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Shreyaskumar R Patel

Publications and source records attributed to Shreyaskumar R Patel.

31 records · Page 2Linked to original sources
PubMed2003

Surgical margins and reresection in the management of patients with soft tissue sarcoma using conservative surgery and radiation therapy.

BACKGROUND: Patients with localized soft tissue sarcoma (STS) who present to specialist centers after undergoing apparent macroscopic total resection often have a significant incidence of residual tumor and may benefit from reresection of the tumor bed. The potential benefits of such reresection have not been documented adequately. METHODS: The clinicopathologic features and disease outcome for 666 consecutive patients with localized STS who presented after undergoing apparent macroscopic total tumor resection were analyzed to elucidate the relative merits of reresection. Actuarial univariate and multivariate methods were used to compare disease outcome of patients who presented with positive or uncertain microscopic resection margins according to whether they underwent reresection. All patients received adjuvant radiation therapy. RESULTS: Two hundred and ninety-five patients underwent reresection of their tumor bed, and residual tumor was found in 136 patients (46%), including macroscopic tumor in 73 patients (28%). Final resection margins among patients who underwent reresection were negative in 257 patients (87%), positive in 35 patients (12%), and uncertain in 3 patients (1%). Patients who did not undergo reresection had final margins that were negative in 117 patients (32%), positive in 47 patients (13%), and uncertain in 207 patients (56%). Local control rates at 5 years, 10 years, and 15 years for patients who underwent reresection were 85%, 85%, and 82%, respectively; for patients who did not undergo reresection, the respective local control rates were 78%, 73%, and 73% (P = 0.03). Reresection remained a significant determinant of local control when other prognostic factors were incorporated into a multivariate proportional hazards regression analysis. A similar beneficial effect of reresection was found for metastasis free survival and disease specific survival. CONCLUSIONS: Patients with localized STS who were referred to a specialist center after undergoing apparent macroscopic total resection of their tumor had a high incidence of residual tumor in their tumor bed and benefited from undergoing reresection, even if radiation was administered routinely.

Adolescent↗
PubMed2003

Is there a role for surgery in patients with "unresectable" cKIT+ gastrointestinal stromal tumors treated with imatinib mesylate?

BACKGROUND: Imatinib mesylate (Gleevec) is being studied as adjuvant chemotherapy for the treatment of cKIT+ gastrointestinal stromal tumors (GISTs). Early reports using Gleevec for the treatment of unresectable GISTs have shown 50% to 60% partial response rates based on radiographic evaluation alone. No study has yet correlated radiographic response with pathologic findings. This retrospective review of patients with cKIT+ GISTs who received Gleevec prior to surgical resection examines the pathologic response to therapy and the feasibility of surgical resection after treatment. METHODS: Patients with cKIT+ GISTs were identified from the institutional sarcoma database. Patients were included if they had pathologic confirmation of cKIT mutation and therapy with Gleevec. The pretreatment and preoperative radiographs, surgeons' operative notes, and pathology reports were reviewed for documentation of the extent of disease. RESULTS: Between January 2001 and Octorber 2002, 126 patients with unresectable cKIT + GISTs treated with Gleevec were identified. Of these 126 patients, 17 have subsequently undergone surgical resection after a median of 10 months (range 2 to 16) of treatment with Gleevec. Based on computed tomographic (CT) scanning, 1 (6%) patient had evidence of a complete tumor response, 12 (70%) patients had a partial response, 3 (24%) patients had stable disease, and 1 (6%) patient had progressive disease. Posttreatment/preoperative CT imaging documented an overall response rate of 76%. The pathologic review of the operative specimens showed that 2 (12%) patients had a complete response to therapy, 11 (65%) had a partial response to therapy, 3 (18%) patients had no evidence of treatment effect on the excised tumor, 1 patient had progressive disease. Sixteen patients (94%) underwent complete surgical resection of disease, including 3 patients with no pathologic evidence of response to therapy. One patient had progression of disease and was unresectable at surgical exploration. CONCLUSIONS: This series is the first to present pathologic data after the treatment of cKIT+ GISTs with Gleevec. In this series, the majority of responses were limited to partial responses, indicating that surgical resection remains a vital component of the treatment plan for patients with cKIT+ GISTs. This series is consistent with previous reports indicating that complete responses are extremely rare in response to treatment with Gleevec. Patients with advanced disease may benefit from a course of neoadjuvant therapy with Gleevec followed by resection, even when there is evidence of multifocal disease. A prospective evaluation of neoadjuvant Gleevec therapy for advanced cKIT+ GISTs is warranted.

Adult↗
PubMed2003

The follow-up of adult soft-tissue sarcomas.

Soft-tissue sarcomas are a rare and heterogeneous group of diseases with variable biology and pattern of metastases. These characteristics make it challenging to conduct large, randomized studies that could be used to generate evidence-based guidelines for unique subsets. Much of the data summarized here therefore represents standard practice based on the consensus of a group of experienced specialists and retrospective analysis of large databases. A surveillance guideline should be based on known prognostic factors, outcomes in individual subsets, and patterns of recurrence. It has to be practical and relatively cost-effective. The major goals of such an algorithm for soft-tissue sarcomas would be early identification of potentially curable recurrences, identification of therapy-related complications, and patient reassurance.

Adult↗
PubMed2003

Recent advances in systemic therapy of soft tissue sarcomas.

Improvements in surgical techniques, for example reconstructive surgery; and radiation therapy techniques, such as intensity-modulated radiotherapy; have made some impact on the functional outcomes of sarcomas with a local biology. Effective local control can be achieved with effective function in the vast majority of patients. The problem of distant metastases, however, continues to plague a large group of patients with this disease. Recent advances in the systemic therapy of sarcomas is highlighted by the rapid development and approval of the molecularly targeted therapy imatinib (Gleevec) for advanced gastrointestinal stromal tumors. Several other agents have been, or are being studied with far less rewarding results. Among these, the more encouraging examples include the nucleoside analog gemcitabine (Gemzar) and gemticibine/docetaxel (Taxotere) in combination, which display some selective activity in sarcomas of gynecologic origin. The marine compound ecteinascidin (ET-743) has been studied in two different schedules (24 and 3 h infusions), demonstrating biological activity worthy of further investigation. Identification of new agents with activity in this diverse group of diseases is extremely important. Identification of specific targets responsible for tumorigenesis and effective inhibition of these targets holds the most promise for future improvement in cure rates. However, until such time, it is equally important to emphasize clinical research attempting to further optimize the use of the standard chemotherapeutic agents, with growth-factor support in appropriately selected patients.

Antineoplastic Agents↗
PubMed2002

Radiographic response to neoadjuvant chemotherapy is a predictor of local control and survival in soft tissue sarcomas.

BACKGROUND: Downstaging of large soft tissue sarcomas can be accomplished by the use of neoadjuvant chemotherapy (NeoCT). The authors tested the hypothesis that radiographic response to NeoCT predicts improved local control and survival. METHODS: The authors reviewed the medical records of 65 patients with Stage II or III soft tissue sarcoma (42 extremity, 23 retroperitoneal) who were treated with doxorubicin or ifosfamide-based NeoCT from January 1991 to December 1996. Radiographic response and impact on surgical therapy were determined retrospectively by comparing imaging studies obtained before and after chemotherapy. RESULTS: The radiographic responses observed were partial response (PR; 22 patients [34%]); minor response (MR; 6 patients [9%]); stable disease (20 patients [31%]); and progressive disease (17 patients [26%]). Downstaging sufficient to decrease the scope of the operation occurred in 13% of the patients, 78% had no change, and 9% had disease progression sufficient to increase the scope of the operation. Patients having any radiographic response (PR or MR) had a higher margin-negative resection rate, a better local recurrence-free survival rate, and a better overall survival rate than did nonresponders. CONCLUSIONS: The NeoCT regimens used in this study resulted in tumor shrinkage sufficient to impact surgical therapy in a few patients. However, radiographic response predicted improved local control and overall survival rate.

Adolescent↗
PubMed2002

Adult rhabdomyosarcoma: outcome following multimodality treatment.

BACKGROUND: Childhood rhabdomyosarcoma (RMS) has a relatively good prognosis. Outcome for adults with this disease is poorly documented due to its rarity. METHODS: The clinicopathologic features, treatment methods, and disease outcome were reviewed retrospectively for 82 adults with locoregional RMS treated between 1960 and 1998. Patients with distant metastasis at diagnosis were excluded. Actuarial univariate and multivariate statistical methods were used to evaluate outcome. RESULTS: Patient ages ranged from 17 to 84 years (median, 27 years). Histologic subtypes were embryonal (34%), pleomorphic (43%), and alveolar (23%). Anatomic sites of origin were head and neck (52%), trunk (26%), and extremity (7%). Tumor size was 5 cm or smaller in 51% of patients. Regional lymph node metastasis was present in 33% of patients at presentation. Treatment consisted of radiation alone in 11%, radiation and surgery in 18%, radiation and chemotherapy in 34%, and all three modalities in 37%. With a median follow-up of 10.5 years, the 10-year actuarial disease-free and overall survival rates were 41% and 40%, respectively. The 10-year actuarial local, lymph node, and metastatic control rates were 75%, 82%, and 53%, respectively. The major determinant of metastatic control and survival was primary tumor size (< or = 5 vs. > 5 cm). Local control was satisfactory (10-year rate of 87%) for sites other than parameningeal (50% at 10 years). Patients whose disease responded to chemotherapy had a significantly better metastasis free period (72% at 10 years) than those whose disease failed to respond (19% at 10 years). CONCLUSIONS: Adult RMS is a highly malignant tumor with a significant incidence of metastatic recurrence. Continuing investigation of new and potentially more effective chemotherapy is crucial. Local control is satisfactory for sites other than parameningeal where new radiation technologies such as intensity-modulated therapy may be necessary to safely deliver adequate doses.

Adolescent↗
PubMed2002

Extraosseous osteosarcoma: response to treatment and long-term outcome.

PURPOSE: To evaluate the clinicopathologic features of extraosseous osteosarcoma (EOO), a rare soft tissue form of osteosarcoma, and to examine its response to multimodality therapy. PATIENTS AND METHODS: The medical records of all patients with EOO evaluated at The University of Texas M.D. Anderson Cancer Center between 1960 and 1999 were reviewed for clinicopathologic factors, treatment, and outcome. RESULTS: Sixty consecutive patients with EOO were identified, including 38 patients with localized (American Joint Committee on Cancer stages I to III) disease. The majority of patients presented with T2 tumors (n = 35, 58%), and 90% of tumors were located beneath the investing fascia. Twenty-seven patients with measurable and assessable disease were treated with doxorubicin-based chemotherapy (median doxorubicin starting dose, 75 mg/m(2); median number of cycles, four). The overall response rate was 19%, with two complete and three partial responses; one (6%) of 18 doxorubicin-treated patients who underwent subsequent surgery had a pathologic complete response. For the subset of 30 patients with localized disease treated at M.D. Anderson, the 5-year actuarial local recurrence-free, distant recurrence-free, event-free, and disease-specific survival rates were 82% (95% confidence interval [CI], 70% to 98%), 64% (95% CI, 43% to 93%), 47% (95% CI, 30% to 70%), and 46% (95% CI, 26% to 80%), respectively. CONCLUSION: EOO should be considered clinically and therapeutically distinct from osseous osteosarcoma. Radiographic response rates and pathologic complete response rates to doxorubicin-based systemic therapy are low.

Adolescent↗
PubMed2002

Cost-effectiveness of staging computed tomography of the chest in patients with T2 soft tissue sarcomas.

BACKGROUND: Published practice guidelines recommend routine chest computed tomography (CT) scanning as part of the staging evaluation for patients with T2 soft tissue sarcomas (STS), although there is no direct evidence to support this practice. The objective of this study was to determine the yield and cost-effectiveness of routine versus selective chest CT scanning for the staging of patients with T2 STS and to identify any subgroups for whom a more selective approach to chest CT scanning could be considered. METHODS: Six hundred consecutive patients with primary, nonthoracic, T2 (> 5 cm) STS underwent both chest X-ray (CXR) and chest CT scanning to evaluate the presence of pulmonary metastatic disease (M1). The authors constructed a decision tree that modeled the outcomes of diagnostic testing for two hypothetical diagnostic strategies: 1) routine chest CT (rCT) or 2) CXR and selective chest CT (sCT). The yield and cost of each strategy were determined; the incremental cost-effectiveness ratio (ICER) was calculated as the cost per additional patient with pulmonary metastases identified by rCT versus sCT. RESULTS: The yield of rCT was higher than that of sCT (M1 disease identified in 19.2% vs. 16.0% of patients, respectively), but rCT was more costly ($1301 vs. $418 per patient, respectively). The ICER of rCT compared with sCT was $27,594 per patient identified with pulmonary metastasis. The expected yields, costs, and ICERs of the diagnostic strategies varied across patient subgroups based on grade, anatomic site, and tumor size. CONCLUSIONS: For patients with T2 STS, rCT was most cost-effective in patients with high-grade lesions or extremity lesions. The findings of this study do not support the routine use of chest CT scanning in all patients with T2 STS.

Adolescent↗
PubMed2002

Preoperative chemoradiation treatment strategies for localized sarcoma.

BACKGROUND: Over the past 2 decades, there has been increasing interest in chemoradiation treatment strategies for patients with soft tissue sarcomas. Investigators have evaluated: (1) the optimal route for chemotherapy administration (intra-arterial vs. intravenous); (2) the possible advantages of protracted infusion of the radiosensitizer versus brief infusion; (3) the efficacy and toxicity of various intravenous and oral radiation sensitizers; and (4) the efficacy of sequential versus concurrent combined modality treatment. METHODS: The English-language literature addressing chemoradiation for localized and locally advanced extremity and retroperitoneal sarcomas was reviewed. RESULTS: All studies have been pilot, phase I, or phase II designs. The most commonly used radiosensitizer for concurrent chemoradiation has been doxorubicin, administered intravenously in most recent reports. In the studies that have included assessment of recurrence-free survival, preoperative chemoradiation combined with surgery has resulted in favorable local control rates, often in excess of 90% for patients with localized and locally advanced extremity sarcomas. CONCLUSIONS: The toxicities and recurrence-free outcome with chemoradiation plus surgery for soft tissue sarcoma still need to be compared to these with surgery and pre- or postoperative radiation. However, the generally favorable local control rates reported for chemoradiation justify continued investigation of preoperative chemoradiation strategies for localized sarcoma.

Antineoplastic Agents↗
PubMed2002

Systemic therapy for advanced soft-tissue sarcomas.

The field of oncology is experiencing a paradigm shift from broad-spectrum cytotoxic therapies to more specific molecularly based targeted therapies. The activity of imatinib mesylate in chronic myelogenous leukemia and gastrointestinal stromal tumors (GIST) has reinforced our faith in translational research and its potential impact on the cure of cancer and improvement in quality of life for patients. This breakthrough has been particularly exciting for the field of sarcoma and for patients with advanced GIST, for whom no other effective therapy was available. Unfortunately, as is becoming increasingly clear, cancer is a very complex problem with multiple mechanisms and pathways that function either independently or interdependently enabling cell survival. We are therefore far away from having solved the problem. Attempts at refining the currently available therapeutic armamentarium to maximize the therapeutic index (dose intensification with growth factor support) must continue in parallel with laboratory-based research identifying critical targets to be inhibited or blocked. Identification of new agents with some activity, such as gemcitabine and ecteinascidin (ET-743), is also of paramount importance.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Gastrointestinal stromal tumors: rationale for surgical adjuvant trials with imatinib.

Gastrointestinal stromal tumors (GISTs) constitute the majority of mesenchymal tumors involving the gastrointestinal tract. Over the past decade, it has been recognized that these tumors have distinctive immunohistochemical and genetic features. The expression of c-Kit (CD117), a transmembrane growth factor receptor, has emerged as an important defining feature of GISTs, and the pathogenesis of these tumors may be related to c-Kit mutations. Promising preclinical results have provided the driving force for the rapid clinical development of imatinib mesylate, a selective tyrosine kinase inhibitor of c-Kit. This novel molecularly targeted therapy has produced impressive clinical responses in a large proportion of patients with advanced GISTs and is under study as an adjuvant therapy in patients with localized resectable GISTs.

Animals↗
PubMed2002

Developing therapeutic pharmaceuticals for the treatment of soft-tissue sarcomas.

Recent progress in the therapy of sarcomas is highlighted by the rapid development and approval of the molecularly targeted therapy imatinib mesylate (STI571, Gleevec) for advanced gastrointestinal stromal tumours. Several other agents are in various stages of clinical development with far less rewarding results based on the preliminary data available. Amongst these, the encouraging ones include the nucleoside analogue gemcitabine and gemcitabine/docetaxel combination with some selective activity in sarcomas of gynaecological origin. The marine compound ecteinascidin-743 (ET743) has been studied in two different schedules (24-h and 3-h infusions) with some interesting biological activity worthy of further investigation. Identification of new agents with activity in this diverse group of diseases is extremely important.

Antineoplastic Agents↗