Showing papers by "Moshe H. Maor published in 2005"

Central nervous system cancers: Clinical Practice Guidelines in Oncology.

Abstract: Primary and metastatic tumors of the central nervous system are a heterogeneous group of neoplasms with varied outcomes and management strategies. Recently, improved survival observed in 2 randomized clinical trials established combined chemotherapy and radiation as the new standard for treating patients with pure or mixed anaplastic oligodendroglioma harboring the 1p/19q codeletion. For metastatic disease, increasing evidence supports the efficacy of stereotactic radiosurgery in treating patients with multiple metastatic lesions but low overall tumor volume. These guidelines provide recommendations on the diagnosis and management of this group of diseases based on clinical evidence and panel consensus. This version includes expert advice on the management of low-grade infiltrative astrocytomas, oligodendrogliomas, anaplastic gliomas, glioblastomas, medulloblastomas, supratentorial primitive neuroectodermal tumors, and brain metastases. The full online version, available at NCCN.org, contains recommendations on additional subtypes.

Treatment planning with protons for pediatric retinoblastoma, medulloblastoma, and pelvic sarcoma: How do protons compare with other conformal techniques?

Abstract: Purpose: To calculate treatment plans and compare the dose distributions and dose–volume histograms (DVHs) for photon three-dimensional conformal radiation therapy (3D-CRT), electron therapy, intensity-modulated radiation therapy (IMRT), and standard (nonintensity modulated) proton therapy in three pediatric disease sites. Methods and Materials: The tumor volumes from 8 patients (3 retinoblastomas, 2 medulloblastomas, and 3 pelvic sarcomas) were studied retrospectively to compare DVHs from proton therapy with 3D-CRT, electron therapy, and IMRT. In retinoblastoma, several planning techniques were analyzed: A single electron appositional beam was compared with a single 3D-CRT lateral beam, a 3D-CRT anterior beam paired with a lateral beam, IMRT, and protons. In medulloblastoma, three posterior fossa irradiation techniques were analyzed: 3D-CRT, IMRT, and protons. Craniospinal irradiation (which consisted of composite plans of both the posterior fossa and craniospinal components) was also evaluated, primarily comparing spinal irradiation using 3D-CRT electrons, 3D-CRT photons, and protons. Lastly, in pelvic sarcoma, 3D-CRT, IMRT, and proton plans were assessed. Results: In retinoblastoma, protons resulted in the best target coverage combined with the most orbital bone sparing (10% was the mean orbital bone volume irradiated at ≥5 Gy for protons vs. 25% for 3D-CRT electrons, 69% for IMRT, 41% for a single 3D lateral beam, 51% for a 3D anterolateral beam with a lens block, and 65% for a 3D anterolateral beam without a lens block). A single appositional electron field was the next best technique followed by other planning approaches. In medulloblastoma, for posterior fossa and craniospinal irradiation, protons resulted in the least dose to the cochlea (for only posterior fossa irradiation at ≥20 Gy, 34% was the mean cochlear volume irradiated for protons, 87% for IMRT, 89% for 3D-CRT) and hypothalamus-pituitary axis (for only posterior fossa irradiation at ≥10 Gy, 21% was the mean hypothalamus-pituitary volume irradiated for protons, 81% for IMRT, 91% for 3D-CRT); additional dose reductions to the optic chiasm, eyes, vertebrae, mandible, thyroid, lung, kidneys, heart, and liver were seen. Intensity-modulated radiotherapy appeared to be the second best technique for posterior fossa irradiation. For spinal irradiation 3D-CRT electrons were better than 3D-CRT photons in sparing dose to the thyroid, heart, lung, kidney, and liver. With pelvic sarcoma, protons were superior in eliminating any dose to the ovaries (0% of mean ovarian volume was irradiated at ≥2 Gy with protons) and to some extent, the pelvic bones and vertebrae. Intensity-modulated radiotherapy did show more bladder dose reduction than the other techniques in pelvic sarcoma irradiation. Conclusions: In the diseases studied, using various techniques of 3D-CRT, electrons, IMRT, and protons, protons are most optimal in treating retinoblastomas, medulloblastomas (posterior fossa and craniospinal), and pelvic sarcomas. Protons delivered superior target dose coverage and sparing of normal structures. As dose–volume parameters are expected to correlate with acute and late toxicity, proton therapy should receive serious consideration as the preferred technique for the treatment of pediatric tumors.

YKL-40 expression is associated with poorer response to radiation and shorter overall survival in glioblastoma.

Abstract: Purpose: YKL-40 is a secreted protein that has been reported to be overexpressed in epithelial cancers and gliomas, although its function is unknown. Previous data in a smaller sample set suggested that YKL-40 was a marker associated with a poorer clinical outcome and a genetically defined subgroup of glioblastoma. Here we test these findings in a larger series of patients with glioblastoma, and in particular, determine if tumor YKL-40 expression is associated with radiation response. Experimental Design: Patients ( n = 147) with subtotal resections were studied for imaging-assessed changes in tumor size in serial studies following radiation therapy. An additional set ( n = 140) of glioblastoma patients who underwent a gross-total resection was tested to validate the survival association and extend them to patients with minimal residual disease. Results: In the subtotal resection group, higher YKL-40 expression was significantly associated with poorer radiation response, shorter time to progression and shorter overall survival. The association of higher YKL-40 expression with poorer survival was validated in the gross-total resection group. In multivariate analysis with both groups combined ( n = 287), YKL-40 was an independent predictor of survival after adjusting for patient age, performance status, and extent of resection. YKL-40 expression was also compared with genetically defined subsets of glioblastoma by assessing epidermal growth factor receptor amplification and loss at chromosome 10q, two of the common recurring aberrations in these tumors, using fluorescent in situ hybridization. YKL-40 was significantly associated with 10q loss. Conclusions: The findings implicate YKL-40 as an important marker of therapeutic response and genetic subtype in glioblastomas and suggest that it may play an oncogenic role in these tumors.

Outcome variation among "radioresistant" brain metastases treated with stereotactic radiosurgery

Abstract: OBJECTIVE: To determine the influence of histopathological diagnosis on the outcome of radioresistant brain metastases treated with stereotactic radiosurgery (SRS) METHODS: Patients (n = 189) with radioresistant brain metastases (n = 264) were consecutively treated with SRS between August 1991 and July 2002 The primary site of brain metastases was melanoma (n = 103), renal cell carcinoma (n = 77), and sarcoma (n = 9) The median age of the patients was 52 years, and the median Karnofsky Performance Scale score was 80 Initial brain metastasis presentation was single in 112 patients (59%) The median SRS dose was 18 Gy (range, 10-24 Gy) The median tumor volume was 16 cm 3 (range, 006-275 cm 3 ) The median follow-up of all patients was 74 months (range, 016-52 mo) RESULTS: The actuarial freedom from progression after 1 year was 64% for renal cell carcinoma patients, 47% for melanoma patients, and 0% for sarcoma patients (P < 0001) The median survival time for all patients from time of SRS was 75 months The rate of 1-year survival was 40% for renal cell carcinoma patients, 25% for melanoma patients, and 22% for sarcoma patients (P = 00354) The incidence of neurological death was lower among patients diagnosed with renal cell carcinoma (31%) than among patients with melanoma (66%) or sarcoma (60%) (P = 0001) CONCLUSION: Survival after SRS is significantly worse for patients with melanoma and sarcoma brain metastases compared with patients with renal cell carcinoma Our data show that progressive brain metastases seem to cause most of the cancer-related deaths among patients with SRS-treated melanoma and sarcoma brain metastases Future investigations using chemotherapy or novel agents to enhance the effectiveness of SRS to melanoma and sarcoma brain metastases seem warranted

Case-control study of stereotactic radiosurgery for recurrent glioblastoma multiforme.

Abstract: Object. The role of stereotactic radiosurgery (SRS) for recurrent glioblastoma multiforme (GBM) was evaluated in a case—control study. Methods. All patients who underwent SRS for recurrent GBM before March 2003 formed the case group. A control group of patients who did not undergo SRS was created from an institutional database, and each case was matched for known prognostic factors in GBM. The medical and neuroimaging records of all the patients were reviewed, and survival and treatment outcomes were recorded. The case and control groups were well matched with regard to demographics and pre-SRS interventions. In the control group, the date on which magnetic resonance imaging identified a recurrent lesion that would have been eligible for SRS was deemed the “SRS” date. The number of surgeries performed in the control group was statistically higher than that in the case group. The median duration of overall survival from diagnosis was 26 months in the case group and 23 months in the control group. From the ...

Brain Tumors: Diagnosis, Surgery and Radiotherapy, and Supportive Care

Abstract: This chapter covers the approach taken by the M. D. Anderson Cancer Center Division of Pediatrics in the diagnosis, treatment, and supportive care of children with central nervous system (CNS) tumors. The unique aspects of state-of-the-art radiotherapy and neurosurgery techniques available to children are discussed as well as our comprehensive supportive-care program. The specialized care of children with neurofibromatosis and CNS tumors are described. Chemotherapy programs and clinical trials for children with CNS tumors are discussed in Chapter 4, “Brain Tumors: Chemotherapy and Investigational Therapy.”

Brain Tumors: Chemotherapy and Investigational Therapy

Abstract: This chapter covers the methods used in staging and treating the most common-types of childhood brain tumors, with emphasis on the chemotherapy-radiotherapy programs and clinical trials of the Division of Pediatrics at M. D. Anderson Cancer Center. For tumor types such as medulloblastoma, in which the choice of chemotherapy and radiotherapy is interactive or concurrent, the radiation dose and timing are also discussed. The use of chemotherapy regimens to reduce or delay irradiation in young children is also addressed.