Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical and neuro-endocrine data of seven young male patients with suprasellar germinomas seen between 1984 and 1992 are reported. The most common initial symptom was 'idiopathic' central diabetes insipidus (DI), which occurred in all seven patients. The time interval between the appearance of this first clinical sign and the definitive diagnosis of a suprasellar germinoma ranged from 3 to 66 months. Raised prolactin levels and growth hormone deficiency were indicators of a process located in the hypothalamic-pituitary region. An increased beta-HCG level in the serum or the CSF confirmed the diagnostic suspicion of a germinoma and was helpful as a tumor marker in follow-up. Neuro-radiologic studies (CT or MRI) were also disappointing in the early stage when patients presented only with DI. Later on, as patients developed additional symptoms or signs related to the tumor, imaging studies were positive. Given the variable rate of tumor progression, the nonspecific early signs of hypothalamic-pituitary dysfunction (DI) as well as the often negative early imaging studies, the diagnosis of suprasellar germinoma is difficult but should always be considered in the presence of so-called 'idiopathic' central DI. Repeated brain MRIs are mandatory in young patients with idiopathic DI in order not to miss an underlying suprasellar germinoma.
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PMID:Suprasellar germinomas in childhood and adolescence: diagnostic pitfalls. 982 22

Efficiency of chemotherapy (CT) on non removable HGG has not been proven and neoadjuvant brain irradiation (RT) following biopsy is the standard treatment. We aimed to define whether combination of polychemotherapy and radiotherapy is synergistic in non removable HGG. It has been proven that F, CDDP and VP16 can reach therapeutic levels in brain after intravenous standard dose injections. The aim of this study was to assess that (i) neoadjuvant CT is safe; (ii) feasibility and efficacions of F (100 mg/m2.d1)/CDDP (100 mg/m2.d1-3 TD)/VP16 (75 mg/m2.d1-3) q21-28d regimen; (iii) Delayed RT is not unsafe: RT was performed when tumor progression or toxicity appeared. This study included 16 patients with symptomatic non removable HGG. Two of them had anaplastic gliomas and 14 glioblastomas multiforme. None of them had a prior chemotherapy regimen. Objective response was evaluated with CT scan or MRI during chemotherapy. Toxicity was moderate and mainly hematological (grade III-IV thrombopenia = 10/67 cycles; leukopenia = 13/67). Objective response rates were 5/16 (31 p. 100) (CR = 1; PR = 4; Median duration of response: 20 weeks). Median survival was 55 weeks in the 14 grade IV patients. Three/16 patients are still alived with respectively 22, 30, 40 months survival: These results confirm the neoadjuvant chemotherapy efficacy. It may be a useful tool before RT for non removable HGG.
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PMID:[Chemotherapy of malignant inoperable gliomas. The association of fotemustine-cisplatine-etoposide as neoadjuvants]. 1069 59

With the recent approval of reimbursement for positron emission tomography (PET), it has become important to clarify the utility of this diagnostic study. We evaluated the utility of PET to distinguish radiation necrosis from recurrent tumor in a retrospective review of patients with primary glial neoplasms. Fifteen patients had preoperative contrast-enhanced MRI and PET images followed by stereotactic biopsy or craniotomy and histological confirmation. The sensitivity of PET was 43% (6/14) and the specificity was 100% (1/1). We examined the sensitivity of PET as a function of volumetric contrast enhancement on MRI. Eighty percent of true-positive PET studies occurred with volume enhancement greater than 10 cm(3). Seventy-five percent of false negatives occurred with volume enhancement less than 6 cm(3). Given the clinical significance of distinguishing tumor progression from radiation necrosis, we believe that PET is insufficient to resolve radiation necrosis versus tumor progression.
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PMID:Distinguishing recurrent tumor and radiation necrosis with positron emission tomography versus stereotactic biopsy. 1085 90

Intramedullary spinal cord astrocytomas are uncommon tumors. They are the most common spinal cord tumor in children and in adults are second only to ependymomas in frequency of occurrence. Low-grade histology predominates with high-grade lesions comprising only ten to fifteen percent of pediatric tumors and a slightly higher proportion in adults. Presenting symptoms typically evolve over months to years with regional back pain the most commonly reported initial complaint. Malignant tumors produce rapid neurological deterioration. MRI is the diagnostic modality of choice: spinal cord astrocytomas are iso- to slightly hypointense on T1, hyperintense on T2 and commonly have associated cysts. They enhance less intensely and are more eccentric than ependymomas. The goals of surgical intervention are to obtain a tissue diagnosis and resect as much tumor as possible without adversely affecting neurological function. Astrocytomas are infiltrating neoplasms and total resection is not generally possible. Somatosensory and motor evoked potential monitoring are routinely used but it is unclear if they improve outcomes. The operating microscope and bipolar cautery are essential surgical tools; the ultrasound and ultrasonic surgical aspirator are useful surgical adjuncts. Laminectomy is performed on adults while laminoplasty is favored for pediatric patients. Outcome for low-grade astrocytomas is less favorable than that of ependymomas with regard to both recurrence and function though many have prolonged survival. There is no correlation of extent of resection and recurrence. Outcome for high-grade tumors is extremely poor; tumor progression is relentless; median survival is thirteen months in children and six months in adults.
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PMID:Spinal cord astrocytomas: presentation, management and outcome. 1101 38

Although the efficacy of the nitrosourea-based combination chemotherapy procarbazine, N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosurea, and vincristine (PCV) has been previously demonstrated in the setting of anaplastic/intermediate-grade gliomas, the benefit for glioblastoma patients remains unproven. In the current study, we sought to determine whether the addition of alpha-difluoromethylornithine (eflornithine), an inhibitor of ornithine decarboxylase, which has shown encouraging results in the setting of recurrent glioma patients, to a nitrosourea-based therapy (PCV) would constitute a more effective adjuvant therapy in the treatment of glioblastoma multiforme patients in the postradiation therapy setting. Following conventional radiation therapy, 272 glioblastoma (GBM) patients were randomized to receive either alpha-difluoromethylornithine-PCV (DFMO-PCV; 134 patients) or PCV alone (138 patients), with survival and time to tumor progression being the primary endpoints. The starting dosage of DFMO was 3.0 g/m2 p.o. q8h for 14 days before and after treatment with N-(2-chloroethyl)-N-cyclohexyl-N-nitrosurea; PCV was administered as previously described1. Clinical and radiological (Gadolinium-enhanced MRI) follow-ups were nominally at the end of each 6 or 8 week cycle (PCV at 6 weeks; DFMO-PCV at 8 weeks). Laboratory evaluations for hematologic and other adverse effects were at 2 week intervals. There was no difference in median survival or median time-to-tumor progression between the two treatment groups, as measured from day of commencement of postradiotherapy chemotherapy [MS (months): DFMO-PCV, 10.5; Overall survival, as measured from time of tumor diagnosis at first surgery, was 13.3 and 14.2 months at the median and 6.2 and 8.7% at 5 years, respectively, for the DFMO-PCV and PCV arms. The treatment effect was unchanged after adjustment for age, performance status (KPS), extent of surgery, and other factors using the multivariate Cox proportional hazard model. Adverse effects associated with DFMO consisted of gastrointestinal (diarrhea nausea/vomiting), cytopenias, and minimal ototoxicity (limited to tinnitus) at the dose range tested. The addition of DFMO to the nitrosourea-based PCV regimen in this phase III study demonstrated no additional benefit in glioblastoma patients, underscoring the resistance of glioblastoma multiforme tumors to alkylating agents. For patients with anaplastic (intermediate grade) gliomas, in which the previously demonstrated benefit of post-radiation chemotherapy is more substantial, the evaluation of DFMO-PCV vs. PCV is still ongoing and hopefully will yield more encouraging results.
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PMID:Phase III randomized study of postradiotherapy chemotherapy with alpha-difluoromethylornithine-procarbazine, N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosurea, vincristine (DFMO-PCV) versus PCV for glioblastoma multiforme. 1105 Dec 33

Deep-seated astrocytomas within the basal ganglia and the thalamus are considered unfavourable for microsurgical removal since the circumferential neighbourhood of critical structures limits radical resection. On closer assessment, the thalamus has a unique configuration within the basal ganglia. Its tetrahedric shape has 3 free surfaces and only the ventrolateral border is in contact with vital and critical functional structures, e.g. the subthalamic nuclei and the internal capsule. The purpose of the present study was to investigate the feasibility of maximum microsurgical removal in a series of intrinsic thalamic astrocytomas. 14 patients with intrathalamic astrocytomas grades I to 4 as diagnosed by previous stereotactic biopsy or intra-operative frozen section were selected for maximum microsurgical removal. The infratentorial supracerebellar approach from the contralateral side was used for 4 limited neoplasms of the pulvinar. For the other 10 larger and more extensive processes a parieto-occipital transventricular approach was chosen. Final histology gave the result of astrocytoma grade 1 or 2 in 4 patients, and of astrocytoma grade 3 or 4 in 10 patients. Postoperative MRI confirmed reduction of the tumor mass by 80 to 100% in 11 of 14 cases. Regional ancillary radiotherapy with 60 Gy was administered postoperatively for astrocytomas grades 3 and 4. Two patients operated on via the posterior transventricular approach had new postoperative partial hemianopia. Five of the 14 patients finally needed a ventriculo-peritoneal shunt. During the follow-up time of 6 to 52 months, tumor progression/recurrence was observed in 6 of the 10 high grade and none of the low grade neoplasms. The present pilot series demonstrates the feasibility of the microsurgical concept. Comparison with other treatment modalities, such as brachytherapy, requires future consideration.
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PMID:Thalamic astrocytomas: surgical anatomy and results of a pilot series using maximum microsurgical removal. 1121 25

Pharmacyclics is developing Gd-Tex (gadolinium texaphyrin) as a radiosensitizer for the potential treatment of various cancers including brain metastases and primary brain tumors, pancreatic tumors, lung tumors and pediatric cancers [196711], [348919]. The compound entered phase III pivotal trials for brain metastases in September 1998 [323929]. Phase I clinical trials for the treatment of primary brain tumors and pancreatic cancer have been initiated while several trials in other cancer types are in the planning stages [367716]. In September 1998, Pharmacyclics announced the initiation of a pivotal phase III trial for the treatment of patients with brain metastases. This multicenter trial originally included 30 sites in the US, Canada and Europe, and was expected to enroll 425 patients. The FDA agreed that this trial qualified for Fast Track review if efficacy end-points are met [301265]. By October 2000, nearly all 450 patients in 50 sites had been completed [375959], [387023]. In September 2000, Pharmacyclics and the National Cancer Institute (NCI) initiated two phase I trials of Gd-Tex. The first was to determine the safety of two different dosing regimens of the drug during preoperative radiotherapy after induction chemotherapy in patients with stage IIA non-small cell lung cancer (NSCLC). The second would examine the use of Gd-Tex in combination with stereotactic Gamma Knife radiosurgery in patients with primary brain tumors known as glioblastoma multiforme [381561]. A phase Ib/II trial, for brain metastases, was conducted in America and France, and involved over 100 patients. At the ASCO 1998 meeting, interim tumor response data were presented for 37 patients. The overall tumor response rate (complete plus partial response rate) was 73%. Furthermore, MRI scanning confirmed that Gd-Tex accumulated selectively in tumors [287459]. Full results were announced in October 1998 at the American Society of Therapeutic Radiology and Oncology. Following ten daily injections followed by whole brain radiation, 77.7% of patients demonstrated a tumor response defined as greater than 50% reduction in tumor volume. Gd-Tex was well tolerated, and liver enzyme elevation was the dose-limiting effect, which was reversible. Death due to tumor progression was seen in 15% of the Gd-Tex group as opposed to 35% in the control group [302872]. In November 1999, Pharmacyclics commenced a phase I trial of Gd-Tex injection, sponsored by the NCI, for treating children with intrinsic pontine glioma. The goals of the phase I dose-ranging study were to determine the Gd-Tex dose and administration schedule that can be safely administered with radiation and to evaluate the localization of Gd-Tex in affected tumors using MRI [348035]. In March 1997 the Decision Network of the NCI voted to sponsor additional clinical indications including adult and pediatric brain tumors, as well as cancers involving the lung, head & neck, pancreas and prostrate. Two phase I trials of Gd-Tex for the treatment of primary brain tumors commenced in August 1998 under a CRADA with the NCI [237538], [295592], [348919]. Pharmacyclics is collaborating with the NCI under a CRADA in phase I trials in primary brain tumors and pancreatic tumors [323929], [323952], [346596]. Analysts expected a filing to occur by the end of 1999 or early 2000, with sales in 2001 [303186].
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PMID:Gd-Tex Pharmacyclics Inc. 1124 9

9-Aminocamptothecin (9-AC) was administered as a 72-h i.v. infusion every 2 weeks to a total of 99 adults with high-grade astrocytomas. Fifty-one patients with newly diagnosed glioblastoma multiforme received 9-AC treatment prior to radiation therapy and 48 patients with high-grade astrocytomas were treated at the time of tumor recurrence. Upon entrance into these research protocols, all patients had measurable disease that was evaluated on a monthly basis with volumetric CT or MRI scans. A partial response was defined by > or =50% reduction in the contrast enhancing volume on stable or decreasing doses of glucocorticoids. The study specified that all apparent responders would have central review of their radiologic studies and histopathology. The initial patients treated with 9-AC were also receiving anticonvulsants and were noted to have minimal myelosuppression with this chemotherapy. Thus, 9-AC doses were escalated from the previously reported maximum tolerated dose (MTD) of 850 microg/m2/24 h. We then established new MTDs for patients receiving enzyme-inducing anticonvulsants. We defined these MTDs to be 1,776 microg/m2/24 h for newly diagnosed, previously untreated patients and 1,611 microg/m2/24 h for patients with recurrent disease. Twenty-two patients with newly diagnosed glioblastoma multiforme received 9-AC at doses > or =1,776 microg/m2/24 h. Of these, 18 had evaluable disease on central review, and 0 of 18 (0%) demonstrated a partial or complete response. Twenty-one patients with recurrent high-grade astrocytomas were treated at 1,611 microg/m2/24 h; 20 had evaluable disease and 0 of 20 (0%) had a partial or complete response. Thus, the overall response rate in the 38 evaluable patients treated at the MTD was 0 of 38 (0%). Furthermore, of the 51 evaluable patients who were treated at doses less than the MTD, only one partial response was observed, yielding an overall response rate of 2%. Evidence of drug failure was rapid with tumor progression in one-half of patients after 2 drug cycles. 9-AC lacks evidence of substantial activity in patients with newly diagnosed or recurrent high-grade astrocytomas.
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PMID:Lack of efficacy of 9-aminocamptothecin in adults with newly diagnosed glioblastoma multiforme and recurrent high-grade astrocytoma. NABTT CNS Consortium. 1130 51

This 6-month-old Caucasian boy presented with a 10-day history of lethargy, obtundation, inability to hold his head up and mild torticollis. MRI and CT scans showed a large solid and cystic mass involving the right temporal, parietal and occipital lobes, pineal, superior pons, mesencephalon and posterior right thalamus. He underwent craniotomy initially for a partial tumor resection with an intraoperative diagnosis of desmoplastic astrocytoma. With immunohistochemistry and special stains the diagnosis of desmoplastic infantile ganglioglioma (DIG) was made. A near total resection was performed a week after initial resection.The patient then was treated with chemotherapy. Two months later an MRI showed tumor growth. Following additional aggressive chemotherapy, an MRI at 5 months post-resection indicated further tumor progression. This case illustrates that some DIGs may behave more aggressively than typical WHO grade I lesions.
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PMID:December 2000: 6 month old boy with 2 week history of progressive lethargy. 1130 3

We report on a young woman who was treated by stereotactic radiotherapy for recurrence of an initially resected low-grade astrocytoma. MRI follow-up examination 7 months after radiotherapy showed a gadolinium-DTPA-enhancing mass lesion indicative of high-grade tumor progression. This assumption was also supported by positron emission tomography with [2-18F]fluoro-2-deoxy-D-glucose (FDG-PET). In contrast, proton MR spectroscopy (1H-MRS) indicated radiation necrosis, which was confirmed histopathologically in surgical specimens. Subsequent follow-up examinations up to 19 months after surgery showed no evidence of tumor recurrence.
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PMID:Differentiation of radiation necrosis from tumor progression using proton magnetic resonance spectroscopy. 1194 75


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