We fetch to your notice a new website where you can buy kamagra jelly australia at a low cost with fast delivery to Australia.


Canadian recommendationsfor the treatment ofglioblastoma multiforme W.P. Mason MD, R. Del Maestro MD,D. Eisenstat MD, P. Forsyth MD, D. Fulton MD,N. Laperrière MD, D. Macdonald MD,J. Perry MD, and B. Thiessen MD for theCanadian GBM RecommendationsCommittee* ABSTRACT
The recommended clinical target volume should beidentified with gadolinium-enhanced T1-weighted Recommendation 1
MRI, with a margin in the order of 2–3 cm. Targetvolumes should be determined based on a postsurgi- Management of patients with glioblastoma multi- cal planning MRI. A shorter course of radiation may forme (GBM) should be highly individualized and be considered for older patients with poor perfor- should take a multidisciplinary approach involving neuro-oncology, neurosurgery, radiation oncology,and pathology, to optimize treatment outcomes. Pa- Recommendation 6
tients and caregivers should be kept informed of theprogress of treatment at every stage.
During RT, temozolomide 75 mg/m2 should be admin-istered concurrently for the full duration of radio- Recommendation 2
therapy, typically 42 days. Temozolomide should begiven approximately 1 hour before radiation therapy, Sufficient tissue should be obtained during surgery and at the same time on the days that no radiotherapy for cytogenetic analysis and, whenever feasible, for Recommendation 7
Recommendation 3
Adjuvant temozolomide 150 mg/m2, in a 5/28-day Surgery is an integral part of the treatment plan, to schedule, is recommended for cycle 1, followed by establish a histopathologic diagnosis and to achieve 5 cycles if well tolerated. Additional cycles may be safe, maximal, and feasible tumour resection, which considered in partial responders. The dose should be may improve clinical signs and symptoms.
increased to 200 mg/m2 at cycle 2 if well tolerated.
Weekly monitoring of blood count is advised during Recommendation 4
chemoradiation therapy in patients with a low white The preoperative imaging modality of choice is mag- blood cell count. Pneumocystis carinii pneumonia has netic resonance imaging (MRI) with gadolinium as the been reported, and prophylaxis should be considered.
contrast agent. Other imaging modalities, such aspositron emission tomography with [18F]-fluoro- Recommendation 8
deoxy-D-glucose, may also be considered in selected For patients with stable clinical symptoms during cases. Postoperative imaging (MRI or computed to- combined radiotherapy and temozolomide, comple- mography) is recommended within 72 hours of sur- tion of 3 cycles of adjuvant therapy is generally ad- gery to evaluate the extent of resection.
vised before a decision is made about whether tocontinue treatment, because pseudo-progression is a Recommendation 5
common phenomenon during this time. The recom- Postoperative external-beam radiotherapy is recom- mended duration of therapy is 6 months. A longer mended as standard therapy for patients with GBM.
duration may be considered in patients who show The recommended dose is 60 Gy in 2-Gy fractions.
berta Cancer Registry database of GBM patients diag-nosed between 1975 and 1991 reported that only 1.8% Selected patients with recurrent GBM may be candi- survived at least 3 years 9. A decade later, an analy- dates for repeat resection when the situation appears sis by the Glioma Outcomes Project of cases diag- favourable based on an assessment of individual pa- nosed between 1997 and 2001 reported a median tient factors such as medical history, functional sta- survival of 40.9 weeks for newly-diagnosed patients tus, and location of the tumour. Entry into a clinical . An analysis of the Surveillance, Epide- trial is recommended for patients with recurrent miology, and End Results database found no signifi- cant improvement in the GBM survival rate after the1980s 1.
Recommendation 10
The principal reasons for poor outcome in GBM The optimal chemotherapeutic strategy for patients are the high rates of recurrence and of resistance to who progress following concurrent chemoradiation chemotherapy. Choucair et al. estimated that more has not been determined. Therapeutic and clinical– than 90% of gliomas recur, typically at the site of the molecular studies with quality of life outcomes are original tumour 11. Numerous chemotherapy regi- mens, administered either before RT or adjuvantly,have been investigated, but they have had little im- KEY WORDS
pact on patient outcomes 12–16. Prognosis is affectedby the histologic features of the tumour, patient age, Brain tumour, glioblastoma, radiotherapy, chemo- Standard treatment for GBM was significantly al- tered following the results of a large phase III trial 1. INTRODUCTION
conducted by the European Organization for the Re-search and Treatment of Cancer (EORTC) and the Na- Glioblastoma multiforme (GBM) is a World Health tional Cancer Institute of Canada 19. The EORTC–NCIC Organization grade IV astrocytoma and the most com- CE3 trial randomized 573 newly-diagnosed glioblas- mon and aggressive primary brain tumour 1. In North toma patients to RT alone (2 Gy, 5/7-day schedule for America, the estimated age-adjusted incidence of GBM 6 weeks, 60 Gy total), or to RT in combination with is 3.0 per 100,000 population 1. It occurs more com- the oral alkylating agent temozolomide. The temo- monly in males (male:female ratio of approximately zolomide dose was 75 mg/m2 daily during RT, fol- 3:2) and is typically diagnosed in patients in their lowed by adjuvant temozolomide 150–200 mg/m2 daily in a 5/28-day schedule for 6 cycles. With the The preoperative imaging modality of choice is RT–temozolomide combination, 2-year survival was gadolinium-enhanced magnetic resonance imaging 26.5% as compared with 10.4% with RT alone. Me- (MRI). Although contrast-enhanced MRI may indicate dian survival was 12.1 months and 14.6 months re- a discrete border, GBM tumours are characterized by spectively. As a result, concurrent RT and extensive microvascular infiltration and rapid prolif- temozolomide, followed by 6 monthly cycles of ad- eration. Based on distinct pathogenetic features, at juvant temozolomide, became the new standard of least two subtypes of GBM can be defined. Primary care for patients newly diagnosed with GBM.
(de novo) glioblastoma is more common in older pa- However, numerous questions remain about how tients (mean age: 55 years) 2 and typically harbours to identify patients who will be more likely to respond overexpression or mutation of epidermal growth fac- to treatment and how to optimize a multimodal ap- tor receptor, genetic losses on chromosome 10, p16 proach to patient management. The recommendations or p19 alterations, or loss of the tumour suppressor that follow were developed by a multidisciplinary protein phosphatase and tensin homologue 3–6. Sec- panel of Canadian neuro-oncologists, neurosurgeons, ondary glioblastoma develops more slowly from a and radiation oncologists—based on level 1 evidence lower-grade tumour and typically occurs in younger where possible—as a guide to optimizing the man- patients (≤45 years). Genetic alterations may include TP53 mutation or overexpression of platelet-derivedgrowth factor receptor α 7.
Although imaging techniques and multimodal treatment strategies have improved since the mid- 2.1 General Principles
1980s, little impact has been made on the ultimateprognosis of GBM. A population-based cohort study Recommendation 1 Management of patients with
of all Ontario Cancer Registry cases of GBM identi- GBM should be highly individualized and should take fied between 1982 and 1994 found that the median a multidisciplinary approach involving neuro-oncol- survival of patients receiving radiotherapy (RT) and ogy, neurosurgery, radiation oncology, and pathol- surgery was 11 months; median survival with sur- ogy, to optimize treatment outcomes. The care path gery alone was 3 months 8. An analysis of the Al- of GBM is complex and requires the cooperation and CURRENT ONCOLOGY—VOLUME 14, NUMBER 3 integration of services from multiple health care spe- treated patients with promoter methylation. In the cialties and institutions so as to avoid unacceptable subgroup of patients with promoter methylation, 2-year survival was 46% in the RT–temozolomide All surgeries should be presented at a weekly group as compared with 22.7% in patients treated brain tumour conference, with the neurosurgeon, ra- with RT alone (Table I). In the subgroup of patients diation oncologist, and neuro-oncologist present. Ide- without promoter methylation, median survival was ally, for each case, the multidisciplinary team should only marginally superior with combined RT–temozol- review the patient’s clinical status, neuroimaging, and omide than with RT alone (12.7 months vs.
histopathologic findings to determine the optimal 11.8 months); 2-year survival was 13.8% as compared It is recommended that the neurosurgeon inform Temozolomide is a recommended treatment for the patient of the diagnosis. Patients and caregivers newly-diagnosed GBM and for recurrent high-grade should be kept informed of the progress of treatment gliomas. Although MGMT methylation status appears at every stage. Patients should receive a brain tumour to be a prognostic factor for increased survival and information package to help them understand GBM and possibly for better response to temozolomide, a pro- the treatment options, and to better inform their deci- spective study is required before promoter hyper- sion-making. Patient consent should be obtained for methylation can be used as a guide to treatment Recommendation 2 The molecular genetic determi-
2.2 Pathology
nation of brain tumours is becoming increasinglyimportant, enabling more accurate diagnosis and Specific, unique genetic changes are common in as- prognosis. Sufficient tissue should be obtained dur- trocytic tumours. An estimated one half of grades II– ing surgery for cytogenetic analysis and, whenever III infiltrating astrocytomas have detectable mutations feasible, for tumour banking. The preliminary pathol- in the TP53 tumour suppressor gene 20. Loss of het- ogy report should be available within 48 hours post erozygosity on chromosomes 1p and 19q is usually surgery; the final report should be completed within associated with oligodendroglioma, but sometimes occurs in oligoastrocytomas. Loss of heterozygosityis associated with increased sensitivity to pro- 2.3 Surgery
carbazine–lomustine–vincristine chemotherapy 21. Inthat regard, two EORTC phase II trials reported that first- Recommendation 3 Surgery is an integral part of the
or second-line temozolomide produced a high re- treatment plan, to establish a histopathologic diag- sponse rate in patients with recurrent or progressive nosis and to achieve safe maximal tumour resection, oligoastrocytoma or oligodendroglioma 22,23; re- which may improve clinical signs and symptoms.
sponse was associated with 1p and 19q loss 24. Glio- A gross total resection, if achievable, is advised blastoma multiforme is more chemoresistant, and in any patients with a primary or recurrent malignant genetic markers do not appear to have comparable glial tumour if the surgery can be performed without prognostic significance 25. Of particular importance, significant risk to the patient. Simpson et al. analysed however, is O6-methylguanine DNA methyltransferase data from 645 GBM patients in three prospective Ra- (MGMT), a repair protein that removes methyl adducts diation Therapy Oncology Group trials 33. Surgery and transfers them to an internal cysteine residue 26.
consisted of total resection (19%), partial resection Because the O6 position is one of the targets of alky- (64%), or biopsy only (17%). Median survival was lating chemotherapeutic agents, MGMT activity en-hances tumour resistance by repairing cytoxicdamage. Conversely, tumour sensitivity is enhanced Effect of methylation status of methylguanine DNA if MGMT is silenced through hypermethylation of the methyltransferase (MGMT) promoter on progression-free survival CpG islands in the promoter region 27–29.
(PFS) and overall survival (OS) in patients receiving radiotherapy A number of studies have indicated that MGMT plus temozolomide (TMZ) versus radiotherapy (RT) alone a promoter methylation is predictive of a good responseto alkylating agents such as 1,3-bis(2-chloroethyl)- Following the phase III study of combined RT and tem- ozolomide 19, Hegi et al. analyzed the methylation status of 206 evaluable patients 32. In 92 tumours (44.7%), MGMT promoter methylation was detectable. Median survival was 18.2 months in pa- tients with promoter methylation as compared with 12.2 months in those without methylation, and me-dian survival was 21.7 months in RT–temozolomide- CURRENT ONCOLOGY—VOLUME 14, NUMBER 3 11.3 months for total resection, 10.4 months for par- ficacy, but are associated with significant toxicity 39.
tial resection, and 6.6 months for biopsy.
Most studies were reported decades ago, but a recentphase II trial evaluated BCNU 80 mg/m2 on days 1–3 Recommendation 4 The preoperative imaging mo-
every 8 weeks (maximum 6 cycles) in 40 patients dality of choice is MRI with gadolinium as the con- with recurrent GBM who had undergone surgery and trast agent. Other imaging modalities, such as positron . The median time to progression was 13 weeks; emission tomography with [18F]-fluoro-deoxy-D-glu- the 6-month progression-free survival (PFS) was cose, may also be considered in selected cases 34.
17.5%. Significant side effects included reversible Postoperative imaging (MRI or computed tomography) hematologic toxicities and chronic hepatic and pul- is recommended within 72 hours of surgery to evalu- Recommendation 6 During RT, temozolomide
2.4 Radiotherapy
75 mg/m2 should be administered concurrently for42 days 35. Temozolomide should be given approxi- The use of adjuvant external-beam RT is well estab- mately 1 hour before RT, and at the same time on the lished in the postoperative treatment of GBM. A pooled days when no RT is scheduled (weekends).
analysis of six randomized trials by Cancer Care Whether the clinical benefit of this combination Ontario reported a significant survival benefit is attributable in part to the radiosensitizing effects favouring postoperative RT as compared with no RT of temozolomide is unclear. To date, four in vitro stud- (risk ratio: 0.81) 35,36. Overall, median survival is ies have suggested a radiosensitizing effect with tem- approximately 36–48 weeks with adjuvant RT as com- ozolomide for some cancer cell lines 52–55, but pared with 14–22 weeks with surgery alone 37–39.
External-beam RT is generally administered over Recommendation 7 Adjuvant temozolomide
5–6 weeks, delivering a total dose of 50–60 Gy in 150 mg/m2, in 5/28-day schedule, is recommended 1.8- to 2.0-Gy fractions 40. Doses above 60 Gy and for cycle 1, followed by 5 cycles if well tolerated.
boost RT do not appear to influence survival 40,41.
Additional cycles may be considered in partial re- Alternative forms of fractionation have been in- sponders or in those with continuing radiologic im- vestigated. Accelerated fractionation delivers stan- provement. The dose should be increased to dard fraction sizes more frequently (for example, 2 200 mg/m2 at cycle 2 if well tolerated. Weekly moni- or 3 times daily) to reduce the overall treatment toring of blood count is advised during chemoradi- time. Several studies have reported no increased sur- ation therapy in patients with a low white blood cell v i v a l , a l t h o u g h n o i n c r e a s e d t o x i c i t y w a s count. Pneumocystis carinii pneumonia has been re- found 42–44. This approach may be an option for se- ported, and prophylaxis should be considered 56.
lected patients (such as the elderly), but additionalstudy is needed.
Recommendation 8 For patients with stable clinical
Hyperfractionation, which delivers a higher total symptoms during RT–temozolomide, completion of radiation dose in a larger number of smaller fractions, 3 cycles of adjuvant therapy is generally advised be- showed no improvement in time to tumour progres- fore a decision is made about whether to continue treatment. In the first few weeks or months follow- Radiotherapy should be initiated within 4 weeks ing completion of RT, MRI is not reliable to assess true progression. Evidence of progression outside the RTfield is indicative of true progression. A longer dura- Recommendation 5 Postoperative external-beam RT
tion may be considered in patients who show con- is recommended as standard therapy for patients with GBM. The recommended dose is 60 Gy in 2-Gy frac-tions 35,36. The recommended clinical target volume 2.6 Recurrent GBM
should be identified with gadolinium-enhancedT1-weighted MRI, with a margin in the order of 2– Recommendation 9 Selected patients with recurrent
3 cm, given that most recurrences will occur within GBM may be candidates for repeat resection when the a few centimetres of the tumour mass 47,48. Target situation appears favourable based on an assessment volumes should be determined based on a postsurgi- of individual patient factors such as medical history, cal planning MRI. A shorter course of radiation may functional status, and location of the tumour 57,58.
be considered for older patients with poor perfor- Entry into a clinical trial is recommended for patients 2.5 Chemotherapy
Recommendation 10 The optimal chemotherapeu-
tic strategy for patients who progress following
Glioblastoma multiforme has been viewed as a concurrent chemoradiation has not been determined.
chemoresistant tumour, and the nitrosoureas, the tra- Therapeutic and clinical-molecular studies with qual- ditional mainstays of treatment, have had modest ef- CURRENT ONCOLOGY—VOLUME 14, NUMBER 3 For patients not receiving chemotherapy at the Overall survival was 11.2 months. The most common time of progression, re-challenge with temozolomide grade 3–4 toxicity was granulocytopenia, which oc- to deplete MGMT might be attempted, but clinical data Some preliminary data suggest that novel dose- 3. CONCLUSIONS
intense schedules may provide some benefit. Khanet al. reported a 6-month PFS of 19% with temozolo- Surgery followed by RT still represents the primary mide 75 mg/m2 in a 42/70-day schedule 59. In a small approach to the treatment of GBM. The addition of phase II study by Wick et al., the 6-month PFS was temozolomide chemotherapy to the standard of care 48% with temozolomide 150 mg/m2 administered in has significantly increased the proportion of patients a 7-day on / 7-day off schedule 60. Although the find- who survive more than 2 years. However, additional ings are promising, additional phase II studies are re- progress still needs to be made, because almost one quired before the foregoing dosing regimens can be half of GBM patients will not survive the first year after surgery. Additional research is needed to build A number of chemotherapeutic agents, includ- on recent clinical gains and to focus on new drug ing nitrosoureas, carboplatin, etoposide, irinotecan, combinations or therapies that could potentially fur- and imatinib 61–64, have been used as salvage therapy ther improve outcomes in patients with GBM.
either alone or in combination. Additional trials witha variety of agents are underway, but preliminary re- 4. ACKNOWLEDGMENT
sults from single-agent studies have been disappoint-ing. Table II summarizes phase II studies in GBM.
Funding for the Canadian GBM Recommendations For patients who progress on temozolomide, com- Committee meeting was provided by Schering bination therapy may be possible; several recent trials have evaluated various temozolomide combinations(Table II). For example, the efficacy of bolus temo- 5. REFERENCES
zolomide 130 mg/m2 followed by 70 mg/m2 every12 hours for 5 days, plus cisplatin 75 mg/m2, was 1. Deorah S, Lynch CF, Sibenaller ZA, Ryken TCR. Trends in brain cancer incidence and survival in the United States: Sur- the 49 evaluable patients, 1 patient achieved a com- veillance, Epidemiology, and End Results program, 1973 to plete response, and 9 achieved partial responses. The 2001. Neurosurg Focus 2006;20:1–7.
6-month PFS was 34%; the 12-month PFS was 4%.
2. DeAngelis LM. Brain tumours. N Engl J Med 2001;344: Phase II studies in recurrent glioblastoma multiforme TMZ 150–200 mg/m2 daily, 5/28-day schedule vs. PCB 125–150 mg/m2, 28/56-day schedule + marimastat 50 mg, days 8–28 × 2 cycles + cis-retinoic acid 100 mg/m2, 21/28-day schedule TMZ 130 mg/m2 bolus, TMZ 70 mg/m2 every 12 hours × 5 days BCNU 80 mg/m2, days 1–3 every 8 weeks × 6 cycles maximum BCNU 200 mg/m2, day 1 of every 6-week cycle + thalidomide 800 mg daily (maximum 1200 mg) + irinotecan 175 mg/m2 weekly × 4 weeks in every 6 weeks (maximum 8 cycles) Paclitaxel 175 mg/m2 day 1 + topotecan 1.0 mg/m2 days 1–5 Gefitinib 500 mg daily; dose escalation to 750–1000 mg cis-Retinoic acid 100 mg/m2 daily, 21/28-day schedule Temsirolimus (mTor inhibitor) 250 mg weekly Trial suspended because of significant hemotoxicity.
PFS = progression-free survival; TMZ = temozolomide; PCB = procarbazine; BCNU = 1,3-bis(2-chloroethyl)-1-nitrosourea; NA = not available; PCV = procarbazine–lomustine–vincristine.
CURRENT ONCOLOGY—VOLUME 14, NUMBER 3 3. Watanabe K, Tachibana O, Sata K, Yonekawa Y, Kleihues P, 17. Scott JN, Rewcastle NB, Brasher PMA, et al. Which glioblas- Ohgaki H. Overexpression of the EGF receptor and p53 muta- toma multiforme patient will become a long-term survivor? A tions are mutually exclusive in the evolution of primary and population-based study. Ann Neurol 1999;46:183–8.
secondary glioblastomas. Brain Pathol 1996;6:217–24.
18. Perry A, Jenkins RB, O’Fallon JR, et al. Clinicopathologic 4. Biernat W, Tohma Y, Yonekawa Y, Kleihues P, Ohgaki H. Al- study of 85 similarly treated patients with anaplastic astro- terations of cell cycle regulatory genes in primary (de novo) cytic tumors: an analysis of DNA content (ploidy), cellular and secondary glioblastomas. Acta Neuropathol (Berl) 1997; proliferation, and p53 expression. Cancer 1999;86:672–83.
19. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy 5. Roversi G, Pfundt R, Moroni RF, et al. Identification of novel plus concomitant and adjuvant temozolomide for glioblastoma.
genomic markers related to progression to glioblastoma N Engl J Med 2005;352:987–96.
through genomic profiling of 25 primary glioma cell lines.
20. Maintz D, Fiedler K, Koopmann J, et al. Molecular genetic evidence for subtypes of oligoastrocytomas. J Neuropathol 6. Hill C, Hunter SB, Brat DJ. Genetic markers in glioblastoma: Exp Neurol 1997;56:1098–104.
prognostic significance and future therapeutic implications.
21. Eoli M, Bissola L, Bruzzone MG, et al. Reclassification of Adv Anat Pathol 2003;10:212–17.
oligoastrocytomas by loss of heterozygosity studies. Int J 7. Hermanson M, Funa K, Koopmann J, et al. Association of loss of heterozygosity on chromosome 17p with high platelet- 22. van den Bent MJ, Taphoorn MJ, Brandes AA, et al. Phase II derived growth factor alpha receptor expression in human study of first-line chemotherapy with temozolomide in recur- malignant gliomas. Cancer Res 1996;56:164–71.
rent oligodendroglioma: the European Organisation of Re- 8. Paszat L, Laperriere N, Groome P, Schulze K, Mackillop W, search and Treatment of Cancer Brain Tumour Group study Holowaty E. A population-based study of glioblastoma 26971. J Clin Oncol 2003;21:2525–8.
multiforme. Int J Radiat Oncol Biol Phys 2001;51:100–7.
23. van den Bent MJ, Chinot O, Boogerd W, et al. Second-line 9. Scott JN, Rewcastle NB, Brasher PM, et al. Long-term glio- chemotherapy with temozolomide in recurrent oligodendro- blastoma multiforme survivors: a population-based study. Can glioma after PCV (procarbazine, lomustine and vincristine) che- J Neurol Sci 1998;25:197–201.
motherapy: EORTC Brain Tumour Group study 26972. Ann 10. Laws ER, Parney IF, Huang W, et al. Survival following sur- gery and prognostic factors for recently diagnosed malignant 24. Triebels VH, Taphoorn MJ, Brandes AA, et al. Salvage PCV glioma: data from the Glioma Outcomes Project. J Neurosurg chemotherapy for temozolomide-resistant oligodendrogliomas.
11. Choucair AK, Levin VA, Gutin PH, et al. Development of 25. Houillier C, Lejeune J, Benouaich–Amiel A, et al. Prognostic multiple lesions during radiation therapy and chemotherapy impact of molecular markers in a series of 220 primary glio- in patients with gliomas. J Neurosurg 1986;65:654–8.
blastomas. Cancer 2006;106:2218–23.
12. Green SB, Byar DP, Walker MD, et al. Comparisons of 26. Pegg AE, Dolan ME, Moschel RC. Structure, function, and carmustine, procarbazine, and high-dose methylprednisolone inhibition of O6-alkylguanine-DNA alkyltransferase. Prog as additions to surgery and radiotherapy for the treatment of Nucleic Acid Res Mol Biol 1995;51:167–223.
malignant glioma. Cancer Treat Rep 1983;67:121–32.
27. Costello JF, Futscher BW, Kroes RA, Pieper RO. Methyla- 13. Chang CH, Horton J, Schoenfeld D, et al. Comparison of post- tion-related chromatin structure is associated with exclusion operative radiotherapy and combined postoperative radio- of transcription factors from and suppressed expression of the therapy and chemotherapy in the multidisciplinary manage- O-6-methylguanine DNA methyltransferase gene in human ment of malignant gliomas: a joint Radiation Therapy Oncol- glioma cell lines. Mol Cell Biol 1994;14:6515–21.
ogy Group and Eastern Cooperative Oncology Group study.
28. Watts GS, Pieper RO, Costello JF, et al. Methylation of dis- crete regions of the O6-methylguanine DNA methyltransferase 14. Shapiro WR, Green SB, Burger PC, et al. Randomized trial of (MGMT) CpG island is associated with heterochromatinization three chemotherapy regimens and two radiotherapy regimens of the MGMT transcription start site and silencing of the gene.
and two radiotherapy regimens in postoperative treatment of Mol Cell Biol 1997;17:5612–19.
malignant glioma: Brain Tumor Cooperative Group trial 8001.
29. Danam RP, Qian XC, Howell SR, Brent TP. Methylation of selected CpGs in the human O6-methylguanine-DNA 15. Grossman SA, O’Neill A, Grunnet M, et al. Phase III study methyltransferase promoter region as a marker of gene silenc- comparing three cycles of infusional carmustine and cisplatin ing. Mol Carcinog 1999;24:85–9.
followed by radiation therapy with radiation therapy and con- 30. Esteller M, Garcia–Foncillas J, Andion E, et al. Inactivation current carmustine in patients with newly diagnosed suprat- of the DNA-repair gene MGMT and the clinical response of glio- entorial glioblastoma multiforme: Eastern Cooperative Oncol- mas to alkylating agents. N Engl J Med 2000;343:1350–4.
ogy Group Trial 2394. J Clin Oncol 2003;21:1485–91.
31. Esteller M, Gaidano G, Goodman SN, et al. Hypermethylation 16. Deutsch M, Green SB, Strike TA, et al. Results of a random- of the DNA repair gene O(6)-methylguanine DNA methyl- ized trial comparing BCNU plus radiotherapy, streptozotocin plus transferase and survival of patients with diffuse large B-cell radiotherapy, BCNU plus hyperfractionated radiotherapy, and lymphoma. J Natl Cancer Inst 2002;94:26–32.
BCNU following misonidazole plus radiotherapy in the postop- 32. Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing erative treatment of malignant glioma. Int J Radiat Oncol Biol and benefit from temozolomide in glioblastoma. N Engl J Med CURRENT ONCOLOGY—VOLUME 14, NUMBER 3 radiotherapy, BCNU plus hyperfractionated radiotherapy, and 33. Simpson JR, Horton J, Scott C, et al. Influence of location and BCNU following misonidazole plus radiotherapy in the postop- extent of surgical resection on survival of patients with glio- erative treatment of malignant glioma. Int J Radiat Oncol Biol blastoma multiforme: results of three consecutive Radiation Therapy Oncology Group (RTOG) clinical trials. Int J Radiat 47. Gaspar LE, Fisher BJ, Macdonald DR, et al. Supratentorial Oncol Biol Phys 1993;26:239–44.
malignant glioma: patterns of recurrence and implications for 34. De Witte O, Levivier M, Violon P, et al. Prognostic value external beam local treatment. Int J Radiat Oncol Biol Phys positron emission tomography with [18F]fluoro-2-deoxy-D-glu- cose in the low-grade glioma. Neurosurgery 1996;39:476–477.
48. Lee SW, Fraass BA, Marsh LH, et al. Patterns of failure fol- 35. Perry J, Zuraw L, for the Neuro-Oncology Disease Site Group.
lowing high-dose 3-D conformal radiotherapy for high-grade Adjuvant systemic chemotherapy, following surgery and ex- astrocytomas: a quantitative dosimetric study. Int J Radiat ternal beam radiotherapy, for adults with newly diagnosed Oncol Biol Phys 1999;43:79–88.
malignant glioma: a clinical practice guideline. Evidence-based 49. Keime–Guibert F, Chinot O, Taillandier F, et al. Phase 3 study series 9-2. Section 1. Toronto: Cancer Care Ontario; March comparing radiotherapy with supportive care in older patients 2004, updated May 2006. [Available online at: www.
with newly diagnosed anaplastic astrocytomas (AA) or glio- cancercare.on.ca/index_neurooncologyGuidelines.htm; cited blastoma multiforme (GBM): an ANOCEF group trial (abstract).
36. Laperriere N, Zuraw L, Cairncross G, Cancer Care Ontario 50. Roa W, Brasher PM, Bauman G, et al. Abbreviated course of Practice Guidelines Initiative Neuro-Oncology Disease Site radiation therapy in older patients with glioblastoma Group. Radiotherapy for newly diagnosed malignant glioma multiforme: a prospective randomized clinical trial. J Clin in adults: a systematic review. Radiother Oncol 2002;64: 51. Brandes AA, Tosoni A, Amista P, et al. How effective is BCNU 37. Kristiansen K, Hagen S, Kollevold T, et al. Combined modal- in recurrent glioblastoma in the modern era? A phase II trial.
ity therapy of operated astrocytomas grade III and IV. Confir- mation of the value of post-operative irradiation and lack of 52. Wedge SR, Porteous JK, Glaser MG, et al. In vitro evaluation potentiation of bleomycin on survival time: a prospective of temozolomide combined with X-irradiation. Anticancer multicenter trial of the Scandinavian Glioblastoma Study Group. Cancer 1981;47:649–52.
53. van Rijn J, Heimans JJ, van den Berg J, et al. Survival of human 38. Kelly KA, Kirkwood JM, Kapp DS. Glioblastoma multiforme: glioma cells treated with various combination of temozolo- pathology, natural history and treatment. Cancer Treat Rev mide and X-rays. Int J Radiat Oncol Biol Phys 2000;47: 39. Walker MD, Alexander E Jr, Hunt WE, et al. Evaluation of 54. Trog D, Moenkemann H, Haertel N, et al. Expression of ABC- BCNU and/or radiotherapy in the treatment of anaplastic glio- 1 transporter is elevated in human glioma cells under irradia- mas: a cooperative clinical trial. J Neurosurg 1978;49:333–43.
tion and temozolomide treatment. Amino Acids 2005;28: 40. Laperriere NJ, Bernstein M. Radiotherapy for brain tumors.
CA Cancer J Clin 1994;44:96–108.
55. Wick W, Wick A, Schulz JB, et al. Prevention of irradiation- 41. Souhami L, Seiferheld W, Brachman D, et al. Randomized induced glioma cell invasion by temozolomide involves comparison of stereotactic radiosurgery followed by conven- caspase 3 activity and cleavage of focal adhesion kinase. Can- tional radiotherapy with carmustine to conventional radio- therapy with carmustine for patients with glioblastoma 56. Ammirati M, Galicich JH, Arbit E, Liao Y. Reoperation in the multiforme: report of Radiation Therapy Oncology Group 93- treatment of recurrent intracranial malignant gliomas. Neuro- 05 protocol. Int J Radiat Oncol Biol Phys 2004;60:853–60.
42. Simpson WJ, Platts ME. Fractionation study in the treatment 57. Su YB, Sohn S, Krown SE, et al. Selective CD4+ lymphopenia of glioblastoma multiforme. Int J Radiat Oncol Biol Phys 1976; in melanoma patients treated with temozolomide: a toxicity with therapeutic implications. J Clin Oncol 2004;22:610–16.
43. Keim H, Potthoff PC, Schmidt K, Schiebusch M, Neiss A, 58. Barker FG 2nd, Chang SM, Gutin PH, et al. Survival and func- Trott KR. Survival and quality of life after continuous accel- tional status after resection of recurrent glioblastoma erated radiotherapy of glioblastoma. Radiother Oncol 1987; multiforme. Neurosurgery 1998;42:709–20.
59. Khan RB, Raizer JJ, Malkin MG, Bazylewicz KA, Abrey LE.
44. Horiot JC, van den Bogaert W, Ang KK, et al. European Or- A phase II study of extended low-dose temozolomide in re- ganization for Research on Treatment of Cancer trials using current malignant gliomas. Neuro-oncol 2002;4:39–43.
radiotherapy with multiple fractions per day. Front Radiat Ther 60. Wick W, Steinbach JP, Kuker WM, Dichgans J, Bamberg M, Weller M. One week on/one week off: a novel active regimen 45. Fulton DS, Urtasun RC, Scott–Brown I, et al. Increasing ra- of temozolomide for recurrent glioblastoma. Neurology 2004; diation dose intensity using hyperfractionation in patients with malignant glioma. Final report of a prospective phase I-II dose 61. Brandes AA, Tosoni A, Basso U, et al. Second-line chemo- response study. J Neurooncol 1992;14:63–72.
therapy with irinotecan plus carmustine in glioblastoma 46. Deutsch M, Green SB, Strike TA, et al. Results of a random- recurrent or progressive after first-line temozolomide chemo- ized trial comparing BCNU plus radiotherapy, streptozotocin plus therapy: a phase II study of the Gruppo Italiano Cooperativo CURRENT ONCOLOGY—VOLUME 14, NUMBER 3 di Neuro-Oncologia (GICNO). J Clin Oncol 2004;22:4779–86.
74. Rich JN, Reardon DA, Peery T, et al. Phase II trial of gefitinib 62. Franceschi E, Cavallo G, Scopece L, et al. Phase II trial of in recurrent glioblastoma. J Clin Oncol 2004;22:133–42.
carboplatin and etoposide for patients with recurrent high-grade 75. See SJ, Levin VA, Yung WK, Hess KR, Groves MD. 13-cis- glioma. Br J Cancer 2004;91:1038–44.
Retinoic acid in the treatment of recurrent glioblastoma 63. Reardon DA, Quinn JA, Vredenburgh J, et al. Phase II trial of multiforme. Neuro-oncol 2004;6:253–8.
irinotecan plus celecoxib in adults with recurrent malignant 76. Chang SM, Wen P, Cloughesy T, et al. Phase II study of CCI- glioma. Cancer 2005;103:329–38.
779 in patients with recurrent glioblastoma multiforme. Invest 64. Reardon DA, Egorin MJ, Quinn JA, et al. Phase II study of imatinib mesylate plus hydroxyurea in adults with recurrentglioblastoma multiforme. J Clin Oncol 2005;23:9359–68.
65. Yung WK, Albright RE, Olson J, et al. A phase II study of temozolomide vs. procarbazine in patients with glioblastomamultiforme at first relapse. Br J Cancer 2000;83:588–93.
66. Groves MD, Puduvalli VK, Hess KR, et al. Phase II trial of Correspondence to: Warren P. Mason, Princess Mar-
temozolomide plus the matrix metalloproteinase inhibitor, garet Hospital, 610 University Avenue, Suite 18-717, marimastat, in recurrent and progressive glioblastoma multiforme. J Clin Oncol 2002;20:1383–8.
E-mail: [email protected]
67. Jaeckle KA, Hess KR, Yung WK, et al. Phase II evaluation of temozolomide and 13-cis-retinoic acid for the treatment of recurrent and progressive malignant glioma: a North Ameri- Chair—Warren P. Mason, Department of Medi- can Brain Tumor Consortium study. J Clin Oncol 2003;21: cine, University of Toronto, and Princess Margaret Hospital, Toronto, Ontario; Members— 68. Brandes AA, Basso U, Reni M, et al. First-line chemotherapy Rolando Del Maestro, Department of Neurology with cisplatin plus fractionated temozolomide in recurrent glio- and Neurosurgery and Department of Oncology, blastoma multiforme: a phase II study of the Gruppo Italiano McGill University, and Brain Tumor Research Cooperativo di Neuro-Oncologia. J Clin Oncol 2004;22: Centre, Montreal Neurological Institute and Hos- pital, Montreal, Quebec; David Eisenstat, 69. Brandes AA, Ermani M, Turazzi S, et al. Procarbazine and CancerCare Manitoba, Manitoba Institute of Cell high-dose tamoxifen as a second-line regimen in recurrent high-grade gliomas: a phase II study. J Clin Oncol 1999;17: Anatomy, and Ophthalmology, University of Manitoba, Winnipeg, Manitoba; Peter Forsyth, 70. Kappelle AC, Postma TJ, Taphoorn MJ, et al. PCV chemo- Clark Smith Integrative Brain Tumor Research therapy for recurrent glioblastoma multiforme. Neurology Center, Calgary, Alberta; Dorcas Fulton, Depart- ment of Medicine, Cross Cancer Institute, and 71. Fine HA, Wen PY, Maher EA, et al. Phase II trial of thalido- University of Alberta, Edmonton, Alberta; mide and carmustine for patients with recurrent high-grade Normand Laperriere, Department of Radiation gliomas. J Clin Oncol 2003;21:2299–304.
Oncology, University of Toronto, and Princess 72. Brandes AA, Tosoni A, Basso U, et al. Second-line chemo- Margaret Hospital, Toronto, Ontario; David therapy with irinotecan plus carmustine in glioblastoma re- Macdonald, Department of Medicine, London current or progressive after first-line temozolomide chemo- Regional Cancer Center, and University of West- therapy: a phase II study of the Gruppo Italiano Cooperativo ern Ontario, London, Ontario; James Perry, Crolla di Neuro-Oncologia (GICNO). J Clin Oncol 2004;22:4779–86.
Family Brain Tumour Research Centre, Univer- 73. Pipas JM, Meyer LP, Rhodes CH, et al. A phase II trial of sity of Toronto, Toronto, Ontario; and Brian paclitaxel and topotecan with filgrastim in patients with re- Thiessen, British Columbia Cancer Agency, and current or refractory glioblastoma multiforme or anaplastic University of British Columbia, Vancouver, Brit- astrocytoma. J Neurooncol 2005;71:301–5.

Source: http://www.ynnn.dk/filer/neuroonkologi/straaleglioblastom.pdf




“I had to win. not One Woman’s Cancer Answer only was my life at an interview by Jeff Gordon www.eatwithoutheat.com stake, but I needed to find help for So just what did you learn eaten the All-American Diet–a diet that, in my about cancer? opinion, that greatly contributes to today’s others as well!” Two major conclusions Great American

Copyright © 2010-2014 Medical Science