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Biomedical subjects

Shreyaskumar R Patel

Publications and source records attributed to Shreyaskumar R Patel.

At least 19 recordsLinked to original sources
PubMed2007

Chemotherapy response is an important predictor of local recurrence in Ewing sarcoma.

BACKGROUND: Local recurrence in Ewing sarcoma is associated with a poor prognosis. The purpose of the study was to determine the factors that predict local recurrence after surgical treatment of the primary tumor. METHODS: Between 1990 and 2001, 64 patients underwent surgical resection of Ewing sarcoma. Surgical margins were assessed histologically and radiologically. Response to preoperative chemotherapy was determined by detailed specimen mapping. Local recurrence-free survival (LRFS) was calculated by Kaplan-Meier analysis. Multivariate analysis was performed with the Cox proportional hazards model. RESULTS: A number of factors were found to be associated with local recurrence on univariate analysis. Patients with a good response to chemotherapy (> or = 90% tumor necrosis), had superior LRFS at 5 years (86% vs 51%, P = .015). Central site of disease was associated with an increased rate of recurrence. The LRFS at 5 years was 50% for the chest wall, 74% for pelvic/scapular, and 86% for extremity tumors (P = .083). Positive surgical margin was not a strong predictor of recurrence (P = .72). A critical analysis of minimal surgical margin based on preoperative magnetic resonance imaging (MRI) and computed tomography (CT) scans also failed to reveal an association between margin and local recurrence. In multivariate analysis, the 2 independent predictors of local recurrence were histological response to chemotherapy and central site of disease. CONCLUSION: Local recurrence after surgical resection is a complex phenomenon. An important predictive factor is the response to chemotherapy. In the current study, this seems to have the largest impact. Central site of disease may be a second independent predictive factor.

Adolescent↗
PubMed2007

Surgical resection of gastrointestinal stromal tumors after treatment with imatinib.

BACKGROUND: Surgical resection of gastrointestinal stromal tumors (GISTs) has been the most effective therapy for these rare tumors. Imatinib has been introduced as systemic therapy for locally advanced and metastatic GIST. In this study, the surgical resection rates and long-term outcomes of patients treated with preoperative imatinib for locally advanced primary, recurrent, or metastatic GISTs were evaluated. METHODS: Patients were retrospectively assessed for completeness of surgical resection and for disease-free and overall survival after resection. RESULTS: Forty-six patients underwent surgery after treatment with imatinib. Eleven were treated for locally advanced primary GISTs for a median of 11.9 months, followed by complete surgical resection. All eleven were alive at a median of 19.5 months, and ten were free of disease. Thirty-five patients were treated for recurrent or metastatic GIST. Of these, eleven underwent complete resection. Six of the eleven patients had recurrent disease at a median of 15.1 months. All eleven patients were alive at a median of 30.7 months. Patients with a partial radiographic tumor response to imatinib had significantly higher complete resection rates than patients with progressive disease (91% vs. 4%; P < .001). Of the 24 patients with incomplete resection, 18 initially responded to imatinib but were unable to undergo complete resection after they progressed before surgery. CONCLUSIONS: Preoperative imatinib can decrease tumor volume and is associated with complete surgical resection in locally advanced primary GISTs. Early surgical intervention should be considered for imatinib-responsive recurrent or metastatic GIST, since complete resection is rarely achieved once tumor progression occurs.

Adult↗
PubMed2006

Retroperitoneal soft tissue sarcoma: an analysis of radiation and surgical treatment.

PURPOSE: To evaluate the clinical outcomes of patients with localized retroperitoneal soft tissue sarcoma (STS) treated with complete surgical resection and radiation. METHODS AND MATERIALS: The medical records of 83 patients were reviewed retrospectively. Sixty patients presented with primary disease and the remaining 23 had recurrence after previous surgical resection. RESULTS: With a median follow-up of 47 months, the actuarial overall disease-specific survival (DSS), distant metastasis-free survival, and local control (LC) rates were 44%, 67%, and 40%, respectively. Of the 38 patients dying of disease, local disease progression was the sole site of recurrence for 16 patients and was a component of progression for another 11 patients. Multivariate analysis indicated that histologic grade was associated with the 5-year rates of DSS (low-grade, 92%; intermediate-grade, 51%; and high-grade, 41%, p = 0.006). Multivariate analysis also indicated an inferior 5-year LC rate for patients presenting with recurrent disease, positive or uncertain resection margins, and age greater than 65 years. The data did not suggest an improved local control with higher doses of external-beam radiation (EBRT) or with the specific use of intraoperative radiotherapy (IORT). Radiation-related complications (10% at 5 years) developed in 5 patients; all had received their EBRT postoperatively. CONCLUSIONS: Although preoperative radiation therapy and aggressive surgical resection is well tolerated in patients, local disease progression continues to be a significant component of disease death. In this small cohort of patients, the use of higher doses of EBRT or IORT did not result in clinically apparent improvements in outcomes.

Adult↗
PubMed2006

Correlation of immunophenotype with progression-free survival in patients with gastrointestinal stromal tumors treated with imatinib mesylate.

BACKGROUND: The therapy for gastrointestinal stromal tumor (GIST) has been revolutionized by imatinib mesylate (IM). It is unknown whether the levels of KIT expression or the presence of CD34, smooth muscle actin (SMA), desmin, or S-100 protein predicts patient outcome from IM therapy. In the current study, the prognostic effects for KIT and other proteins (CD34, SMA, desmin, S-100) were analyzed in a series of GISTs in which protein expression was evaluated by immunohistochemical analysis (IHC). METHODS: The cases of 106 patients with GIST who were uniformly treated with IM at the study institution between December 15, 2000, and January 13, 2002 were evaluated retrospectively. The association between KIT intensity, CD34, desmin, SMA, S-100 protein, and progression-free survival (PFS) was studied. Kaplan-Meier analysis and the Cox proportional hazards regression model were used for statistical analysis. RESULTS: The majority of tumors arose from the stomach (37%), small intestine (35%), and colorectum (14%). KIT expression as determined by IHC was categorized as weak (10%), intermediate (32%), or strong (58%). Patient tumors expressed CD34 (75%), SMA (56%), desmin (1%), and S-100 protein (32%). Patients whose GIST had weak, intermediate, or strong KIT expression were found to have an 18-month PFS rate of 80%, 84%, and 69%, respectively (P = .30). The presence or absence of CD34, SMA, desmin, or S-100 protein did not appear to correlate with PFS after IM. CONCLUSIONS: Patients with the appropriate clinical presentation and KIT-positive GIST tumors appear to benefit from IM independent of the level of KIT or the expression of CD34, SMA, desmin, or S-100 protein by IHC.

Adult↗
PubMed2005

Imatinib resistance in gastrointestinal stromal tumors.

Conventional chemotherapeutic drugs are ineffective in treatment of gastrointestinal stromal tumors (GISTs). Imatinib (STI571, Gleevec, Glivec; Novartis Pharmaceuticals, East Hanover, NJ), a selective inhibitor of KIT, ABL, BCR-ABL, PDGFRA, and PDGFRB, represents a new paradigm of targeted cancer therapy and has revolutionized the treatment of patients with chronic myelogenous leukemia and GISTs. Unfortunately, imatinib resistance has emerged. The reported mechanism of imatinib resistance in GISTs involves missense mutation in the kinase domain of KIT, including Thr670Ile, Tyr823Asp, and Val654Ala. The established mechanisms and potential mechanisms of imatinib resistance in GISTs, the imaging studies indicative of early development of imatinib resistance, and the management of imatinib-resistant GISTs are discussed.

Antineoplastic Agents↗
PubMed2005

Recent studies in novel therapy for metastatic sarcomas.

Many new chemotherapeutic agents and targeted therapies are being studied in the treatment of metastatic soft tissue sarcomas (STSs). This article reviews results of recent clinical studies of gemcitabine, docetaxel, paclitaxel, ecteinascidin, 9-nitrocamptothecin, and pegylated liposomal doxorubicin, in patients who have STSs. The use of targeted therapy in STSs is an exciting, constantly changing field. The activity of imatinib mesylate, SU11248, everolimus, and bortezomib are summarized.

Antineoplastic Agents↗
PubMed2004

Phase I trial of preoperative doxorubicin-based concurrent chemoradiation and surgical resection for localized extremity and body wall soft tissue sarcomas.

PURPOSE: The primary objective of this phase I trial was to define the maximum-tolerated dose of continuous-infusion doxorubicin administered with standard preoperative radiation for patients with localized, potentially resectable soft tissue sarcomas of the extremities or body wall. PATIENTS AND METHODS: Twenty-seven patients with radiographically resectable intermediate- or high-grade soft tissue sarcomas were treated. Preoperative external-beam radiation was administered in 25 2-Gy fractions (total dose, 50 Gy). Concurrent continuous-infusion doxorubicin was administered by an initial bolus (4 mg/m(2)) and subsequent 4-day continuous infusion (12.5, 15.0, 17.5, or 20.0 mg/m(2)/wk). Radiographic restaging was performed 4 to 7 weeks after chemoradiation, and patients with localized disease underwent surgical resection. RESULTS: Chemoradiation was completed as an outpatient procedure in 25 patients (93%). The maximum-tolerated dose of continuous-infusion doxorubicin combined with standard preoperative radiation was 17.5 mg/m(2)/wk; at this dose level, seven (30%) of 23 patients had grade 3 dermatologic toxicity. Macroscopically complete resection (R0 or R1) was performed in all 26 patients who underwent surgery. Among 22 patients who were treated with doxorubicin 17.5/mg/m(2)/wk with concurrent radiation and subsequent surgery, 11 patients (50%) had 90% or greater tumor necrosis, including two patients who had complete pathologic responses. CONCLUSION: Preoperative doxorubicin-based chemoradiation appears safe and feasible. The maximum-tolerated dose of continuous-infusion doxorubicin with standard preoperative radiation was 17.5 mg/m(2)/wk. Pathologic response rates with this regimen are encouraging.

Adolescent↗
PubMed2004

A phase II study of cisplatin, doxorubicin, and ifosfamide with peripheral blood stem cell support in patients with skeletal osteosarcoma and variant bone tumors with a poor prognosis.

BACKGROUND: The authors evaluated the efficacy and toxicity of cisplatin, ifosfamide, and doxorubicin with peripheral blood stem cell (PBSC) support in adult patients with osteosarcomas and variants with a poor prognosis. METHODS: Between December 1994 and January 2001, 37 patients (20 males and 17 females) with a median age of 38 years (range, 18-63 years) entered the study. Ten patients had pelvic osteosarcomas (OS), 6 had malignant fibrous histiocytomas, 5 had metastatic OS, and 16 had miscellaneous histologies. The authors used doxorubicin (60-75 mg/m(2)) and ifosfamide (10 g/m(2)) followed by granulocyte-colony-stimulating factor (G-CSF) (5 microg/kg twice per day) for mobilization of PBSC, collected at a median of 12 days (range, 10-14 days). Three cycles with cisplatin (120 mg/m(2)), ifosfamide (10 g/m(2)), and doxorubicin (75 mg/m(2)), given 28 days apart, were planned followed by PBSC (2-4 x 10(6) CD34-positive cells/kg) infusion plus G-CSF. RESULTS: Patients received a median of three cycles (range, one to three cycles) in addition to the mobilizing cycle. The median PBSC collection was 17.5 x 10(6)/kg (range, 13.2-90.8 x 10(6)/kg) with a median of 1 apheresis (range, 1-2 aphereses). Twenty-eight patients underwent surgery, 10 achieved 95-100% necrosis, and 4 achieved 90-94% necrosis. Six patients required early discontinuation of therapy due to toxicities, two patients developed progressive disease, and one patient was deemed unresectable. The median time to progression (TTP) and overall survival by Kaplan-Meier estimates for all 37 patients was 19 months and 49 months, respectively. CONCLUSIONS: The authors accomplished the objective of improving the rate of necrosis with intensification of preoperative therapy. However, TTP and survival rates remained poor. The toxicity profile of this regimen is prohibitive and alternative strategies need to be investigated.

Adolescent↗
PubMed2004

Interval between surgery and radiotherapy: effect on local control of soft tissue sarcoma.

PURPOSE: To evaluate the clinical significance of the interval between surgery and postoperative radiotherapy (RT) for patients with soft tissue sarcoma. METHODS AND MATERIALS: The records of 799 patients who underwent postoperative RT for soft tissue sarcoma between 1960 and 2000 were retrospectively reviewed. Univariate and multivariate analyses were used to evaluate the potential impact of the timing of postoperative RT on the rate of local control (LC). RESULTS: The actuarial overall LC rate was 79% at 10 years and 78% at 15 years. Univariate analysis indicated that the factors associated with an inferior 10-year LC rate were positive resection margins (p <0.0001); treatment for recurrent disease (p <0.0001); primary location in the head and neck or deep trunk (p <0.0001); age >64 years (p <0.0001); histopathologic subtype of malignant fibrous histiocytoma, neurogenic sarcoma, or epithelioid sarcoma (p = 0.01); tumor size >10 cm (p = 0.02); postoperative radiation dose <64 Gy (p = 0.03); and high histologic grade (p = 0.05). On multivariate analysis, all these factors remained statistically significant, except for high histologic grade and large size. A delay between surgery and the start of RT of >30 days was associated with a decreased 10-year LC rate, but this association was not statistically significant (76% vs. 83%, p = 0.07). The potential association between RT delay and inferior LC could be explained by an imbalance in the distribution of other prognostic factors. CONCLUSION: The interval between surgery and RT did not significantly impact the 10-year LC rate. These findings indicate that an RT delay should not be viewed as an independent adverse factor for LC and that treatment intensification may not be necessary for patients in whom a treatment delay has already occurred.

Adolescent↗
PubMed2003

A two-arm phase II study of temozolomide in patients with advanced gastrointestinal stromal tumors and other soft tissue sarcomas.

BACKGROUND: The authors conducted a two-arm Phase II study of temozolomide to determine its efficacy and toxicity in patients with soft tissue sarcomas (STSs) who had received, had refused, or were not eligible for standard chemotherapy with doxorubicin and ifosfamide (Arm 1) and in patients with gastrointestinal stromal tumors (GISTs; Arm 2). Patients with GIST were eligible regardless of prior therapy before imatinib was available. METHODS: Sixty patients were enrolled in the current study, 19 of whom had GISTs and 41 of whom had other STSs. The patients received temozolomide at a dose of 85 mg/m2 orally for 21 days followed by 7 days without treatment. Standard radiographic imaging after every two cycles was used to assess the treatment response. RESULTS: Of the 39 patients in Arm 1, there was 1 complete response and 1 partial response of 39 evaluable patients, for a total response rate of 5% (95% confidence interval, 0-12%). The responses lasted 7 months and 8 months, respectively. In Arm 2, there was no response in 17 patients. The disease was stable in 22% of the patients with GISTs and 33% of the patients with other STSs. The median overall survival time was 26.4 months in patients with GISTs and 11 months in patients with other STSs. The median time to disease progression was 2.3 months in patients with GISTs and 3.3 months in patients with other STSs. Grade 3 and Grade 4 adverse effects (according to National Cancer Institute Common Toxicity Criteria) were rare and included fatigue (eight patients), anemia (six patients), constipation (four patients), neutropenia (four patients), and thrombocytopenia (four patients). CONCLUSIONS: The data from the current study suggest that temozolomide is well tolerated but has only minimal efficacy and a limited role in the treatment of patients with STSs.

Administration, Oral↗
PubMed2003

Prognostic factors for disease-specific survival after first relapse of soft-tissue sarcoma: analysis of 402 patients with disease relapse after initial conservative surgery and radiotherapy.

PURPOSE: To document the prognostic factors for survival of patients with soft-tissue sarcoma sustaining a first relapse after definitive treatment. METHODS AND MATERIALS: The clinicopathologic features, relapse patterns, and disease-specific survival rates for 402 consecutive patients sustaining a first relapse of sarcoma after combined surgery and radiotherapy were retrospectively reviewed. Factors affecting disease-specific survival after relapse were evaluated with univariate and multivariate techniques. RESULTS: The median follow-up after relapse was 6.8 years. The overall disease-specific survival rate was 25%, 19%, and 16% at 5, 10, and 15 years, respectively, after the first relapse. The median survival duration was 21 months. Patients with an isolated local recurrence had a 5- and 10-year disease-specific survival rate of 48% and 46%, respectively, and those with an initial metastatic relapse had a disease-specific survival rate of 16% and 10%, respectively (p < 0.001). For isolated local recurrences, the independent determinants of survival were (favorable feature first) the primary tumor site (extremity and superficial trunk vs. head and neck and deep trunk); tumor grade (low and intermediate vs. high); time to recurrence (>12 vs. 5 cm). Although the development of subsequent metastasis was the major cause of death, a significant fraction of patients died of uncontrolled primary tumor. For patients presenting with metastasis as the first relapse, the time to metastasis was the major determinant of survival (>12 vs. < or =12 months). Long-term salvage was largely confined to patients who could and did undergo resection of relapsed disease, either local or metastatic. CONCLUSION: On the whole, patients whose sarcoma relapses fare poorly. However, select subgroups are potentially salvageable. Patients with an isolated local recurrence at sites other than the head and neck and deep trunk have a reasonable prospect for satisfactory outcome. Surgical resection of recurrences and metastases appears to play a major role in potential salvage.

Adolescent↗
PubMed2003

Phase I trial of preoperative concurrent doxorubicin and radiation therapy, surgical resection, and intraoperative electron-beam radiation therapy for patients with localized retroperitoneal sarcoma.

PURPOSE: The primary objective of this phase I trial was to define the maximum-tolerated dose of external-beam radiation with concurrent fixed-dose continuous-infusion doxorubicin followed by surgical resection and electron-beam intraoperative radiation therapy (EB-IORT) for patients with localized, potentially resectable retroperitoneal sarcomas (RPS). PATIENTS AND METHODS: Thirty-five patients with radiographically resectable primary or recurrent intermediate- or high-grade RPS were treated. Doxorubicin was administered each week for 4 or 5 weeks as an initial bolus (4 mg/m2) followed by a 4-day continuous infusion (4 mg/m2/d). Concurrent radiation therapy was administered in escalating doses of 18.0, 30.6, 36.0, 41.4, 46.8, or 50.4 Gy in 1.8-Gy fractions. Radiographic restaging was performed 4 to 8 weeks after chemoradiation, and patients with localized disease underwent surgical resection with EB-IORT (15 Gy). RESULTS: Chemoradiation was completed as outpatient therapy in 31 patients (89%); four patients required hospital admission during chemoradiation or in the postchemoradiation preoperative period. At the highest radiation dose of 50.4 Gy, two (18%) of 11 patients had grade 3 or 4 nausea. Twenty-nine patients (83%) underwent laparotomy; six patients had interval disease progression and did not undergo surgery. Grossly complete resection (R0 or R1) was performed in 26 (90%) of 29 patients who had surgery. EB-IORT was feasible and successfully administered to 22 patients who had R0 or R1 resections. CONCLUSION: Preoperative chemoradiation, surgical resection, and EB-IORT are feasible for patients with RPS. Preoperative external-beam radiation can be administered to a total dose of 50.4 Gy with continuous-infusion doxorubicin.

Adult↗
PubMed2003

Results of a 2-arm Phase II study of 9-nitrocamptothecin in patients with advanced soft-tissue sarcomas.

BACKGROUND: The authors conducted a 2-arm Phase II trial of 9-nitrocamptothecin (9-NC), an oral topoisomerase I inhibitor, to define response rates in patients with gastrointestinal (GI) leiomyosarcomas and other soft-tissue sarcomas (STS). METHODS: Patients were required to provide informed consent and have measurable disease, Zubrod performance status < or = 2, and adequate organ function. 9-NC was administered orally at 1.5 mg/m(2) per day x 5 days every week. Response evaluation was performed at 8 weeks, and those with stable or responding disease continued treatment until maximal response was achieved. A total of 56 patients (30 females and 26 males) with a median age of 55 years (range, 19-79 years) were enrolled on the study. Seventeen patients were enrolled on the GI leiomyosarcoma arm; only 1 minor response, lasting < 8 weeks in a patient with liver metastases, was noted, and so this arm was terminated. Thirty-nine patients were entered on the other STS arm. RESULTS: Three patients achieved a partial response (response rate, 8%) for durations of 4, 6, and 13 months, respectively. Fourteen patients had stable disease for a median of 4 months (range, 2-8 months). Two patients died of disease during the first 2 months. Four other patients required hospitalization for nausea, vomiting, and dehydration. Other toxicities included diarrhea (36 patients, 5 with Grade 3 toxicity); fatigue (42 patients, 11 with Grade 3 toxicity); anorexia (32 patients, 1 with Grade 3 toxicity); nausea (37 patients, 2 with Grade 3 toxicity); vomiting (24 patients, 3 with Grade 3 toxicity); neutropenia (14 patients, 5 with Grade 3 toxicity); and thrombocytopenia (16 patients, 5 with Grade 3 or 4 toxicity). CONCLUSIONS: 9-NC is well tolerated but inactive in GI leiomyosarcomas and has minimal activity in previously treated patients with STS.

Administration, Oral↗
PubMed2003

Preoperative vs. postoperative radiation therapy for soft tissue sarcoma: a retrospective comparative evaluation of disease outcome.

PURPOSE: Radiation (XRT) is a proven component in the treatment of soft tissue sarcoma. However, there is little evidence regarding the relative effectiveness of preoperative vs. postoperative XRT. This retrospective study addresses the relative effectiveness of disease control by these two treatment sequences. METHODS AND MATERIALS: A total of 517 patients (246 treated with postoperative XRT, and 271 treated with preoperative XRT) with nonmetastatic sarcoma were evaluated for disease outcome and late complications using univariate and multivariate techniques. RESULTS: With a median follow-up of 6 years, overall local control was 81% and 78% at 5 and 10 years, respectively. Although local control appeared superior with preoperative XRT (83% at 10 years) compared with postoperative XRT (72%), multivariate analysis revealed that this difference could be entirely explained by the unequal distribution of prognostic factors between the two groups, and there was no evidence that treatment sequence independently determined local control. There were no differences in nodal or metastatic relapse between the two treatments, and disease-specific survival was not significantly different. There was a slightly higher incidence of late XRT-related complications among those treated with postoperative XRT (10-year incidence of 9% vs. 5%, p = 0.03). CONCLUSIONS: This study found no evidence for differences in disease outcome attributable to the use of either pre- or postoperative XRT. There was a slight increase in long-term complications with postoperative XRT, likely due to the higher doses used in this sequence.

Adolescent↗
PubMed2003

Prognostic factors for patients with localized soft-tissue sarcoma treated with conservation surgery and radiation therapy: an analysis of 1225 patients.

BACKGROUND: Prognostic factors for patients with soft-tissue sarcoma who are treated with conservative surgery and radiation are documented poorly. METHODS: The clinicopathologic features and disease outcome for 1225 patients with localized sarcoma who were treated with conservative surgery and radiation were reviewed retrospectively. Actuarial univariate and multivariate statistical methods were used to determine significant prognostic factors for local control, metastatic recurrence, and disease specific survival. RESULTS: The median follow-up of surviving patients was 9.5 years. The respective local control rates at 5 years, 10 years, and 15 years were 83%, 80%, and 79%. Factors predictive of local recurrence were positive or uncertain resection margins; tumors located in the head and neck and the deep trunk; presentation with local recurrence; patient age > 64 years; malignant fibrous histiocytoma, neurogenic sarcoma. or epithelioid sarcoma histopathology; tumor measuring > 10 cm in greatest dimension; and high pathologic grade. Freedom from metastasis at 5 years, 10 years, and 15 years was 71%, 68%, and 66%, respectively. Factors that were predictive of metastatic recurrence were high tumor grade; large tumor size (> 5 cm); and leiomyosarcoma, rhabdomyosarcoma, synovial sarcoma, or epithelioid sarcoma. The respective disease specific survival rates at 5 years, 10 years, and 15 years were 73%, 68%, and 65%. Adverse factors for disease specific survival were high tumor grade; large tumor size (> 5 cm); tumors located in the head and neck and deep trunk; rhabdomyosarcoma, epithelioid sarcoma, or clear cell sarcoma; patient age > 64 years; and positive or uncertain resection margins. CONCLUSIONS: Soft-tissue sarcoma comprises a heterogeneous group of diseases. Prognostic factors for local recurrence, metastatic recurrence, lymph node recurrence, disease free survival, and disease specific survival are different, and optimal treatment strategies need to take this complexity into account.

Adolescent↗