollection patient hematologic values, leukapheresis collection values, component hematopoietic progenitor cell assays, and patient outcome measures were summarized. The kinetics of mononuclear cell (MNC) and PBPC mobilization were assessed among four patient groups. RESULTS: Patient group was a significant predictor of the peripheral blood MNC count on the day of collection (p<0.0001), and that value was a significant predictor of granulocyte-macrophage--colony-forming unit (CFU-GM) yield (p<0.0001). This relationship between the peripheral blood MNC count on the day of collection and CFU-GM yield differed according to patient group (p<0.0001). CFU-GM made up a larger fraction of peripheral blood MNCs collected from patients who received chemotherapy plus G-CSF than collected from those who received G-CSF alone. Moreover, the peripheral blood MNC count and the corresponding CFU-GM yield increased significantly on consecutive days of collection in patient groups receiving chemotherapy and G-CSF but were unchanged or decreased in patients receiving G-CSF alone. CONCLUSION: The relationship between peripheral blood MNC count and leukapheresis component CFU-GM yield differed significantly between patients who received chemotherapy and G-CSF and those who received G-CSF alone for the mobilization of PBPCs. Patient peripheral blood MNC count and component CFU-GM yield are useful for both assessing and suggesting revisions to PBPC mobilization and collection strategies.

Antineoplastic Agents↗
PubMed1996

Synovial sarcoma: prognostic significance of tumor size, margin of resection, and mitotic activity for survival.

PURPOSE: The present study serves to describe outcomes-based prognostic variables characteristic of synovial cell sarcoma. PATIENTS AND METHODS: An analysis was performed of a prospectively compiled data base of 48 consecutive patients with extremity and truncal synovial sarcomas seen between 1966 and 1994. RESULTS: No local recurrences were observed among 27 patients who presented with localized primary disease. Patients with synovial sarcoma less than 5 cm in size has a cancer-specific survival rate at 10 years of 100%, compared with a 10-year survival rate of 32% and 0% for those with sarcoma 5 to 10 cm and greater than 10 cm, respectively (P = .002). Patients with synovial sarcoma with less than 10 mitoses per 10 high-power fields (hpf) had a 10-year cancer-specific survival rate of 46%, compared with a 10-year survival rate of 14% for those with sarcomas with greater than 10 mitoses per hpf (P = .04). Patients with a clean margin of excision were found to have a 10-year cancer-specific survival rate of 43%, compared with 0% for those with microscopic positive margins (P = .03). Among 14 patients treated with neoadjuvant chemotherapy, seven (50%) had objective responses. CONCLUSION: Local control for patients with nonmetastatic disease was excellent. The overall cancer-specific survival rate for patients with localized synovial sarcoma was 34% at 10 years. Primary tumor size, margin of resection, and mean mitotic activity were prognostic factors for survival in synovial sarcoma. There was a high objective response rate to treatment with neoadjuvant chemotherapy; however, there was no detectable beneficial effects on survival in the subset of patients treated with chemotherapy versus nonrandomized patients who received no chemotherapy. Patients with synovial sarcoma > or = 5 cm in size, microscopic positive margins, and/or mean mitotic activity greater than 10 mitoses per 10 hpf should be targeted for new therapeutic studies.

Adult↗
PubMed1996

High-dose ifosfamide in the treatment of sarcomas of soft tissues and bone.

Ifosfamide is an alkylating agent with clinical activity in the treatment of sarcomas, and data support a dose-response relationship in this disease. Attaining a clinical response can be a significant end point in sarcomas because such a response may allow function-sparing surgery or improved surgical resection of bulky primary tumors. Studies have shown that higher response rates can be obtained in sarcomas using dose-intensified chemotherapy than with conventional-dose chemotherapy. Although the early data using high-dose ifosfamide in the treatment of sarcomas are promising, the median durations of response have been less than 1 year. The continuing advances in supportive care technology will facilitate the ability to conduct large-scale trials in sarcomas using dose-intensified chemotherapy. The aim of these trials should be to optimize the dosing and antineoplastic efficacy of ifosfamide as a single agent and in combination regimens.

Antineoplastic Agents, Alkylating↗
PubMed1995

Prognostic factors predictive of survival for truncal and retroperitoneal soft-tissue sarcoma.

OBJECTIVE: The authors identified prognostic factors relevant to clinical outcomes (especially survival) in truncal and retroperitoneal soft-tissue sarcoma. SUMMARY BACKGROUND DATA: These results can be used to optimize surgical management and select patients most likely to benefit from novel therapeutic strategies in future trials. METHODS: A retrospective analysis was performed of a prospectively compiled database of 183 consecutive patients with truncal and retroperitoneal sarcomas seen at the Brigham and Women's Hospital and the Dana Farber Cancer Institute between 1970 to 1994. RESULTS: For truncal sarcoma, multivariate analysis showed that high-grade histology was associated with an eightfold increased risk of death compared with low-grade histology (p = 0.001). In addition to grade, gross positive margin of resection (p = 0.001), microscopic positive margin (p = 0.023), and tumors greater than 5 cm in size (p = 0.018) were important independent prognostic factors for survival. In this series, postoperative radiation therapy for truncal sarcoma was associated with a 2.4-fold decreased risk of death compared with truncal sarcoma patients receiving no adjuvant radiation therapy, having adjusted for the other prognostic factors (p = 0.030). In contrast, for retroperitoneal sarcoma, multivariate analysis showed that high-grade and intermediate-grade histology were associated with a five- to sixfold increased risk of death compared with low-grade histology (p = 0.009). In addition to grade, gross positive margin of resection (p = 0.001) and microscopic positive margin (p = 0.004) were important independent prognostic factors for survival in retroperitoneal sarcoma. Patients who received either preoperative or postoperative chemotherapy for retroperitoneal sarcoma had a 4.6-fold (p = 0.002) and 3-fold (p = 0.010) increased risk of death, respectively, compared with patients receiving no adjuvant chemotherapy, having adjusted for the other prognostic factors. CONCLUSIONS: The histologic grade and the margin of resection are prognostic for survival in both truncal and retroperitoneal soft-tissue sarcoma. Tumor size was an independent prognostic factor for truncal sarcoma, but not for retroperitoneal sarcoma. Postoperative adjuvant radiation was beneficial to overall survival for truncal sarcoma. In this series of patients receiving a heterogeneous mixture of chemotherapeutic regimens-either as preoperative "neoadjuvant" therapy or as postoperative "adjuvant" therapy, there were no beneficial effects on survival compared with nonrandomized patients not receiving chemotherapy.

Adult↗
PubMed1995

Recombinant human granulocyte-macrophage colony-stimulating factor as an adjunct to conventional-dose ifosfamide-based chemotherapy for patients with advanced or relapsed germ cell tumors: a randomized trial.

PURPOSE: Ifosfamide-containing therapy with cisplatin plus either etoposide (VIP) or vinblastine (VeIP) can cure of patients with relapsed germ cell tumors (GCTs), but results in substantial myelotoxicity. This study sought to assess the impact of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on the severity of neutropenia and incidence of infectious complications in patients who receive ifosfamide-based chemotherapy for GCT. PATIENTS AND METHODS: One hundred and four assessable GCT patients from 20 centers were randomized to receive rhGM-CSF with either cycles 1 and 2 or cycles 3 and 4 of chemotherapy. Standard doses of VIP or VeIP were used. Efficacy data were analyzed using a parallel design for cycles 1 and 2 before the crossover. RESULTS: Fewer clinically relevant infections occurred in rhGM-CSF patients (13 of 55, 24%) versus observation patients (22 of 49, 45%) in cycle 1 (P = .01). Decreases were observed in infections during neutropenia (22% v 43%, P = .03), infections requiring intravenous antibiotics (20% v 43%, P = .01), and any infection irrespective of severity (29% v 55%, P = .01) in cycle 1. However, there were no significant differences among the treatment arms in cycle 2 in the proportion of clinically relevant infections (P = .23), infections associated with neutropenia (P = .11), infections requiring antibiotics (P = .22), or any infection (P = .65). rhGM-CSF was discontinued in 14% of cycles because of toxicity related to the growth factor. CONCLUSION: rhGM-CSF reduced the incidence of infections in the first cycle of chemotherapy, but no benefit beyond the initial chemotherapy cycle was evident. Based on the limited clinical impact and the high incidence of rhGM-CSF-related toxicity that required growth factor discontinuation, the routine administration of rhGM-CSF to prevent neutropenia and infection after ifosfamide-based chemotherapy for GCT patients is not recommended.

Adolescent↗
PubMed1995

Hematopoietic growth factors. Defining the appropriate clinical role in multimodality cancer therapy.

Laboratory investigations have begun to elucidate the regulatory molecules that control the processes of blood cell growth and differentiation. Recombinant human colony-stimulating factors are examples of biotechnology-produced molecules that have epitomized the translation of such basic scientific investigation into therapeutic advances. Small cell lung cancer, a malignancy that is overall highly sensitive to aggressive myelosuppressive chemotherapy at initial presentation, has been used as a clinical model in which the activity of human colony-stimulating factors has been tested. In this article, the clinical applications of hematopoietic growth factors are reviewed in brief. The appropriate clinical use of these agents may allow novel therapeutic strategies to be developed in a research setting. Similarly, these agents have the potential to improve supportive care and improve certain clinical outcomes in the non-research clinical care of patients. Issues of cost of treatment are raised by these agents, but the true clinical value of hematopoietic growth factors needs to be studied more rigorously, with emphasis on quality of life and redistribution of care costs outside of hospitals before definitive statements can be made.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Results of single-agent and combination chemotherapy for advanced soft tissue sarcomas. Implications for decision making in the clinic.

Cytotoxic chemotherapy remains the principal modality of treating advanced or unresectable sarcomas of soft tissue. Certain drugs, such as doxorubicin and ifosfamide, are able to induce clinically useful antitumor effects as single agents, and combination chemotherapy regimens have been tested based upon these results. This article summarizes the results of single agent and combination chemotherapy trials for soft tissue sarcomas.

Antineoplastic Agents↗
PubMed1994

Changes in Tc-99m radionuclide bone scan images and peripheralization of marrow hematopoietic activity associated with the administration of granulocyte colony stimulating factor as an adjunct to dose-intensified chemotherapy for breast cancer. A case report.

Granulocyte colony stimulating factor (G-CSF) is used clinically for chemotherapy-associated neutropenia. Very little is known about the manner in which pharmacologic dosing of G-CSF may affect radiologic studies in vivo. Dramatic changes on bone scan associated with the administration of G-CSF used to support dose-intensified combination chemotherapy in a patient with metastatic breast carcinoma are described. The scintigraphic findings were correlated histologically with increased hematopoietic activity in the bone marrow located in peripheral bones.

Adult↗
PubMed1994

The use of hematopoietic growth factors to support cytotoxic chemotherapy for patients with breast cancer.

The rationale for the uses of hematopoietic growth factors in the treatment of breast cancer is reviewed. The historical background of development of these novel therapeutic agents is also summarized as it pertains to patients undergoing myelosuppressive treatments. Important areas of controversy in the clinical uses of hematopoietic growth factors are identified, and future research directions in this field are discussed.

Antineoplastic Combined Chemotherapy Protocols↗