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PubMed1995

Survival predictors in advanced non-small cell lung cancer.

The authors studied the influence on survival of 21 clinical, anatomical, haematological and biochemical factors evaluated, at diagnosis, of 411 patients (pts) with advanced Non Small Cell Lung Cancer (NSCLC) followed in our department between 1984 and 1990. Most of the patients were male (347--84.4%) and only 64 (15.6%) were females. Median age was 62 years, but was slightly higher in females. Only 34 patients were aged under 45 years. Squamous cell carcinoma (215 pts--52%) and adenocarcinoma (152 pts--37%) were the most frequent histologic types. Performance status was poor--only 103 (25%) continued active; 120 (29%) spent at least half of the time in bed; 188 (46%) were severely limited. After staging, 179 (44%) presented locally advanced disease (stage IIIB) and 232 (56%) metastatic dissemination (stage IV). Therapy was defined by the oncologic group according to individual characteristics and based on clinical grounds. Anti-neoplastic therapy was performed in 225 (55%), chemotherapy alone in 121 (30%), radiation therapy alone in 67 (16%), and sequential combined treatment (chemotherapy and thoracic radiation) in 37 (9%). Until 1987, the main chemotherapy regimen was MACC (Metrotrexate + Adriamycine + Cyclophosphamide + Lomustin), afterwards VP(M) (Cisplatin + Vimblastin + Mitomycine). Radiation therapy was performed using Co60, 2 Gy/day, 5 days a week, for 4 weeks (approximately 45 Gy total). The response rate was poor--four complete responses (2%), 42 (19%) partial responses. The overall median survival was 4.3 months and only 5% of patients were alive after 18 months of follow up. Prognostic importance of each characteristic studied was initially done by unifactorial analysis, followed by multifactorial analysis according to two methods: Cox proportional hazards model and recursive partitioning amalgamation--RECPAM. Regardless of the method used, the main determinants of survival were found to be performance status (Zubrod), weight loss and serum albumin. Other factors such as the staging (presence or absence of metastasis), lymphocytes, lactic dehydrogenase, and hoarseness were also significant. It is noteworthy that age and histological type were irrelevant; sex and hoarseness only proved important when integrated within a multifactorial model. The overall prognostic evaluation and therapeutic decision of advanced NSCLC patients could be improved by combining the prognostic value of TNM with that of performance status, weight loss and serum albumin. These prognostic guidelines must be taken into account when designing new clinical trials.

Adenocarcinoma↗
PubMed1988

Immunopotentiating activities of a low molecular weight lipopeptide, RP 56 142--studies in infectious models.

RP 56 142, N2-[N-(N-lauroyl-L-alanyl)-gamma-D glutamyl] L,L-2,6-diaminopimelamic acid belongs to a family of immunomodulating lipopeptides. Its structure is directly derived from that of lauroyltetrapeptide RP 40 639 which is a mixture of two stereoisomers, one of which (with D,D-2,6 diaminopimelamic acid) is totally devoid of in vivo activity. RP 56 142 displayed potent protective activities against bacterial infections such as K. pneumoniae, L. monocytogenes or S. typhimurium (at doses ranging between 0.03 and 100 mg/kg s.c., i.p., i.v.). In combined treatment protocols, suboptimal doses of RP 56 142 given preventively (day-1) or curatively (day 0 + 4h) significantly protected mice receiving antibiotics at doses which were ineffective when administered by themselves. Given s.c. 1 or 2 days before infectious challenge, RP 56 142 was able to normalize and even enhance significantly the resistance of mice previously immunocompromised by lomustine, 5-fluorouracile or hydrocortisone. These results correlated with the stimulation of the clearance of a virulent Salmonella typhimurium strain and with an important production of colony-stimulating factor in RP 56 142-treated mice.

Adjuvants, Immunologic↗
PubMed1990

Validation of clinical predictive value of in vitro colorimetric chemosensitivity assay in head and neck cancer.

For chemosensitivity testing, a rapid in vitro colorimetric method (MTT assay) was used. Eleven head and neck cancer cell lines were investigated to distinguish five known active agents from five compounds inactive in phase II studies. Evaluation of the reliability of the assay for assessing drug sensitivity in this tumor cell population was done by correlating the in vitro results with reported in vivo response data. Methotrexate and cisplatin (clinically active) and vindesine and doxorubicin (less active clinically) were recognized in vitro as active and correlated well with clinical experience. Bleomycin (clinically active) was ineffective against some cell lines. The in vitro findings for the clinically inactive drugs (deoxyazacytidine, lomustine, and carmustine) also corresponded. Amsacrine and etoposide, contrary to clinical experience, showed activity in vitro. Further comparison of MTT assay results with clinical data is warranted and essential before its use in large-scale drug screening studies.

Antineoplastic Agents↗
PubMed1992

Enhancement of alkylating agent activity in vitro by PD 128763, a potent poly(ADP-ribose) synthetase inhibitor.

The ability of DNA repair inhibitors to potentiate alkylating agent cytotoxicity was explored with PD 128763, a dihydroisoquinolinone known to effectively inhibit poly(ADP-ribose) synthetase. The cytotoxic activity of streptozotocin in L1210 leukemia cells was maximally potentiated (7-fold decrease in IC50) under conditions of 24 hr exposure to PD 128763 following treatment with the alkylating agent for 1 hr. Similar treatment conditions resulted in a much greater effect (36-fold enhancement in activity) for the 2-nitroimidazole RSU 1069. In contrast, 3-aminobenzamide was only weakly effective at enhancing activity of either streptozotocin or RSU 1069 (2-3 fold potentiation). However, PD 128763 was ineffective at potentiating the cytotoxicity of the bifunctional alkylating agents carmustine (BCNU) and lomustine (CCNU). Our results are consistent with a role for (poly-ADP) ribosylation in the repair of monofunctional alkylating agent damage. This study supports further exploration of the combination of PD 128763 and RSU 1069 as a potentially useful chemotherapeutic regimen.

Alkylating Agents↗
PubMed1994

Patterns of recurrence of glioblastoma multiforme after external irradiation followed by implant boost.

PURPOSE: To study patterns of recurrence in patients with focal primary glioblastoma treated on Northern California Oncology Group protocol 6G-82-2 including surgery, focal external beam radiotherapy (59.4-60 Gy) with oral hydroxyurea followed by temporary brain implant with high-activity iodine-125 sources (50 Gy), and six cycles of chemotherapy with procarbazine, lomustine, and vincristine. METHODS AND MATERIALS: Serial brain imaging scans were available for review in 25 of 34 patients with glioblastoma who underwent brain implant boost. Of 381 scans performed between the date of diagnosis and the date of death or last follow-up, 362 (95%) were re-reviewed. Disease progression was scored as local (within 2 cm of the implant site), separate within the brain parenchyma (> or = 2 cm from the implant site), subependymal, or systemic. Both initial and subsequent failures were scored. RESULTS: Three patients are 5-year survivors, without evidence of disease, at 267, 292, and 308 weeks. Of the 22 initial sites of failure, 17 (77%) were local, three (14%) were separate brain lesions (one of which was due in retrospect to multicentric disease at diagnosis), one (5%) subependymal, and one (5%) systemic. Five patients with local failure later had other sites of failure, including a separate brain lesion in 1, subependymal spread in 3, and both in 1. One patient with separate brain failure later had local progression and then subependymal spread. CONCLUSION: Although there was a significant risk of separate brain lesions or subependymal spread over time, local tumor progression was the predominant pattern of failure.

Adult↗
PubMed1995

Combination of computerized morphonuclear and multivariate analyses to characterize in vitro the antineoplastic effect of alkylating agents.

The influence of 13 anticancer alkylating agents on cell proliferation, cell cycle parameters, and morphonuclear characteristics was monitored in vitro on three neoplastic cell lines. This monitoring was carried out by means of the digital cell image analysis of Feulgen-stained nuclei. This computer-assisted microscope analysis of chromatin texture made it possible to assess 15 morphonuclear parameters. These 15 parameters were submitted to multivariate analyses, that is, principal-components analyses followed by the canonical transformation of the data. The 13 alkylating agents included four nitrogen mustards (chlormethine, chlorambucil, melphalan, and cyclophosphamide), two nitrosoureas (carmustine and lomustine), two platinum analogues (cisplatine and carboplatine), two ethyleneimine derivatives (thiotepa and investigational PE1001), one antibiotic (mitomycin C), one alkylsulfonate (busulfan), and one triazene (dacarbazine). The mouse MXT mammary and the human J82 and T24 bladder tumor cell lines were used in this study. The results show that these alkylating agents induced specific modifications to the chromatin pattern according to the subclass to which they belong. In other words, the multivariate statistical analyses of the 15 parameters made it possible to identify, at least partly, distinct subclasses of alkylating agents according to their mechanisms of action. As a validation of the methodology, the results also show that most of the alkylating agents induced an increase in the percentage of cells in the G2 phase, while some sometimes induced an increase in the percentage of cells in the S phase of the cell cycle.

Adenocarcinoma↗
PubMed2004

Concurrent chemotherapy and reduced-dose cranial spinal irradiation followed by conformal posterior fossa tumor bed boost for average-risk medulloblastoma: efficacy and patterns of failure.

PURPOSE: To review the efficacy and patterns of failure in average-risk medulloblastoma patients treated with concurrent chemotherapy and reduced-dose cranial spinal irradiation and a conformal tumor bed boost. METHODS AND MATERIALS: Thirty-three patients with average risk (defined as < or =1.5 cm(2) of residual tumor after resection, age >3 years, and no involvement of the cerebrospinal fluid or spine [M0]) medulloblastoma were diagnosed at our institution between January 1994 and December 2001. They were enrolled in an institutional pilot protocol consisting of concurrent chemotherapy (vincristine), reduced-dose cranial spinal irradiation (2340 cGy), a conformal primary tumor bed boost (3240 cGy), followed by eight cycles of chemotherapy (vincristine, cisplatin, and lomustine or cyclophosphamide). The median age at diagnosis of the 33 patients was 7 years (range, 3-21 years). The male/female patient ratio was 2.4:1. The median follow-up of the entire group was 37 months (range, 6-96 months), and the median follow-up of the survivors was 44 months (range, 10-96 months). RESULTS: The 5-year estimated disease-free survival rate, as determined by Kaplan-Meier plots, was 86% (+/-12.6%, 95% confidence interval). The 5-year estimated disease-free posterior fossa control and primary tumor bed control rates were both 94% (+/-8.2%, 95% confidence interval). The patterns of failure included 2 patients with distant central nervous system failure only, 1 patient who developed local primary tumor bed failure, posterior fossa failure, and diffuse leptomeningeal spread simultaneously, and 1 patient with failure in the high-dose, primary tumor bed field. No patient experienced isolated posterior fossa failure outside the high-dose boost region. CONCLUSION: The treatment of average-risk medulloblastoma with chemotherapy, reduced-dose cranial spinal irradiation, and a conformal tumor bed boost results in survival rates and local control rates comparable to those in contemporary studies. A reduction in the amount of posterior fossa treated to the high dose is possible. These results need to be corroborated in a large, cooperative group study.

Adolescent↗
PubMed2004

Combined treatment modality for anaplastic oligodendroglioma and oligoastrocytoma: a 10-year update of a phase II study.

PURPOSE: To provide updated outcome data (10 years) of a Phase II study of combined surgery, postoperative radiotherapy, and adjuvant chemotherapy in patients with anaplastic oligodendroglioma and oligoastrocytoma. METHODS AND MATERIALS: In 23 adult patients, surgery, postoperative radiotherapy (60 Gy in 30 daily fractions within 6 weeks), and adjuvant modified chemotherapy (procarbazine 60 mg/m(2) on Days 1-14, lomustine 100 mg/m(2) on Day 1, and vincristine 1.4 mg/m(2) [maximum 2 mg] on Days 1 and 8) were administered every 6 weeks for up to six cycles or until progression occurred. RESULTS: The median follow-up was 116 months for all patients. The median survival time was 118 months, and the 5-year and 10-year survival rate was 57% and 47%, respectively. The median time to tumor progression was 78 months, with a 5-year and 10-year progression-free survival rate of 52% and 39%, respectively. Gender, age, Karnofsky performance status, location, and histologic type did not influence survival. Patients with tumors 4 cm (p = 0.0470), as did those with total tumor resection compared with those with subtotal tumor resection or biopsy only (p = 0.0024). Gender, Karnofsky performance status, location, and histologic type did not influence progression-free survival, but younger age (p = 0.0389), smaller tumor size (p = 0.0357), and more radical surgery (p = 0.0033) correlated positively with it. Acute high-grade (Grade 3 or worse) chemotherapy-related toxicity was mainly hematologic, with 3 patients (13%) experiencing acute Grade 4 toxicity. CONCLUSION: The results of this 10-year update confirmed that the trimodality approach is effective in patients with anaplastic oligodendroglioma and oligoastrocytoma.

Astrocytoma↗
PubMed1999

Recent advances in the brain targeting of neuropharmaceuticals by chemical delivery systems.

Brain-targeted chemical delivery systems represent a general and systematic method that can provide localized and sustained release for a variety of therapeutic agents including neuropeptides. By using a sequential metabolism approach, they exploit the specific trafficking properties of the blood-brain barrier and provide site-specific or site-enhanced delivery. After a brief description of the design principles, the present article reviews a number of specific delivery examples (zidovudine, ganciclovir, lomustine benzylpenicillin, estradiol, enkephalin, TRH, kyotorphin), together with representative synthetic routes, physicochemical properties, metabolic pathways, and pharmacological data. A reevaluated correlation for more than 60 drugs between previously published in vivo cerebrovascular permeability data and octanol/water partition coefficients is also included since it may be useful in characterizing the properties of the blood-brain barrier, including active transport by P-glycoprotein.

Journal Article↗
PubMedDate not supplied

Glioblastoma multiforme metastatic to the neck.

Glioblastoma multiforme, a rapidly growing intracranial neoplasm, rarely metastasizes unless operated upon, and even after surgical exposure metastasis is uncommon unless the patient is a long-term survivor. The most likely site of metastasis is the cervical lymph nodes. A patient developed a rapidly expanding cervical metastasis a year after surgery and irradiation for the primary. The 6-cm neck mass responded dramatically to radiation therapy and lomustine. The patient is clinically without evidence of progression of disease 20 months after the initial diagnosis, and there is no palpable recurrence in the neck. It is recommended that the patient who has a cervical mass and a history of surgically treated glioblastoma multiforme undergo a careful otolaryngologic examination prior to open biopsy. In general, such a patient can be spared an extensive "unknown primary" evaluation before biopsy.

Adult↗
PubMed2002

Structure-based design of nitrosoureas containing tyrosine derivatives as potential antimelanoma agents.

Two new nitrosoureas (TNUs), containing tyrosine derivatives as carriers of nitrosourea cytotoxic group have been synthesised. The physicochemical properties such as half-life time (tau(0.5)), alkylating and carbamoylating activities were determined. The nitrosoureas showed a higher inhibiting effect on the DOPA-oxidase activity of mushroom tyrosinase than that of the antitumour drug N'-cyclohexyl-N-(2-chloroethyl)-N-nitrosourea (lomustine, CCNU). In vitro cytotoxic effects of newly synthesised tyrosine containing nitrosoureas have been studied and compared to those of CCNU. A higher cytotoxicity to B16 melanoma cells than to YAC-1 and to lymphocytes was demonstrated for the tyrosine containing nitrosoureas in comparison with CCNU. Based on the results presented, we accept that a new trend for synthesis of more selective and less toxic nitrosourea derivatives as potential antimelanomic drugs might be developed.

Antineoplastic Agents↗
PubMed1998

Survival results from a phase I study of etanidazole (SR2508) and radiotherapy in patients with malignant glioma.

PURPOSE: To report the survival results from a previous Phase I study of etanidazole (ETA) and radiotherapy in patients with glioblastoma multiforme (GBM n = 50) or anaplastic astrocytoma (AA n = 19) and examine survival according to age, Karnofsky performance status (KPS), and implant status. PATIENTS AND METHODS: In a previous Phase I study, 70 previously untreated patients (median age 49) with malignant gliomas were accrued. One patient was excluded from analysis because pathology was unverifiable. All had KPS > or = 70. Prior to initiation of treatment, patients were stratified according to whether they were candidates for interstitial implantation. The implant patients (IMP n = 14) received accelerated fractionation radiotherapy (XRT) 2 Gy BID (6 hours apart) to 40 Gy in 2 weeks with ETA 2 gm/m2 x 6 doses, a 2 week break, and then interstitial implant for an additional 50 Gy (4-7 days) with a continuous infusion of ETA over 90-96 hours. There were 55 patients treated on two sequentially conducted non-implant arms. These patients started with accelerated fractionation XRT 2 Gy BID (6 hours apart) to 40 Gy in 2 weeks with ETA 2 gm/m2 x 4-5 doses/week. Non-IMP1 arm (n = 41) received a 2-week break before standard fractionated boost XRT of 2 Gy/day for 2 weeks to a total dose of 60 Gy with ETA. Non-IMP2 arm (n = 14) did not have the 2-week break. All patients had plasma pharmacokinetic monitoring of ETA. Subsequent follow-up study provided information regarding long-term survival status of this group of patients. The Phase I toxicity evaluation was conducted according to the RTOG toxicity scale and was found well tolerated in both groups. Overall actuarial survival was plotted for all patients, by histologic group, and by implant status. Subset analyses of GBM patients by age (< or = 49 or > 49 years), KPS (< or = 80 or > 80) and implant versus non-implant were also performed. RESULTS: Median survival of GBM patients was 1.1 years and that of anaplastic astrocytoma patients was 3.1 years (p = 0.0001). In GBM patients, KPS > 80, implanted patients, and age < or = 49 were factors found not to be associated with a statistically improved survival. CONCLUSION: The results of survival in this Phase I etanidazole study of patients with anaplastic astrocytoma are comparable to the results from other studies using bromodeoxyuridine, iododeoxyuridine, or procarbazine, lomustine (CCNU), and vincristine. The use of etanidazole with accelerated radiotherapy does not appear to improve survival in patients with glioblastoma multiforme compared to those treated with conventional therapies.

Adult↗
PubMed2001

Spin labelled nitrosoureas and triazenes and their non-labelled clinically used analogues--a comparative study on their physicochemical properties and antimelanomic effects.

Physicochemical properties, such as half life time (tau0.5), alkylating and carbamoylating activity and in vivo antimelanomic effects against B16 melanoma of spin labeled (containing nitroxyl free radical moiety) amino acid nitrosoureas, synthesized in our laboratory, have been studied and compared to those of the antitumor drug N'-cyclohexyl-N-(2-chloroethyl)-N-nitrosourea (lomustine, CCNU). We have shown that the introduction of amino acid moieties and the replacement of cyclohexylamine with nitroxyl moiety leads to a faster decomposition, higher alkylating, lower carbamoylating activity, better antimelanomic activity and lower general toxicity, when compared to those of CCNU. It was also established that spin labeled triazenes, previously synthesized by us, were more stable in phosphate saline than their nonlabeled analogue, 5-(3,3-dimethyltriazene-1-yl)-imidazole-4-carboxamide (dacarbazine, DTIC). A higher cytotoxicity to B16 melanoma cells than to YAC-1 and lymphocytes was demonstrated for all spin labeled triazenes, in comparison with DTIC. An assumption has been made to explain the lower general toxicity of the spin labeled nitrosoureas compared to that of CCNU. Based on the results presented, we accept that a new trend for synthesis of more selective and less toxic nitrosourea and triazene derivatives as potential antimelanomic drugs might be developed.

Animals↗
PubMed2001

Recurrent intracranial ependymoma in children: salvage therapy with oral etoposide.

Chronic oral VP-16 (etoposide) is a chemotherapy regimen with a wide application in oncology and documented efficacy against germ cell tumors, lymphomas, Kaposi's sarcoma, and primary brain tumors. This study was performed to assess the toxicity and activity of chronic oral etoposide in the management of children with recurrent intracranial nondisseminated ependymoma. Twelve children (median age of 8 years) with recurrent ependymoma who were refractory to surgery, radiotherapy, and chemotherapy (carboplatinum or the combination of procarbazine, lomustine, and vincristine) were treated with chronic oral etoposide (50 mg/m(2)/day). Treatment-related complications included the following: alopecia (10 children), diarrhea (6), weight loss (5), anemia (4), neutropenia (3), and thrombocytopenia (3). Three children required transfusion (two with packed red blood cells; two with platelets), and two children developed neutropenic fever. No treatment-related deaths occurred. Six children (50%) demonstrated either a radiographic response (two children, both with partial response) or stable disease (four children) with a median duration of response or stable disease of 7 months. In this small cohort of children with recurrent intracranial ependymoma, oral etoposide was well tolerated, produced modest toxicity, and had apparent activity.

Administration, Oral↗
PubMed1999

High-dose chemo/radiotherapy and autologous bone marrow or stem cell transplantation for poor-risk advanced-stage Hodgkin's disease during first partial or complete remission.

Complete remission rates of 70-90% can be achieved following combination chemotherapy for patients with advanced-stage Hodgkin's disease (HD). Patients who present with unfavorable poor prognostic factors, however, have a 5-year disease-free survival of only 40-50%. In an attempt to improve the prognosis of 20 patients with poor-risk advanced-stage HD, we evaluated the role of early high-dose therapy (HDT) and autologous bone marrow/stem cell transplantation (ASCT) during the first complete or partial remission (CR/PR). Patients were eligible for ASCT if they either achieved a PR (defined as > 50% regression) (six patients), or achieved a CR (14 patients) but had presented with three or more of the following unfavorable features: stage IV disease with bone marrow involvement or > or = 2 extranodal sites of involvement; bulky mass > 10 cm or bulky mediastinal mass > 1/3 of mediastina/thoracic ratio; B symptoms; and elevated serum lactate dehydrogenase (LDH) level. The study included 11 men (55%) and 9 women (45%). The median age was 37 years (range 20-57). Seventeen patients (85%) had stage IV disease; 14 (70%) had B symptoms; 13 (65%) had bulky mass > 10 cm; 14 (70%) had > or = 2 extra nodal sites involvement; and eight patients (40%) had elevated LDH levels. All patients were treated with standard four or 7-8 drug combination chemotherapy regimens until they achieved maximal response prior to ASCT with a median of six cycles (range 4-11). Six patients also received involved field radiotherapy to residual bulky mass > 5 cm or bony lesions before ASCT. The median time from diagnosis to ASCT was 8.6 months (range 5.5-18.9). Preparative regimens consisted of fractionated total body irradiation (FTBI) 1200 cGy in combination with etoposide 60 mg/kg and cyclophosphamide 100 mg/kg in all patients except one who had borderline pulmonary function and received lomustine 15 mg/kg instead of FTBI. All patients engrafted and there was no transplant-related mortality. One patient developed congestive cardiomyopathy at 4 years post-ASCT. All patients remain alive and in remission at a median follow-up of 42.8 months (range, 13.2-149.2). These preliminary results suggest that HDT and ASCT can be performed safely during first CR/PR in selected patients with advanced-stage HD who have an unfavorable prognosis. Further randomized studies comparing HDT and ASCT during first CR with conventional chemotherapy and ASCT at relapse in poor-risk advanced-stage HD should be conducted. The prognostic factors and risk groups described recently by an international prognostic study can be used to identify high-risk patients who may be candidates for more intensive therapy.

Adult↗
PubMed2001

PCV for oligodendroglial tumors: in search of prognostic factors for response and survival.

BACKGROUND: We report survival and pretreatment prognostic factors for survival and chemosensitivity in 53 oligodendrogliomas treated with PCV (procarbazine, lomustine and vincristine) chemotherapy. METHODS: A total of 53 patients with histologically proven oligodendroglioma, anaplastic oligodendroglioma or oligo-astrocytoma and treated with PCV were extracted from the London Regional Cancer Center database. A retrospective review was conducted to evaluate overall survival and pretreatment prognostic factors for survival and chemosensitivity. RESULTS: The median survival time from diagnosis was 123.6 months. The overall five- and ten-year survival rates were 72.7% and 52.7% respectively. Age <40, seizure as an initial symptom, absence of cognitive deficit and presence of a homogeneous hypodense lesion without contrast enhancement on the initial pretreatment CT scan were all factors independently associated with favorable outcome. The presence of increased cellularity, pleomorphism, mitosis, vascular proliferation and grading as an anaplastic lesion using these surrogates on pathological assessment, were all associated with an unfavorable outcome in univariable analysis. In multivariable analysis, only the anaplastic grading and presence of increased cellularity were significant determinants of unfavorable survival. The only factor adversely associated with chemosensitivity was the presence of a focal symptom at presentation. CONCLUSION: Overall survival is significantly longer in oligodendroglial lesions than in fibrillary astrocytic tumors. A two tier grading system using standard morphological features seems accurate in predicting outcome in these patients. The presence of a neoplastic astrocytic component does not seem to impact the outcome. No clinical, radiological or pathological factor could be identified to reliably predict chemotherapy response.

Adult↗
PubMed2003

Primary intraspinal primitive neuroectodermal tumor: report of two cases and review of the literature.

BACKGROUND: Primary intraspinal primitive neuroectodermal tumor (PNET) is a very rare tumor entity. The optimal therapeutic approach is not known yet. We report on two women with primary intraspinal PNETs and review the literature. We describe the typical course of the disease, compare our patients to the other 17 cases reported until today, and discuss therapeutic options. PATIENTS AND METHOD: Case A: In a 49-year-old woman with an intraspinal PNET at L2, laminectomy and a gross tumor removal was accomplished. Postoperative radiation was performed from T12 to L3 to a dose of 50.4 Gy. Subsequently she was treated with chemotherapy containing vincristine, cisplatinum and lomustine. Case B: A 29-year-old woman presented with intramedullary PNET lesions at T1-3 and T10-11. Due to the multifocal location, she received a primary craniospinal axis irradiation to a dose of 35.2 Gy plus a boost to the tumor region to a total dose of 53.2 Gy. RESULTS: Both patients developed multilocular intraspinal relapses with meningeosis neoplastica 17 and 6 months from radiation therapy and underwent palliative chemotherapy. Case A died 23 months, case B 17 months after primary diagnosis. CONCLUSION: Despite modern treatment with microsurgery, irradiation and chemotherapy in primary intraspinal PNETs, local relapse or dissemination in most cases lead to death within a few months. An improvement of treatment outcome can only be achieved by intensification through multidisciplinary treatment.

Adult↗
PubMed2004

Molecular genetic study of a metastatic oligodendroglioma.

Extracranial spread of neuroectodermal tumors is an unusual event, most frequently expected from glioblastomas and medulloblastomas. Single cases of metastatic oligodendrogliomas have been described, but no genetic data are reported. Oligodendrogliomas are characterized by distinct genetic alterations, i.e. loss of heterozygosity (LOH) of 1p and 19q; therefore, molecular genetic analysis of metastatic cases is of considerable interest. It may be instrumental in defining the distant tumor as metastatic oligodendroglioma and give clues to the genetic events associated with the highly malignant transformation. We present the case of a patient with multiple bone metastases from a cerebral oligodendroglioma. Oligodendroglioma grade II was the diagnosis both at original and second operation, performed 7 and 1 years before the extracranial dissemination. The extraneural spread presented before the local intracranial recurrence. The patient received procarbazine, lomustine, vincristine chemotherapy and radiotherapy after the second surgery. The computed tomography-guided biopsy of the bone lesions revealed tumor cells positive for GFAP, S-100 and Leu-7 and negative for cytokeratin, LCA and EMA. The genetic analysis of DNA from the original tumor, the bone metastasis and the autoptic brain tumor showed LOH of 1p; heterozygous deletion of CDKN2A/p 16 was detected as additional alteration in the metastasis and in the intracranial tumor at autopsy. TP53, MDM2 and CDKN2A/p14ARF genes were unchanged. Repeated brain surgery and extended survival may have acted as promoter of extraneural dissemination. Loss of CDKN2A most probably played an important role in the malignant progression: its involvement in metastatic potential remains to be clarified. Our data confirm that malignant transformation of oliogodendrogliomas may be undetected by histology and underscore the importance of genetic analysis. Coincidentally with intensive anticancer therapy, chemotherapy included, employed in patients with oligodendroglioma and the ensuing long survival, the frequency of metastatic oliogodendrogliomas may increase.

Biomarkers, Tumor↗