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M P Mehta

Publications and source records attributed to M P Mehta.

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

Stereotactic radiosurgery for brain metastases.

Worldwide, approximately 100,000 patients have undergone stereotactic radiosurgery for a variety of intracranial lesions, of which brain metastases represent the most common treatment indication. This article summarizes the major issues surrounding the management of brain metastases, and also analyzes 21 independent reports of Gamma Knife- or linear accelerator-based radiosurgery, representing over 1,700 patients and more than 2,700 lesions. Variable reporting in the studies precludes a definitive, rigorous analysis, but the composite data reveal an average local control rate of 83% and median survival of 9.6 months, both of which are comparable to results in recent surgical reports. The most important prognostic factors for survival appear to be fewer than three lesions, controlled extracranial disease, and Karnofsky performance score (KPS). The exact impact of dose has not been clarified, but a dose-response relationship, especially for > or = 18 Gy, is emerging. The role of whole-brain radiotherapy remains unresolved. It may enhance local control but does not convincingly improve survival and, in some series, is associated with an increased risk of late complications. Chronic steroid dependence and increased intracranial edema do not appear to be common problems. This is an opportune time for the completion of ongoing randomized trials to validate these observations.

Brain Neoplasms↗
PubMed1998

Evaluation of Internet-based oncologic teaching for medical students.

BACKGROUND: Electronic tools with substantial educational applications are now widely available. METHODS: In a prospective, randomized study, the value of Web-based educational tools for teaching second-year medical students was evaluated. The 35-hour, image-intensive multifaculty neoplasia course was selected for the experiment, with 103 students assigned to the control group (C) and 61 to the experimental group (E). Representative password-controlled multimedia course modules, accessible via the Internet, were developed. The E cohort was exposed to both classroom and Web-aided materials, whereas the C group had access to the Web modules only after the experiment was concluded (but before the final examination). Pre- and post-exposure questionnaires assessed computer knowledge, familiarity with the Internet, availability of computer access, and the value of Web-based education for both cohorts. Additionally, pre-and post-exposure tests were administered to both cohorts based on educational materials presented in the Web modules. RESULTS: The overall participation rate was 64% (E = 69%; C = 60%). The post-test showed no major performance difference between the two groups. The questionnaires revealed that: less than 1% of the students had not accessed the Internet previously; less than 5% had not used the Internet for medical education before; 34% felt that computer resources on campus were inadequate; and over 75% found Web-based education to be an important additional educational resource. The major negative aspect was the slow pace of data transfer for modem-based home access. Only 1% of students felt that Web-based education could completely replace traditional teaching. CONCLUSION: The potential for incorporating Web-based education in the medical curriculum is considerable.

Computer Literacy↗
PubMed1998

Phase II trial of hyperfractionated accelerated radiation therapy for nonresectable non-small-cell lung cancer: results of Eastern Cooperative Oncology Group 4593.

PURPOSE: To assess the feasibility, toxicity, and efficacy of hyperfractionated accelerated radiation therapy (HART) for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Thirty patients from six institutions with stage IIIA or IIIB NSCLC were enrolled between November 1993 and August 1995. Radiation therapy (total dose, 57.6 Gy in 36 fractions) was delivered over 15 days with the use of three daily fractions with a 4-hour interval between fractions and an 8-hour interval between on-cord fields. Patients were not treated on weekends. RESULTS: Twenty-eight patients (93%) completed radiation therapy. Treatment-related toxicities of grade 3 or greater included esophagitis in six patients and grade 3 skin reaction in three patients. The overall objective response rate was 54%, and the response rate within the radiation field was 64%. With a minimum follow-up of 19 months in surviving patients, the median survival and 1-year survival rate are 13 months and 57%, respectively. The median relapse-free survival and 1-year relapse-free survival rate are 7 months and 23%, respectively. No transverse myelitis or late toxicities of grade 4 or greater have been observed. CONCLUSION: HART, delivered to a total dose of 57.6 Gy over 15 total days, is practical and well tolerated. Survival appears similar to that seen with modern combined modality regimens. A phase III trial is under way.

Aged↗
PubMed1998

Phase I study of paclitaxel in patients with recurrent malignant glioma: a North American Brain Tumor Consortium report.

PURPOSE: To determine the maximum-tolerated dose (MTD) of paclitaxel administered as a 3-hour infusion in patients with recurrent malignant glioma. PATIENTS AND METHODS: Patients were stratified by starting dose of paclitaxel and concurrent anticonvulsant (AC) use and were treated in cohorts of three patients. The starting dose was 240 mg/m2 administered intravenously with escalations of 30 mg/m2 until the MTD was established. Pharmacokinetic data were obtained for each patient for the first infusion. Tumor response was assessed at 6-week intervals and treatment was continued until documented tumor progression, unacceptable toxicity, or a total of 12 paclitaxel infusions. RESULTS: From April 1995 to December 1996, 34 patients were treated; 27 patients in the AC group and seven patients in the non-AC group. The MTD for patients who received ACs was established at 360 mg/m2 and the dose-limiting toxicity (DLT) was central neurotoxicity, characterized as transient encephalopathy and seizures. In contrast, the MTD for patients who did not receive ACs was 240 mg/m2, and myelosuppression, gastrointestinal toxicity, and fatigue were the DLTs. Pharmacokinetic data confirmed that the plasma drug levels and clearance rates were similar for patients in both groups at the respective dose levels that produced DLTs. CONCLUSION: The pharmacokinetics of paclitaxel are altered by ACs, and significantly larger doses of the drug can be administered to patients with brain tumors on AC therapy. The toxicity profile is different for patients on AC therapy treated at these higher doses. A phase II study has been initiated that uses a dose of 330 mg/m2 for patients on AC therapy and 210 mg/m2 for patients not on AC therapy.

Adult↗
PubMed1998

Protection of normal tissues from the cytotoxic effects of radiation therapy: focus on amifostine.

Evidence for the use of amifostine (Ethyol, ALZA Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA) as a radioprotectant has been gathered in a number of clinical trials conducted over the past decade. This report briefly reviews those trials, as well as highlights results of a recent phase II trial conducted to evaluate the efficacy of daily amifostine administration in reducing the incidence of radiation-induced esophagitis in patients with stage III non-small cell lung cancer. Of 25 patients evaluated, none experienced grade 3 or 4 esophagitis or dyspnea. No patients required discontinuation of therapy due to amifostine-induced hypotension. There was a 60% objective response rate and 1-, 2-, and 3-year survival rates were 55%, 23%, and 23%, respectively. Thus, amifostine administration reduced radiation-induced toxicities without reducing antitumor efficacy.

Amifostine↗
PubMed1997

The effect of M-stage on patterns of failure in posterior fossa primitive neuroectodermal tumors treated on CCG-921: a phase III study in a high-risk patient population.

PURPOSE: To analyze patterns of failure in patients (pts) with high-risk posterior fossa primitive neuroectodermal tumors (PF-PNETs) treated with combined modality therapy on a large, randomized multiinstitutional study. METHODS AND MATERIALS: One hundred eighty-eight prospectively staged pts with PF-PNET confirmed by central pathology review, with high-risk features, were treated on Children's Cancer Group Study 921 (CCG-921), comparing two chemoradiotherapy regimens. Patterns of initial sites of failure were analyzed, specifically evaluating the impact of Chang M-stage. RESULTS: Progression-free survival (PFS) correlated with the presence or absence of metastatic disease (p < 0.001), with 5-year PFS of 68 +/- 5.8% for M0 vs. 43 +/- 6.8% for M+ pts. The cumulative incidence functions (CIF) of recurrence were different (p = 0.005) and at 5 years were 29 +/- 4.7% for M0 pts and 48 +/- 5.5% for M+ pts. Involvement of the PF at time of initial failure as measured by CIF correlated with M-stage (p = 0.047) and occurred in 18 +/- 3.9% of M0 pts and 8 +/- 2.9% of M+ pts overall; PF as the only site of relapse also correlated with M-stage (p = 0.019) and was seen in 6 +/- 2.5 and 0% of M0 and M+ pts, respectively, at 5 years. Relapse in the spine and/or cerebrospinal fluid (CSF) at initial recurrence was correlated with M-stage (p < 0.002), with 5-year cumulative incidences of 14 +/- 3.7%, 26 +/- 8.2%, 40 +/- 15%, and 40 +/- 7.7% for M0, M1, M2, and M3 pts, respectively. Isolated spine/CSF recurrence correlated with M-stage (p = 0.034) and occurred in 2 +/- 1.5% of M0 and 9 +/- 3.2% of M+ pts by 5 years. The median time to relapse for pts who failed was 1.2 years (range 0.2-5.3). Ninety percent of all relapses occurred by 3 years. CONCLUSIONS: Original sites of disease are at the highest risk for relapse, but the entire neuraxis remains at significant risk, despite combined-modality treatment. M-Stage was prognostic for spine/CSF relapse as well as PFS and may be an important tool in guiding therapy. A more aggressive approach to local control in the neuraxis is warranted, especially in M+ patients.

Adolescent↗
PubMed1997

Effect of amifostine on toxicities associated with sequential chemotherapy and radiation therapy for unresectable non-small-cell lung cancer: results of a phase II trial.

PURPOSE: To determine the effect of amifostine on the safety and efficacy of induction chemotherapy with high-dose cisplatin and vinblastine followed by large-field thoracic irradiation to 60 Gy in patients with stage IIIA or IIIB non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Twenty-six patients with unresectable stage IIIA or IIIB NSCLC were entered onto the study between May 1991 and November 1994. Patients received amifostine (740 or 910 mg/m2) followed by cisplatin (120 mg/m2) on days 1 and 29. Vinblastine (5 mg/m2) was given weekly for 5 weeks with no amifostine pretreatment. Following chemotherapy, patients received amifostine (340 mg/m2 4 days a week for 5 weeks, or 200 mg/m2 5 days a week for 6 weeks) 15 minutes before definitive thoracic radiation therapy to a total dose of 60 Gy in 6 weeks. RESULTS: Twenty-five patients were assessable for response and survival. The objective response rate was 60%. One-, 2-, and 3-year survival rates were 55%, 23%, and 23%. There was no grade 3 or greater renal toxicity during chemotherapy or grade 3 or greater esophagitis during radiation therapy. Neutropenia (secondary to vinblastine use) was the only grade 4 toxicity. There were no treatment-related deaths. CONCLUSION: Amifostine can be administered safely with high-dose cisplatin, vinblastine, and radiation therapy for NSCLC. The response rate and survival data provide no evidence that amifostine impairs response to treatment. Amifostine appears to reduce cisplatin-related nephrotoxicity and radiation-induced esophagitis.

Adult↗
PubMed1996

A multiinstitutional outcome and prognostic factor analysis of radiosurgery for resectable single brain metastasis.

PURPOSE: Recent randomized trials of selected patients with single brain metastasis comparing resection followed by whole-brain radiotherapy (WBRT) to WBRT alone have shown a statistically significant survival advantage for surgery and WBRT. A multiinstitutional retrospective study was performed, which identified comparable patients who were treated with stereotactic radiosurgery (RS) and WBRT. METHODS AND MATERIALS: The RS databases of four institutions were reviewed to identify patients who met the following criteria: single-brain metastasis; no prior cranial surgery or WBRT; age > 18 years; surgically resectable lesion; Karnofsky Performance Status (KPS) > or = 70 at time of RS; nonradiosensitive histology. One hundred twenty-two patients were identified who met these criteria. Patients were categorized by: (a) status of the primary, (b) status of non-CNS metastasis, (c) age, (d) baseline KPS (from 70-100), (e) histology, (f) time from diagnosis of primary to the detection of the brain metastasis, (g) gender, and (h) tumor volume. RS was performed with a linear accelerator based technique (peripheral dose range was 10-27 Gy, median was 17 Gy). WBRT was performed in all but five patients who refused WBRT (dose range was 25-40 Gy, median was 37.5 Gy). RESULTS: The median follow-up for all patients was 123 weeks. The overall local control rate (defined as lack of progression in the RS volume) was 86%. Intracranial recurrence outside of the RS volume was seen in 27 patients (22%). The actuarial median survival from date of RS is 56 weeks, and the 1-year and 2-year actuarial survival rates are 53% and 30%. The median duration of functional independence (sustained KPS > or = 70) is 44 weeks. Nineteen of 77 deaths were attributed to CNS progression (25% of all deaths). Multivariate analysis revealed the following factors to be statistically significant predictors of survival: baseline KPS (p < .0001) and absence of other sites of metastasis (p = 0.008). CONCLUSION: The RS in conjunction with WBRT for single brain metastasis can produce substantial functional survival, especially in patients with good performance status and without extracranial metastasis. These results are comparable to recent randomized trials of resection and WBRT. The advantages of RS over surgery in terms of cost, hospitalization, morbidity, and wider applicability strongly suggest that a randomized trial to compare RS with surgery is warranted.

Adult↗
PubMed1996

The potential of topoisomerase I inhibitors in the treatment of CNS malignancies: report of a synergistic effect between topotecan and radiation.

Despite innovations in imaging, surgery, and radiation therapy, local failure remains the principle clinical problem in most CNS malignancies. To date, chemotherapy has not major impact in the treatment of most adult CNS tumors. The inroads made by chemotherapy in pediatric CNS malignancies suggest that novel drugs, or drug combinations, may improve therapy. Topoisomerase I (Topo I) inhibitors are a relatively new group of chemotherapy drugs with a novel mechanism of action. Drugs in this group currently undergoing clinical trials are the Camptothecin analogues Topotecan, CPT-11, and 9-aminocamptothecin. There is substantial preclinical and some clinical evidence to suggest that these drugs could be useful in the treatment of CNS malignancies. Preclinical studies with the water soluble Topo I inhibitor, Topotecan, demonstrate antineoplastic activity in a variety of CNS malignancies. In addition, Topotecan has good CNS penetration in primates, and recent preliminary phase I and II clinical trials of Topotecan in pediatric and adult CNS malignancies have been promising. In this paper, we describe the unique mechanism of action, antineoplastic activity, and radiosensitizing properties of Topo I inhibitors. We present the first report demonstrating potentiation of radiation lethality by Topotecan in a human glioma (D54) cell line. The dose enhancement ratio was 3.2 at 10% survival. Thus, there is evidence to suggest that Topo I inhibitors may be beneficial in the treatment of CNS neoplasms on the basis of their antineoplastic activity alone, as well as their radiosensitizing effects. Two clinical trials which utilize concurrent Topotecan and radiation in the treatment of pediatric and adult CNS malignancies are discussed.

Antineoplastic Agents↗
PubMed1996

Phase II study of paclitaxel in patients with recurrent malignant glioma.

PURPOSE: To assess the efficacy and toxicity of paclitaxel administered as a 3-hour infusion to patients with recurrent malignant glioma. PATIENTS AND METHODS: Adult patients with recurrent malignant glioma following radiation therapy, who had received no more than one prior chemotherapy regimen and who had a Karnofsky performance status (KPS) > or = 60, were treated with a 3-hour infusion of paclitaxel every 3 weeks. The initial dose was 210 mg/m2; dose escalation to 240 mg/m2 was allowed. Tumor response was assessed at 6-week intervals using radiographic and clinical criteria. Treatment was continued until documented tumor progression or a total of 12 paclitaxel infusions. RESULTS: Of 41 eligible patients, all were assessable for treatment toxicity and 40 (98%) were assessable for response. The response rate (disease stabilization or better) was 35%. Twenty-nine patients (71%) underwent dose escalation to 240 mg/m2 without the use of growth factors. Toxicities included alopecia (98%), nausea (22%), arthralgias (32%), CNS toxicity (24%), peripheral neuropathy (15%), cardiac toxicity (7%), and myelosuppression (10% grade 3 or 4 hematologic toxicity). No patient developed febrile neutropenia. There was one allergic reaction (2%). CONCLUSION: Paclitaxel is well tolerated at this dose schedule in patients with recurrent malignant glioma, and affords a modest response rate. Because minimal myelotoxicity was encountered in our patients, a dose-escalating phase I/II study of paclitaxel is planned to determine the maximal-tolerated dose (MTD).

Adult↗
PubMed1996

Amifostine and radiation therapy: past, present, and future.

Preclinical studies demonstrate that amifostine has the potential to selectively protect normal tissues from the harmful effects of radiation without significantly protecting neoplastic tissue. The potential value of such an agent includes reducing treatment-related toxicity and the opportunity for radiation dose escalation in the curative treatment of cancer. An increasing number of human clinical trials have been conducted that define the toxicity profile and efficacy of radioprotection by amifostine when used during fractionated radiation therapy. These trials demonstrate that amifostine is safe and practical to administer in the outpatient setting during fractionated radiation therapy. These studies also illustrate the challenge of accurately evaluating the end point of radioprotection in the clinical setting. This article reviews the recent clinical literature on amifostine, the evidence for normal tissue protection, and the lack of tumor protection by this agent, and suggests possible avenues for future investigation and application of this agent in the field of radiation oncology.

Amifostine↗
PubMed1995

Radiosurgery in the initial management of malignant gliomas: survival comparison with the RTOG recursive partitioning analysis. Radiation Therapy Oncology Group.

PURPOSE: To evaluate the impact of stereotactic radiosurgery on the survival of patients treated with malignant gliomas. METHODS AND MATERIALS: A total of 115 patients from three institutions (75 from the Joint Center for Radiation Therapy, 30 from the University of Wisconsin, and 10 from the University of Florida) were treated with a combination of surgery, external beam radiation therapy, and linac-based radiosurgery as part of similar institutional protocols from March 1988 through July 1993. Patients were stratified into six prognostic classes (classes 1-6) based on the recursive partitioning analysis of multiple prognostic factors previously reported by the Radiation Therapy Oncology Group. RESULTS: The actuarial 2-year and median survival for all patients analyzed was 45% and 96 weeks, respectively. In comparison to the results from a previously published analysis of 1578 patients entered on three Radiation Therapy Oncology Group external beam radiotherapy protocols from 1974 to 1989, those patients treated with radiosurgery had a significantly improved 2-year and median survival (p = 0.01) corresponding with a standardized mortality risk ratio of 0.51 [95% confidence interval (CI): 0.31, 0.85]. This improvement in survival was seen predominantly for the worse prognostic classes (classes 3-6). The 2-year survival for the radiosurgical patients compared with the previously reported patients was 81% vs. 76% for classes 1/2, 75% vs. 35% for class 3, 34% vs. 15% for class 4, and 21% vs. 6% for classes 5/6, respectively. Although Karnofsky performance status and prognostic class were significant on univariate analysis, only the Karnofsky score was a significant predictor of outcome on multivariate analysis. Median and 2-year survival for patients with a Karnofsky score > or = 70 was 106 weeks and 51%, respectively, as compared to 38 weeks and 0% for patients with a Karnofsky score < 70% (p = 0.001). CONCLUSIONS: The addition of radiosurgery to conventional treatment (surgery and external beam radiotherapy) of malignant gliomas appears to improve survival when compared to historical reports. These results should be interpreted with caution because the recursive partitioning model does not completely predict the prognosis of the patients treated in the present study. Although this study suggests that radiosurgery may prolong survival in patients with malignant gliomas, the role of radiosurgery in the management of these patients remains to be defined by a prospective randomized trial.

Brain Neoplasms↗
PubMed1995

Stereotactic radiosurgery for glioblastoma: a final report of 31 patients.

From February 1989 to December 1992, 31 patients who presented with an initial pathological diagnosis of glioblastoma multiforme underwent tumor debulking or biopsy, stereotactic radiosurgery, and standard radiation therapy as part of their primary treatment. Presenting characteristics in the 22 men and nine women included a median age of 57 years, Karnofsky Performance Scale score median of 80, and median tumor volume of 16.4 cm3. Stereotactic radiosurgery delivered a central dose of 15 to 35 Gy with the isocenter location, collimator size, and beam paths individualized by means of three-dimensional software developed at the University of Wisconsin. The peripheral isodose line varied from 40% to 90% with a median of 72.5% and a mode of 80%. The mean follow-up period was 12.84 months with a median of 9.5 months. Statistical analysis was performed using Kaplan-Meier analysis and log-rank comparison of risk factor groups. The parameters of age, initial Karnofsky Performance Scale score, and biopsy were significantly different in patient survival from debulking; but no difference was noted between single and multiple isocenters and patterns of steroid requirement. Radiographic recurrences were divided by location into the following categories: central (within central stereotactic radiosurgery dose), 0; peripheral (within 2 cm of central dose), 19; and distant (> 2 cm), 4. There is no evidence of recurrence in five surviving patients. Actuarial 12-month survival was 37%, with a median survival of 9.5 months. These values are similar to previous results for surgery and standard radiotherapy alone. The results suggest that the curative value of radiosurgery is significantly limited by peripheral recurrences.

Actuarial Analysis↗
PubMed1994

Stereotactic radiosurgery for glioblastoma multiforme: report of a prospective study evaluating prognostic factors and analyzing long-term survival advantage.

PURPOSE: Prospective evaluation of the toxicity and efficacy of radiosurgery with external beam radiotherapy in the management of newly diagnosed glioblastoma. METHODS AND MATERIALS: From 5/89 to 12/92, 31 out of 51 patients with glioblastoma multiforme underwent radiosurgery, in addition to 54 Gy in 1.8 Gy/fraction following biopsy (n = 12) or resection (n = 19). Eligibility required supratentorial glioblastoma, tumor not > 4 cm in > 1 axis, age > 18 years, and location > 1 cm from optic chiasm. Patient characteristics were: age 20-78 years (median = 57); 22 male, 9 female; Karnofsky score 20-90 (m = 70), and volume of 2.3-59.7 c.c. (m = 17.4). Eighteen patients were treated with 1 collimator, 5 with 2, 7 with 3, and 1 with 4; peripheral isodoses were 40-90% (m = 72.5) and minimum and maximum tumor dose ranges were 10-20 (m = 12) and 15-35 Gy (m = 18.75). Patients were followed clinically and radiographically every 8-12 weeks to analyze survival, quality of life, and toxicity. RESULTS: With a follow-up of 12-171 weeks, 8 out of 31 (26%) patients are alive. Median survival is 42 weeks. Twelve and 24-month actuarial survival are 38 and 28%. Comparison of the 2-year survival with previous Radiation Therapy Oncology Group patients was carried out using a nonparametric recursive partitioning technique and the observed vs. expected values are 28 vs. 9.7% (p < 0.05). Extent of resection and performance status were associated with improved survival in a multivariate analysis. No significant acute toxicity was encountered. Four patients (13%) developed clinically significant necrosis verified by biopsy or positron emission tomography scan at 9-59 weeks after radiosurgery. CONCLUSION: The improvement in median survival in broadly selected glioblastoma patients treated with radiosurgery is difficult to determine, but the 2-year survival may be superior. Future randomized trials of radiosurgery are recommended, and ad hoc use of this modality should be discouraged.

Adult↗