Radiosurgery for Malignant Glioma

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    Int. J. Radiation Oncology Biol. Phys., Vol. 63, No. 1,pp. 4755, 2005

    Copyright 2005 American Society for TherapeuticRadiology and Oncology. Published by Elsevier Inc.

    Evidence-based Review of the Role of

    Radiosurgery for Malignant Glioma

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    Background

    y A doseresponse relationship has been reported in earlierstudies of postoperative radiation therapy.

    y Majority (90% or more) of recurrences occur within 2 cm of

    the enhancing edge of the original tumour.y Above mentioned points makes a background to give high

    dose radiation at a specific area in the form of single fractionor fractionated radiosurgery for patients with newly

    diagnosed or recurrent malignant glioma.

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    Purpose :-

    y To systematically review the evidence for theuse of stereotactic radiosurgery or stereotactic

    fractionated radiation therapy in adult patientswith malignant glioma

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    Methodology

    y Expert panel selection.

    y Process overview

    MEDLINE (19902004 June Week 2),CANCERLIT(1990

    2003), CINAHL (19902004 June Week 2),EMBASE

    (19902004Week 25), and the Cochrane library(2004issue 2) databases were searched using OVID. The

    proceedings of the ASTROAmerican Society ofTherapeutic Radiology and Oncology (19972004), and the

    ESTRO European Society of Therapeutic Radiology and

    Oncology (19972003) were also searched

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    Methodology

    Formulation of key clinical question

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    RADIOSURGERY FOR NEWLY

    DIAGNOSED MALIGNANT GLIOMA

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    y Key clinical question #1: In patients treated with surgery

    and conventional radiation,does radiosurgeryboost (either before or after conventional radiation)improve survival as compared to no radiosurgery boostin patients diagnosed with malignant glioma?

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    Evidence

    y

    One RCT -There was no advantage with radiosurgery boostin terms of survival

    y Five prospective studies- Three of the five studies reported no

    difference in survival as compared with historic expectation.

    y Seven retrospective studies- Many reported survival outcomes ofradiosurgery boost after radiotherapy to be superior as compared

    with historical controls, such analyses may be prone to selection bias

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    Conclusion

    y However, many of the retrospective or cohort studies thatindicated an improved survival benefit in patients treatedwith radiosurgery boost.

    y

    There is Level I evidence that the use of radiosurgeryboost followed by external beam radiotherapy andcarmustine (BCNU) does not confer benefit with respectto overall survival, quality of life, or patterns of failure ascompared with external beam radiotherapy and BCNU

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    y Key clinical question #2:Does the use of radiosurgery

    boost improve quality of life or symptom control in

    patients with newly diagnosed malignant glioma?

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    Evidence

    y

    One RCT Reported no improvement in quality of life

    y Five prospective studies- Two of the five studies commented onKPS score change with radio surgery boost.

    y Six retrospective studies- Only study commented on mean KPS

    outcomes

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    Conclusion

    y Data on these prospective and retrospective studies are consideredinsufficient to support a quality of life or symptom control benefitwith the use of radiosurgery boost in patients with newly diagnosedmalignant glioma.

    y Furthermore, the confounding factor of steroid use and its impacton changes in quality of life or symptom control make

    interpretation of these outcomes in these studies difficult

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    y Key clinical question #3:Does the use of radiosurgery

    boost improve brain control/tumor response in patients

    with newly diagnosed malignant glioma?

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    Evidence

    y

    One RCTThe duration of glioblastoma response to therapy wasnot reported.

    y Three prospective studies- Two of the studies included only

    Grade 4 astrocytoma , And remaining one study included somepatients with Grade 3 astrocytoma and some patients with mixedglioma histology

    y Four retrospective studies- In one of the study , none of thepatient had complete response to radiosurgery boost. And rest threereported on very high local and marginal failures (80%).

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    Conclusion

    y Thus there remains lack of high quality evidence that radiosurgeryboost improves brain control or tumor response in patients withnewly diagnosed malignant glioma.

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    y Key clinical question #4:Does the use of radiosurgery

    boost increases toxicity in patients with newlydiagnosed malignant glioma?

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    Evidence

    y

    One RCTThere were four Grade 3 late toxicities in the radiosurgery arm compared with none in the external beam and BCNUarm

    y

    Five prospective studies- Rreports range from no significant acuteor late toxicity to brain necrosis in 2 of 37 patients in one seriesand 4 of 29 patients in other study.

    y Four retrospective studies- Most of studies report on a fewpatients developing significant edema, or radiation necrosis.

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    Conclusion

    y Thus there is Level I-III evidence that the addition of radiosurgeryboost is associated with an increased risk of toxicity ranging fromsignificant edema to radiation necrosis

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    Salvage Therapy for Recurrent or

    Progressive Malignant Glioma

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    y Key clinical question #1:Does radiosurgery assalvage for recurrent or progressive malignant

    glioma improve survival?

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    Evidence

    y

    None RCT

    y 2 prospective studies- For glioblastoma patients, only 15% werealive and progression-free at 6 months.

    y Four retrospective studies- Median survival for these patientswere reported as being better than historical controls for Grade 3astrocytoma patients, but worse for Grade 4 astrocytoma patients.

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    Conclusion

    y Thus there is insufficient evidence to support a survival benefit inthe use of radiosurgery at the time of progressive or recurrentmalignant glioma as compared with competing strategies of

    management such as debulking surgery, chemotherapy, or bestsupportive care.

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    y Key clinical question #2: Does the use of radiosurgery

    as salvage for recurrent or progressive malignant gliomaimprove quality of life or symptom control?

    y None of the studies reported on quality of life or symptomcontrol outcomes

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    y Key clinical question #3:Does the use of radiosurgerysalvage improve brain control/tumor response inpatients with recurrent or progressive malignantglioma?

    y The results on brain control/tumor response have not beencompared with competing strategies such as debulking surgery,

    chemotherapy, or best supportive care.

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    y Key clinical question #4:Does the use of radiosurgery

    salvage increase toxicity in patients with recurrent orprogressive malignant glioma?

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    Evidence

    y None RCT

    y 2 prospective Studies- One study found 7/20 patients to havedeveloped early side effects from radiosurgery

    y Four retrospective studies-. Nineteen of 86 patients in one studydeveloped radiation necrosis.

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    Conclusion In nut shell

    y There is Level II-3 evidence that the use of radiosurgery at the timeof recurrence may improve survival and brain control in selectedpatients but at a cost of possible toxicity. In the absence of higher

    quality evidence, this intervention may be considered an option forselected patients.

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    STEREOTACTIC FRACTIONATED

    RADIATION

    THERAPY FOR MALIGNANT GLIOMA

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    y Key clinical question #1:Does the use of fractionatedstereotactic radiation therapy for newly diagnosed

    malignant glioma improve survival?

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    Evidence

    y None RCT

    y 2 prospective studies- One study found no difference in time toprogression or median survival from historical controls..

    y Four retrospective-These data were compared to a historical groupand were reported as being superior for the fractionated stereotacticradiation therapy group of patients..

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    Conclusion

    y Because of heterogeneity, small sample size, and lack of randomizeddata, it is not possible to discern whether a survival benefit existswith the use of fractionated stereotactic radiation therapy for newly

    diagnosed malignant glioma patients.

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    y Key clinical question #2:Does the use of Fractionatedstereotactic radiation therapy for newly diagnosed

    malignant glioma improve quality of life or symptomcontrol?

    y None of the studies reported on quality of life or symptom control

    outcomes.

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    y Key clinical question #3:Does the use of fractionatedstereotactic radiation therapy for newly diagnosed

    malignant glioma improve local brain control or braintumor response?

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    Evidence

    y None RCT

    y 1 prospective studies-no significant difference as compared withhistorical controls treated with conventional external beam

    radiotherapyy 2 retrospective studies

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    y Key clinical question #4:Does the use of fractionated

    stereotactic radiation therapy for newly diagnosed

    malignant glioma increase toxicity?

    y Radiation necrosis in 1 of 17 patients in one study and 4 of

    12 patients having radionecrosis in other study.

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    Conclusion in nut shell

    y Because of the heterogeneity of studies, small sample sizes, and lack

    of randomized data, there is insufficient evidence that fractionatedstereotactic radiation therapy for newly diagnosed malignant glioma

    confers benefit in terms of survival, quality of life, symptomcontrol, or local brain control/brain tumor response as comparedwith conventional management consisting of surgery followed byexternal beam radiotherapy with or without chemotherapy.

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    AT THE TIME OF RECURRENCE OR

    PROGRESSION

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    y Key clinical question #1:Does the use of fractionated

    stereotactic radiation therapy for recurrent orprogressive malignant glioma improve survival?

    y There were 3 prospective and 2 retrospective study butMedian survival was not statistically different in thosepatients receiving radiosurgery salvage as compared

    with fractionated stereotactic radiation therapy forsalvage.

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    y Key clinical question #2:Does the use offractionated stereotactic radiation therapy forrecurrent or progressive malignant glioma improve

    quality of life or symptom control?

    y 0nly one study which showed Seventy-sevenpercent of patients treated with fractionated

    stereotactic radiation therapy at recurrence hadimproved Barthel scores at 3 months, whereas 67%had improved Barthel indices at 6 months

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    y Key clinical question #3:Does the use of fractionatedstereotactic radiation therapy for recurrent or

    progressive malignant glioma improve brain controlor brain tumor response?

    y One study showed 7.1% treated with fractionatedstereotactic radiation therapy demonstrated stable

    disease. No patient demonstrated complete or partialresponse

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    y Key clinical question #4: Does the use of fractionatedstereotactic radiation therapy for recurrent orprogressive malignant glioma result in toxicity?

    y One study reported on 4 of 22 patients developing neurologicdeterioration due to radiation toxicity. Three of 25 patients in otherseries underwent reoperations for radiation necrosis or progression.

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    Conclusion in nut shell

    y Because of the heterogeneity of studies, small sample sizes, and lack

    of randomized data, there is insufficient evidence that fractionatedstereotactic radiation therapy for recurrent or progressive malignant

    glioma confers benefit in terms of survival, quality of life, symptomcontrol, or local brain control/brain tumor response as comparedwith competing strategies such as debulking surgery, chemotherapy,or best supportive care

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