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Minesh Mehta

Publications and source records attributed to Minesh Mehta.

At least 37 records · Page 2Linked to original sources
PubMed2005

Are more aggressive therapies able to improve treatment of locally advanced non-small cell lung cancer: combined modality treatment?

Non-small cell lung cancer continues to be a major oncologic problem, with approximately 3-month increase in median survival per decade since the 1970s. Thus, newer strategies are needed to improve outcomes in non-small cell lung cancer. New treatment strategies include optimizing and intensifying radiation therapy (RT) delivery, as well as improving systemic therapy with newly developed targeted agents. Three-dimensional treatment planning is a key technology for optimizing RT delivery. Additionally, improvements in radiation therapy will clearly require better target delineation and dose-intensification of RT. With newer, possibly less toxic agents such as the epidermal growth factor receptor inhibitors, RT and systemic therapy (with chemo- and/or targeted therapies) may be optimized in the concurrent setting, perhaps reserving more cytotoxic regimens either for the induction or maintenance settings.

Antineoplastic Agents↗
PubMed2005

Strategies for enhanced radiation delivery in patients with lung cancer.

Since the 1970s primary management for regionally advanced non-small cell lung cancer has shifted from radiotherapy alone to sequential chemoradiation to concurrent chemoradiation. The increase in survival with these approaches has been small; an approximately 3-4 month per decade increase in median survival. Future avenues to improve on these outcomes could involve: i)dose-intense radiotherapy; ii) better target delineation; and iii) combining molecularly targeted agents with optimised radiation therapy. However, to accomplish this, techniques to control tumour motion and decrease toxicity must be developed.

Animals↗
PubMed2005

Potential for radiation therapy technology innovations to permit dose escalation for non-small-cell lung cancer.

BACKGROUND: Innovations in radiation therapy (RT) technology could have the potential to allow for radiation dose escalation by evaluating tumor motion, minimizing and compensating for motion, and evaluating delivery technologies such as 3-dimensional (3D) conformal radiation therapy (CRT) and intensity-modulated RT (IMRT) using tomotherapy. MATERIALS AND METHODS: Ninety different RT plans were generated using 3 different treatment techniques for 10 patients. These were evaluated using dosimetric tools such as dose-volume histogram (DVH) analysis, tumor equivalent uniform dose (EUD), and dosimetric parameters predictive for lung toxicity, such as the volume of lung receiving > 20 Gy of radiation (V20) and the normalized mean total radiation dose to the lung (NTDmean). The 3 techniques studied included free breathing using 3D CRT, 3D CRT with maximum-inspiration breath-hold (MIBH) to minimize tumor motion, and IMRT delivery with MIBH; the combination of 3 separate planning treatment-volume sets resulted in the generation of 90 different treatment plans. To plan these, patients underwent treatment-planning computed tomography in MIBH and free breathing followed by simulation with measurement of tumor motion and generation/evaluation of DVHs, EUDs, V20, and NTDmean. RESULTS: Average tumor motion was 1.54 cm in the cephalocaudad directions, 1.26 cm in the anteroposterior directions, and 0.56 cm in the lateral directions between maximum inspiration and expiration. Maximum-inspiration breath-hold produced superior lung sparing evidenced by lower V20 and NTDmean values, and these parameters predicted lower modeled pneumonitis rates. Tomotherapy-based IMRT provided further lung sparing. CONCLUSION: Treatment in MIBH results in lower V20 and NTDmean values and lower modeled pneumonitis rates. This effect is enhanced by the use of IMRT. The use of MIBH with IMRT may therefore aid in escalating the dose in RT.

Adenocarcinoma↗
PubMed2004

Phase I study pilot arms of radiotherapy and carmustine with temozolomide for anaplastic astrocytoma (Radiation Therapy Oncology Group 9813): implications for studies testing initial treatment of brain tumors.

PURPOSE: To determine the safety and toxicity of carmustine (BCNU) and temozolomide (TMZ) with radiotherapy (RT) in newly diagnosed anaplastic astrocytoma. METHODS AND MATERIALS: Patients >18 years old with anaplastic astrocytoma, a Karnofsky performance status score of > or =60, and adequate pulmonary function were eligible. All patients provided informed consent. Standard RT started within 5 weeks of diagnosis. In both arms, 150 mg/m(2) of TMZ was given on Days 1-5 of RT. In Arm 1, 200 mg/m(2) of carmustine was given on Day 1 of RT. In Arm 2, 150 mg/m(2) of carmustine was given on Day 5 of RT. After RT, TMZ and carmustine were repeated for a total of six cycles. RESULTS: A total of 15 and 14 patients were enrolled in the two pilot arms. Because of hematologic and pulmonary toxicities, dose reductions by the second cycle of therapy occurred in >70% of the patients in Arm 1 and >50% in Arm 2 despite a reduction in the carmustine dose. CONCLUSION: The results of these pilot studies have implications for the design of studies testing the initial treatment of brain tumors. Because of the poor tolerance of the combination, the multicooperative group Phase III study consists of two randomized arms of single-agent carmustine vs. single-agent TMZ.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Phase II study of neoadjuvant 1, 3-bis (2-chloroethyl)-1-nitrosourea and temozolomide for newly diagnosed anaplastic glioma: a North American Brain Tumor Consortium Trial.

BACKGROUND: Temozolomide (TMZ) and 1, 3-bis (2-chloroethyl)-1-nitrosourea (BCNU) are reported to be active agents in anaplastic glioma (AG). TMZ has also been shown to deplete alkyltransferase, a DNA repair enzyme that contributes to nitrosourea resistance. The objective of the current study was to determine the efficacy and toxicity profile of a combination of these agents before radiotherapy in newly diagnosed AG. METHODS: Eligibility criteria included histologically confirmed newly diagnosed AG with measurable enhancing disease, a Karnofsky performance score (KPS) > or = 60, normal pulmonary function, and normal laboratory parameters. In addition, informed consent was obtained from all patients. BCNU given at a dose of 150 mg/m(2) intravenously was followed after 2 hours by TMZ given at a dose of 550 mg/m(2) orally on Day 1 of a 42-day cycle to a maximum of 4 cycles, unless there was tumor progression or unacceptable toxicity. RESULTS: Forty-one eligible patients were accrued. Their median age was 40 years. Seventy-six percent of patients had a KPS of 90-100. The histology was 81% anaplastic astrocytoma, 12% anaplastic oligodendroglioma, and 7% mixed tumors. Twenty-two percent of patients did not complete 4 cycles because of toxicity, mainly hematologic. Forty-six percent of patients experienced Grade 3 or 4 (according to National Cancer Institute Common Toxicity Criteria) thrombocytopenia. Twenty percent had Grade 4 granulocytopenia. Two patients died while receiving therapy, 1 of progressive disease and the other of Pneumocystis carinii pneumonia. The complete and partial response rates were 2% and 27% respectively. An additional 54% of patients had stable disease. Seventeen percent developed progressive disease (10% after the first cycle and 7% after the second cycle). CONCLUSIONS: This neoadjuvant strategy was associated with significant myelosuppression and a modest response rate in patients with newly diagnosed AG.

Adolescent↗
PubMed2004

The contribution of epidermal growth factor receptor (EGFR) signaling pathway to radioresistance in human gliomas: a review of preclinical and correlative clinical data.

PURPOSE: The epidermal growth factor receptor (EGFR) pathway is frequently upregulated in high-grade gliomas via gene amplification and by specific mutations that render EGFR constitutively active (EGFRvIII). METHODS AND MATERIALS: This review highlights EGFR's role in mediating radiation resistance in gliomas: underlying molecular mechanisms, with discussion of relevant preclinical and clinical correlative data. RESULTS: Preclinical and emerging clinical data suggest that EGFR signaling plays a potentially important role in mediating radiation resistance in human gliomas. CONCLUSIONS: Targeting EGFR alone, or in combination with its downstream mediators, represents a promising new approach for the management of glioma patients.

Animals↗
PubMed2004

A phase I study of Topotecan, as a radiosensitizer, for thoracic malignancies.

PURPOSE: To determine the maximum-tolerated dose (MTD) of daily Topotecan with full-dose thoracic radiotherapy (XRT). METHODS AND MATERIALS: Patients with advanced thoracic malignancies requiring full dose radiation received daily I.V. Topotecan prior to each daily session of XRT to 60 Gy over 6 weeks. Dose levels (and subjects studied at each) have been 0.2 (N=7), 0.3 (N=5), 0.4 (N=7), and 0.5mg/m(2) per day (N=5) in a best-of-five design. Tumor response was assessed at 4-8 weeks after completion of therapy. RESULTS: From March 1995 to December 1999, a total of 24 patients were treated. The MTD of Topotecan was 0.4 mg/m(2) per day, based on dose limiting toxicities (DLTs) observed at 0.5 mg/m(2) per day, which were grade 4 hematological toxicities or diarrhea and grade 3 esophagitis. Tumor responses included: zero complete response (CR), nine partial responses (PR), five stable disease (SD), nine progressive disease (PD) and one not evaluated (NE). Additionally, local response was also assessed separately (within the XRT ports) and there were 10 PR, 12 SD, 1 PD, and 1 NE. CONCLUSION: the MTD of Topotecan with concomitant thoracic radiotherapy is 0.4 mg/m(2) per day. The DLTs observed were grade 4 diarrhea, grade 3 esophagitis and grade 4 hematological toxicities. Based on the known radiosensitizing effect of Topotecan, this dose is recommended for phase II testing.

Adult↗
PubMed2004

The impact of mid-treatment MRI on defining boost volumes in the radiation treatment of glioblastoma multiforme.

Radiation therapy is a central modality in the treatment of glioblastoma multiforme (GBM). Integral to adequate radiation therapy delivery is the appropriate determination of tumor volume and extent at the time treatment is being delivered. As a matter of routine practice, radiation therapy treatment fields are designed based on tumor volumes evident on pre-operative or immediate post-operative MRIs; another MRI is generally not obtained for planning boost fields. In some instances the time interval from surgery to radiotherapy initiation is up to 5 weeks and the boost or "cone-down phase" commences 4-5 weeks later. The contrast enhanced T1 MRI may not be a totally reliable indicator of active tumor, especially in regions where such blood-brain barrier breakdown has not occurred. Moreover, these volumes may change during the course of treatment. This may lead to a geographic miss when mid-treatment boost volumes are designed based on a pre-radiotherapy MRI. The goal of this study is to examine how a mid-treatment MRI impacts the delineation and definition of the boost volume in GBM patients in comparison to the pre-treatment MRI scan, particularly when the tumor-specific agent Motexafin-Gadolinium is used.

Brain Neoplasms↗
PubMed2004

Helical tomotherapy as a means of delivering accelerated partial breast irradiation.

A novel treatment approach utilizing helical tomotherapy for partial breast irradiation for patients with early-stage breast cancer is described. This technique may serve as an alternative to high dose-rate (HDR) interstitial brachytherapy and standard linac-based approaches. Through helical tomotherapy, highly conformal irradiation of target volumes and avoidance of normal sensitive structures can be achieved. Unlike HDR brachytherapy, it is noninvasive. Unlike other linac-based techniques, it provides image-guided adaptive radiotherapy along with intensity modulation. A treatment planning CT scan was obtained as usual on a post-lumpectomy patient undergoing HDR interstitial breast brachytherapy. The patient underwent catheter placement for HDR treatment and was positioned prone on a specially designed position-supporting mattress during CT. The planning target volume (PTV) was defined as the lumpectomy bed plus a 20 mm margin. The prescription dose was 34 Gy (10 fx of 3.4 Gy) in both the CT based HDR and on the tomotherapy plan. Cumulative dose-volume histograms (DVHs) were generated and analyzed for the target, lung, heart, skin, pectoralis muscle, and chest wall for both HDR brachytherapy and helical tomotherapy. Dosimetric coverage of the target with helical tomotherapy was conformal and homogeneous. "Hot spots" (> or =150% isodose line) were present around implanted dwell positions in brachytherapy plan whereas no isodose lines higher than 109% were present in the helical tomotherapy plan. Similar dose coverage was achieved for lung, pectoralis muscle, heart, chest wall and breast skin with the two methods. We also compared our results to that obtained using conventional linac-based three dimensional (3D) conformal accelerated partial breast irradiation. Dose homogeneity is excellent with 3D conformal irradiation, and lung, heart and chest wall dose is less than for either HDR brachytherapy or helical tomotherapy but skin and pectoral muscle doses were higher than with the other techniques. Our results suggest that helical tomotherapy can serve as an effective means of delivering accelerated partial breast irradiation and may offer superior dose homogeneity compared to HDR brachytherapy.

Brachytherapy↗
PubMed2004

Motexafin gadolinium: a clinical review of a novel radioenhancer for brain tumors.

Despite recent advances in both technology and molecular targeting, little progress has been made in the management of most malignancies of the brain, especially brain metastases. In an effort to increase the therapeutic ratio of external beam radiation treatments, radiosensitizers and enhancers have been investigated. Motexafin gadolinium is a new drug with radioenhancing properties and a unique mechanism of action that may increase the therapeutic index of whole brain radiotherapy for patients with brain metastases. The rationale for the use of this drug as well as its current and future role as a radiation enhancer in the management of brain tumors is reviewed.

Antineoplastic Agents↗
PubMed2003

RSR13 plus cranial radiation therapy in patients with brain metastases: comparison with the Radiation Therapy Oncology Group Recursive Partitioning Analysis Brain Metastases Database.

PURPOSE: This phase II, open-label, multicenter study assessed the efficacy and safety of the potential radiation enhancer RSR13 plus cranial radiation therapy (RT) in patients with brain metastases. The primary end point was patient survival in comparison with the Radiation Therapy Oncology Group Recursive Partitioning Analysis Brain Metastases Database (RTOG RPA BMD). PATIENTS AND METHODS: Eligibility criteria were age > or = 18 years, Karnofsky performance score > or = 70, and brain metastases with solid tumor histology. Patients received cranial RT, 30 Gy in 10 fractions of 3 Gy each, preceded by RSR13, 50 to 100 mg/kg intravenously over 30 minutes. Univariate and multivariate comparisons of survival and cause of death were made between class II study patients and RTOG BMD patients. RESULTS: Fifty-seven RPA class II patients were enrolled. With a minimum follow-up of 24 months, the median survival time and 1- and 2-year survival rates were 6.4 months, 23%, and 11% for the RSR13-treated patients compared with 4.1 months, 15%, and 3% for the RTOG BMD patients (P =.0174). In an exact-matched case analysis (n = 38), median survival time for RSR13 patients was 7.3 months versus 3.4 months for the RTOG BMD patients (P =.006). There was a 54% reduction in the risk of death for RSR13 patients (P =.0267). RSR13-related adverse events of greater than or equal to grade 3 toxicity that occurred in more than one patient included hypoxia, headache, anemia, fatigue, hypertension, and intracranial hypertension. CONCLUSION: RSR13 plus cranial RT resulted in a significant improvement in survival, as well as a reduction in death due to brain metastases, compared with class II patients in the RTOG BMD.

Adult↗
PubMed2003

Phase II evaluation of temozolomide and 13-cis-retinoic acid for the treatment of recurrent and progressive malignant glioma: a North American Brain Tumor Consortium study.

PURPOSE: Temozolomide (TMZ) and 13-cis-retinoic acid (cRA) have shown activity in prior single-agent trials of recurrent malignant gliomas (MG). This phase II trial evaluated efficacy and toxicity of combination temozolomide and cRA treatment in recurrent MG. PATIENTS AND METHODS: Adults with recurrent supratentorial MG for whom surgery, radiation, and/or chemotherapy failed were eligible. Treatment included oral TMZ 150 or 200 mg/m2/d, days 1 through 5, and cRA 100 mg/m2/d, days 1 to 21, every 28 days. Primary end point was progression-free survival at 6 months (PFS 6); secondary end points included response, survival, and PFS12. RESULTS: Eighty-eight eligible patients (glioblastoma multiforme [n = 40]; anaplastic gliomas [n = 48; astrocytoma, 28; oligodendroglioma, 14; mixed glioma, six]) received treatment. PFS 6 was 43% (95% confidence interval [CI], 33% to 54%) and PFS12 was 16% (95% CI, 10% to 26%). Median overall PFS was 19 weeks (95% CI, 16 to 27 weeks), and median overall survival (OS) was 47 weeks (95% CI, 36 to 58 weeks). OS was 46% (95% CI, 36% to 57%) at 52 weeks and 21% (95% CI, 13% to 31%) at 104 weeks. Of 84 assessable patients, there were two (3%) complete responses and eight (12%) partial responses (complete plus partial response, 15%). Among 499 treatment cycles, the most common grade 3/4 events included granulocytopenia (1.8%), thrombocytopenia (1.4%), and hypertriglyceridemia (1.2%). CONCLUSION: TMZ and cRA were active, exceeding our 20% thresholds for PFS 6 success, assuming 20% improvement over our previously reported database (glioblastoma multiforme: expected, 30%; observed, 32%; anaplastic glioma: expected, 40%; observed, 50%).

Adult↗
PubMed2003

Image guidance for precise conformal radiotherapy.

PURPOSE: To review the state of the art in image-guided precision conformal radiotherapy and to describe how helical tomotherapy compares with the image-guided practices being developed for conventional radiotherapy. MATERIALS AND METHODS: Image guidance is beginning to be the fundamental basis for radiotherapy planning, delivery, and verification. Radiotherapy planning requires more precision in the extension and localization of disease. When greater precision is not possible, conformal avoidance methodology may be indicated whereby the margin of disease extension is generous, except where sensitive normal tissues exist. Radiotherapy delivery requires better precision in the definition of treatment volume, on a daily basis if necessary. Helical tomotherapy has been designed to use CT imaging technology to plan, deliver, and verify that the delivery has been carried out as planned. The image-guided processes of helical tomotherapy that enable this goal are described. RESULTS: Examples of the results of helical tomotherapy processes for image-guided intensity-modulated radiotherapy are presented. These processes include megavoltage CT acquisition, automated segmentation of CT images, dose reconstruction using the CT image set, deformable registration of CT images, and reoptimization. CONCLUSIONS: Image-guided precision conformal radiotherapy can be used as a tool to treat the tumor yet spare critical structures. Helical tomotherapy has been designed from the ground up as an integrated image-guided intensity-modulated radiotherapy system and allows new verification processes based on megavoltage CT images to be implemented.

Animals↗
PubMed2003

Phase III study comparing three cycles of infusional carmustine and cisplatin followed by radiation therapy with radiation therapy and concurrent carmustine in patients with newly diagnosed supratentorial glioblastoma multiforme: Eastern Cooperative Oncology Group Trial 2394.

PURPOSE: This phase III Eastern Cooperative Oncology Group-Southwest Oncology Group intergroup study was conducted to determine whether three 72-hour infusions of carmustine (BiCNU) and cisplatin administered monthly before external-beam radiotherapy would improve the survival of patients with newly diagnosed glioblastoma multiforme. The control arm consisted of radiation with standard adjuvant BiCNU. PATIENTS AND METHODS: A total of 223 patients were accrued from 1996 to 1999. Of these, 219 patients were eligible; 109 were randomly assigned to the experimental arm, and 110 were randomly assigned to the control arm. Randomization was stratified by age, performance status, and extent of resection. RESULTS: The median age of the patients was 55 years; 55% were male, 93% were white, 26% had a biopsy only, and 84% were ambulatory. Treatment arms were well balanced with respect to baseline characteristics. Median follow-up time of the 15 patients still alive at the time of analysis was 3.3 years (range, 2 to 5 years). Median survival times for the standard and experimental arms were 11.2 and 11.0 months (P =.33, two-sided log-rank test), and survival at 1 year was 45% versus 44%, respectively. Fifty-six percent of patients received all three cycles of BiCNU/cisplatin, 12% received two cycles, and 31% received only one cycle. Toxicity was primarily hematologic and was more common in the experimental arm (P <.01). CONCLUSION: This study demonstrates that 72-hour infusions of BiCNU and cisplatin followed by radiation do not improve median survival, survival at 1 year, or time to progression. Furthermore, this treatment requires more time in the hospital and is associated with more serious toxicities than standard therapy.

Adult↗
PubMed2003

Craniospinal treatment with the patient supine.

Radiotherapy of the craniospinal axis in young children is frequently complicated by the need for access to the patient's airway for sedation and anesthesia delivery or by frequent, unanticipated movement. Positioning the patient supine, instead of in the conventional prone position, allows the use of immobilization facemasks with body molds and more positive patient fixation, and improved airway access. The procedure for establishing the various fields differs from the prone approach. In this paper, we describe the methodology to achieve successful supine positioning.

Age Factors↗
PubMed2003

Temporal and gender-related trends in brain metastases from lung and breast cancer.

Increased duration of cancer survival may allow a longer window for detection of metastases, including brain metastases. Using the entire population of Olmsted County, Minnesota, we looked at trends in the rate of brain metastases in people diagnosed with primary lung or breast cancers between January 1, 1988, and December 31, 2001. Yearly rates of brain metastases detection following the primary tumors were calculated from a combination of medical record and SEER database information. Trends in rates and gender differences were assessed. There was no discernible increase in the rates of brain metastases secondary to lung or breast cancer during the period of observation. However, women were twice as likely as men to have brain metastases detected following a primary lung cancer. This difference was constant over the time period. This twofold difference in brain metastases detected in women versus men with lung cancer deserves further evaluation and confirmation.

Adult↗