Summary of Recommendations

Summary of Recommendations

Low-Grade Glioma Guidelines (Edward Shaw, MD., task force chairman; published in Neurosurgical Focus in 1998)

Authors

Edward Shaw, M.D. (Chair, Radiation Oncology);,Mark Bernstein, M.D. (Co chair, Neurological Surgery); Lawrence Recht, M.D. (Co chair, Neurology); Stephen Ashway, M.D.; Mark Camel, M.D.; Robert Florin, M.D. (Advisor, AANS); Stephen Haines, M.D.; Brian O'Neill, M.D.; Jack Rock, M.D.; Jay Rosenberg, M.D. (Advisor, AAN); Mark Rosenblum, M.D.; Michael Shea, M.D.; Beverly Walters, M.D. (Advisor, AANS)

Question

What is the therapeutic effectiveness and practice parameters offered for adult patients who present with a seizure, are neurologically intact, and have an imaging study (CT or MR) that demonstrates a supratentorial nonoptic pathway, nonenhancing lesion that is consistent with a diffuse fibrillary astrocytoma, oligodendroglioma, or oligoastrocytoma.

Recommendations

Table 2 Recommendations

Management Issue / Evidence / Quality of Evidence / Summary Recommendation /
Biopsy (prior to active treatment) / There is no diagnostic test which is sufficient to act as a surrogate for the “gold standard” (tissue diagnosis, with 35% of patients in two studies having alternative diagnoses when presumed to have LGG on imaging / Class I / Standard
Biopsy (prior to observation alone) / Although there is evidence that MR or CT imaging cannot attain >65% positive predictive value, and therefore biopsy is the diagnostic test of choice, there is no evidence that it is harmful to patients to observe without biopsy / Class III / Option
Observation / In two series, patients were observed after tissue diagnosis had survival rates comparable to patients from other series receiving radiation therapy / Class III / Option
Resection / Seven series reported better survival for patients undergoing resection; in four, the survival differences were significant, survival was proportional to the degree of surgical resection / Class III / Option
Radiation Therapy / Two of six series reported significantly better survival for patients undergoing radiation therapy; in three of the other four series, survival was nonsignificant for nonradiated patients / Class III / Option

Newly Diagnosed Glioblastoma Guidelines (Jeffrey J. Olson, MD., task force chairman; published in Journal of Neuro-Oncology in 2008)

Neuroradiological Assessment

Authors

Srini Mukundan, Chad Holder, Jeffrey J. Olson

Question

What is the optimal method of imaging the lesions of patients suspected to have a newly diagnosed glioblastoma?

Recommendations

Level I:

Whenever possible, it is recommended that magnetic resonance imaging with the addition of gadolinium contrast enhancement be used because it provides information that may allow differentiation of glioblastoma from other intrinsic tumors and secondary tumors.

Level II:

Computerized tomography with the addition of contrast material may provide data allowing differentiation of glioblastoma from other intrinsic tumors and secondary tumors.

Level III:

The addition of proton magnetic resonance spectroscopy to standard anatomic magnetic resonance imaging provides details that may improve diagnostic accuracy for lesions of the brain, including brain tumors.

Utilization of perfusion magnetic resonance imaging with determination of mean regional blood volume may provide data that assists in separating the histologic characteristics of intrinsic tumors from one another.

Role of Cytoreductive Surgery

Authors

Timothy C. Ryken, Bruce Frankel, Terrance Julien, Jeffrey J. Olson

Question

What is the role of cytoreductive surgery in the initial management of the adult patient with malignant glioma?’

Recommendations

Level I

There is insufficient evidence to support a Level I Recommendation.

Level II

Based on the prospective data available and a general consensus in the retrospective data it is recommended that for newly diagnosed supratentorial malignant glioma in adults that the ‘‘maximal safe resection’’ be undertaken (i.e. the maximal cytoreductive procedure provided that postoperative neurological deficit can be minimized).

Level III

It is recommended that biopsy, partial resection or gross total resection may all be considered in the initial management of malignant glioma depending on the condition of the patient, the size and the location of the malignant glial tumor.

Radiation Therapy

Authors

John Buatti, Timothy C. Ryken, Mark C. Smith, Penny Sneed, John H. Suh, Minesh Mehta, Jeffrey J. Olson

Question

This review focused on the issue of whether radiation therapy is of benefit in the management of patients diagnosed with malignant glioma.

Recommendations

Level 1

Radiation therapy is recommended for the treatment of newly diagnosed malignant glioma in adults. Treatment schemes should include dosage of up to 60 Gy given in 2 Gy daily fractions that includes the enhancing area.

Hypo-fractionated radiation schemes may be used for patients with a poor prognosis and limited survival without compromising response.

Hyper-fractionation and accelerated fractionation have not been shown to be superior to conventional fractionation and are not recommended.

Brachytherapy or stereotactic radiosurgery as a boost to external beam radiotherapy have not been shown to be beneficial and are not recommended in the routine management of newly diagnosed malignant glioma.

Level 2

It is recommended that radiation therapy planning include a 1–2 cm margin around the radiographically defined T1 contrast-enhancing tumor volume or the T2 weighted abnormality on MR imaging.

Cytotoxic Chemotherapeutic Management

Authors

Camilo E. Fadul, Patrick Y. Wen, Lyndon Kim, Jeffrey J. Olson

Question

What is the role of chemotherapy for newly-diagnosed GBM?

Recommendations

Level I

Concurrent and post-irradiation temozolomide is recommended in patients 18–70 years of age with adequate systemic health. This recommendation is supported on evidence from a single class I study.

Level II

BCNU-impregnated biodegradable polymers are recommended in patients for whom craniotomy is indicated. This recommendation based on the evidence from two class II studies.

Level III

The addition of temozolomide to radiation therapy is an option for patients with newly diagnosed glioblastoma (GBM) who are older than 70 years with a Karnofsky performance status (KPS) above 50. For patients 70 years or older with newly diagnosed GBM, temozolomide alone is a well-tolerated alternative to radiation therapy and its benefit might be comparable to that obtained with radiation therapy alone. Radiation therapy followed by one of the nitrosoureas is recommended for those patients who cannot receive temozolomide.

Management of Newly Diagnosed Brain Metastases (Steven N. Kalkanis, MD., task force chairman, published in Journal of Neuro-Oncology in 2010)

Chapter 1 - Role of Whole Brain Radiation Therapy

Authors

Laurie E. Gaspar, Minesh P. Mehta, Roy A. Patchell, Stuart H. Burri, Paula D. Robinson, Rachel E. Morris, Mario Ammirati, David W. Andrews, Anthony L. Asher, Charles S. Cobbs, Douglas Kondziolka, Mark E. Linskey, Jay S. Loeffler, Michael McDermott, Tom Mikkelsen, Jeffrey J. Olson, Nina A. Paleologos, Timothy C. Ryken, Steven N. Kalkanis

Question

Should whole brain radiation therapy (WBRT) be used as the sole therapy in patients with newly-diagnosed, surgically accessible, single brain metastases, compared with WBRT plus surgical resection, and in what clinical settings?

Target population

This recommendation applies to adults with newly diagnosed single brain metastases amenable to surgical resection; however, the recommendation does not apply to relatively radiosensitive tumors histologies (i.e., small cell lung cancer, leukemia, lymphoma, germ cell tumors and multiple myeloma).

Recommendation

Surgical resection plus WBRT versus WBRT alone

Level 1

Class I evidence supports the use of surgical resection plus post-operative WBRT, as compared to WBRT alone, in patients with good performance status (functionally independent and spending less than 50% of time in bed) and limited extracranial disease. There is insufficient evidence to make a recommendation for patients with poor performance scores, advanced systemic disease, or multiple brain metastases.

If WBRT is used, is there an optimal dosing/fractionation schedule?

Target population

This recommendation applies to adults with newly diagnosed brain metastases.

Recommendation

Level 1

Class I evidence suggests that altered dose/fractionation schedules of WBRT do not result in significant differences in median survival, local control or neurocognitive outcomes when compared with “standard” WBRT dose/fractionation. (i.e., 30 Gy in 10 fractions or a biologically effective dose (BED) of 39 Gy10).

If WBRT is used, what impact does tumor histopathology have on treatment

outcomes?

Target population

This recommendation applies to adults with newly diagnosed brain metastases.

Recommendation

Given the extremely limited data available, there is insufficient evidence to support the choice of any particular dose/fractionation regimen based on histopathology. The following question is fully addressed in the surgery guideline paper within this series by Kalkanis et al. Given that the recommendation resulting from the systematic review of the literature on this topic is also highly relevant to the discussion of the role of WBRT in the management of brain metastases, this recommendation has been included below.

Does the addition of WBRT after surgical resection improve outcomes when compared with surgical resection alone?

Target population

This recommendation applies to adults with newly diagnosed single brain metastases amenable to surgical resection.

Recommendation

Surgical resection plus WBRT versus surgical resection alone

Level 1

Surgical resection followed by WBRT represents a superior treatment modality, in terms of improving tumor control at the original site of the metastasis and in the brain overall, when compared to surgical resection alone.

Chapter 2 - Role of Surgical Resection

Authors

Steven N. Kalkanis, Douglas Kondziolka, Laurie E. Gaspar, Stuart H. Burri, Anthony L. Asher, Charles S. Cobbs, Mario Ammirati, Paula D. Robinson, David W. Andrews, Jay S. Loeffler, Michael McDermott , Minesh P. Mehta, Tom Mikkelsen, Jeffrey J. Olson, Nina A. Paleologos, Roy A. Patchell, Timothy C. Ryken, Mark E. Linskey

Question

Should patients with newly-diagnosed metastatic brain tumors undergo open surgical resection versus whole brain radiation therapy (WBRT) and/or other treatment modalities such as radiosurgery, and in what clinical settings?

Target population

These recommendations apply to adults with a newly diagnosed single brain metastasis amenable to surgical resection.

Recommendations

Surgical resection plus WBRT versus surgical resection alone

Level 1

Surgical resection plus WBRT versus SRS ± WBRT

Level 2

Surgical resection plus WBRT, versus stereotactic radiosurgery (SRS) plus WBRT, both represent effective treatment strategies, resulting in relatively equal survival rates. SRS has not been assessed from an evidence-based standpoint for larger lesions (>3 cm) or for those causing significant mass effect (>1 cm midline shift).

Level 3

Underpowered class I evidence along with the preponderance of conflicting class II evidence suggests that SRS alone may provide equivalent functional and survival outcomes compared with resection + WBRT for patients with single brain metastases, so long as ready detection of distant site failure and salvage SRS are possible.

Note The following question is fully addressed in the WBRT guideline paper within this series by Gaspar et al. Given that the recommendation resulting from the systematic review of the literature on this topic is also highly relevant to the discussion of the role of surgical resection in the management of brain metastases, this recommendation has been included below.

Question

Does surgical resection in addition to WBRT improve outcomes when compared with

WBRT alone?

Target population

This recommendation applies to adults with a newly diagnosed single brain metastasis amenable to surgical resection; however, the recommendation does not apply to relatively radiosensitive tumors histologies (i.e., small cell lung cancer, leukemia, lymphoma, germ cell tumors and multiple myeloma).

Recommendation

Surgical resection plus WBRT versus WBRT alone

Level 1

Chapter 3 - Role of Radiosurgery

Authors

Mark E. Linskey, David W. Andrews, Anthony L. Asher, Stuart H. Burri, Douglas Kondziolka, Paula D. Robinson, Mario Ammirati, Charles S. Cobbs, Laurie E. Gaspar, Jay S. Loeffler, Michael McDermott, Minesh P. Mehta,Tom Mikkelsen, Jeffrey J. Olson, Nina A. Paleologos, Roy A. Patchell, Timothy C. Ryken, Steven N. Kalkanis

Question

Should patients with newly-diagnosed metastatic brain tumors undergo stereotactic radiosurgery (SRS) compared with other treatment modalities?

Target population

These recommendations apply to adults with newly diagnosed solid brain metastases amenable to SRS; lesions amenable to SRS are typically defined as measuring less than 3 cm in maximum diameter and producing minimal (less than 1 cm of midline shift) mass effect.

Recommendations

SRS plus WBRT vs. WBRT alone

Level 1

Single-dose SRS along with WBRT leads to significantly longer patient survival compared with WBRT alone for patients with single metastatic brain tumors who have a KPS ≥ 70.

Level 2

Single-dose SRS along with WBRT is superior in terms of local tumor control and maintaining functional status when compared to WBRT alone for patients with 1–4 metastatic brain tumors who have a KPS ≥ 70.

Level 3

Single-dose SRS along with WBRT may lead to significantly longer patient survival than WBRT alone for patients with 2–3 metastatic brain tumors.

Level 4

There is class III evidence demonstrating that single-dose SRS along with WBRT is superior to WBRT alone for improving patient survival for patients with single or multiple brain metastases and a KPS < 70.

SRS plus WBRT vs. SRS alone

Level 2

Single-dose SRS alone may provide an equivalent survival advantage for patients with brain metastases compared with WBRT + single-dose SRS. There is conflicting class I and II evidence regarding the risk of both local and distant recurrence when SRS is used in isolation, and class I evidence demonstrates a lower risk of distant recurrence with WBRT; thus, regular careful surveillance is warranted for patients treated with SRS alone in order to provide early identification of local and distant recurrences so that salvage therapy can be initiated at the soonest possible time.

Surgical Resection plus WBRT vs. SRS ± WBRT

Level 2

Surgical resection plus WBRT, vs. SRS plus WBRT, both represent effective treatment strategies, resulting in relatively equal survival rates. SRS has not been assessed from an evidence-based standpoint for larger lesions (>3 cm) or for those causing significant mass effect (>1 cm midline shift).