Faculty Bibliography

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 > or = 70.Level 1 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 > or =70.Level 2 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 3 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 [corrected].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). 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. SRS alone vs. WBRT alone Level 3 While both single-dose SRS and WBRT are effective for treating patients with brain metastases, single-dose SRS alone appears to be superior to WBRT alone for patients with up to three metastatic brain tumors in terms of patient survival advantage.

PURPOSE: To analyze the outcomes of gamma knife stereotactic radiosurgery (SRS) for residual or recurrent craniopharyngiomas and evaluate the factors that optimized the tumor control rates. METHODS AND MATERIALS: A total of 46 patients with craniopharyngiomas underwent 51 SRS procedures at University of Pittsburgh between 1988 and 2007. The median tumor volume was 1.0 cm(3) (range, 0.07-8.0). The median prescription dose delivered to the tumor margin was 13.0 Gy (range, 9-20). The median maximal dose was 26.0 Gy (range, 20-50). The mean follow-up time was 62.2 months (range, 12-232). RESULTS: The overall survival rate after SRS was 97.1% at 5 years. The 3- and 5-year progression-free survival rates (solid tumor control) were both 91.6%. The overall local control rate (for both solid tumor and cyst control) was 91%, 81%, and 68% at 1, 3, and 5 years, respectively. No patients with normal pituitary function developed hypopopituitarism after SRS. Two patients developed homonymous hemianopsia owing to tumor progression after SRS. Among the factors examined, complete radiosurgical coverage was a significant favorable prognostic factor. CONCLUSION: SRS is a safe and effective minimally invasive option for the management of residual or recurrent craniopharyngiomas. Complete radiosurgical coverage of the tumor was associated with better tumor control.

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 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. Surgical resection plus WBRT versus SRS + or - 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: 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 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. 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 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 extra-cranial disease. There is insufficient evidence to make a recommendation for patients with poor performance scores, advanced systemic disease, or multiple brain metastases.

TARGET POPULATION: This recommendation applies to adults with newly diagnosed brain metastases; however, the recommendation below does not apply to the exquisitely chemosensitive tumors, such as germinomas metastatic to the brain. RECOMMENDATION: Should patients with brain metastases receive chemotherapy in addition to whole brain radiotherapy (WBRT)? Level 1 Routine use of chemotherapy following WBRT for brain metastases has not been shown to increase survival and is not recommended. Four class I studies examined the role of carboplatin, chloroethylnitrosoureas, tegafur and temozolomide, and all resulted in no survival benefit. Two caveats are provided in order to allow the treating physician to individualize decision-making: First, the majority of the data are limited to non small cell lung (NSCLC) and breast cancer; therefore, in other tumor histologies, the possibility of clinical benefit cannot be absolutely ruled out. Second, the addition of chemotherapy to WBRT improved response rates in some, but not all trials; response rate was not the primary endpoint in most of these trials and end-point assessment was non-centralized, non-blinded, and post-hoc. Enrollment in chemotherapy-related clinical trials is encouraged.

OBJECTIVE: Patients with intracranial aneurysms, both ruptured and unruptured, are frequently eligible for both open surgery ("clipping") and endovascular repair ("coiling"). Although results of randomized trials have informed this decision, the actual choice of clipping or coiling for individual patients remains complex. At the 2007 Congress of Neurological Surgeons (CNS) Annual Meeting, a novel active learning process called Integrated Medical Learning (IML) was applied to education about this critical treatment choice. METHODS: CNS members received an electronically distributed premeeting survey and educational materials about the clipping versus coiling decision and related topics. At the Annual Meeting, participants used handheld devices to choose clipping or coiling for treatment of individual aneurysms, both before and after expert opinion presentations. After the meeting, members who had answered premeeting surveys received a follow-up questionnaire. RESULTS: In the premeeting poll, respondents with self-described specialties of "vascular," Cerebrovascular Section members, surgeons with active cerebrovascular practices, and surgeons in practice for less than 20 years had higher levels of baseline knowledge of cerebrovascular literature (P < .03). Surgeons' clinical volumes of clipping and coiling strongly influenced their vote for clipping or coiling for a hypothetical patient (P < .01). At the meeting, in 6 of 8 cases of ruptured aneurysms the audience was split 75%:25% or closer to "clinical equipoise" (50:50 split). Surgeons with vascular specialty, academic surgeons, and residents were more likely to recommend clipping for individual cases (P < .05). After experts' presentations, in 6 of 8 cases the audience opinion changed significantly. Vascular specialists and younger surgeons were less likely to change their opinion (P < .03). The 2 cases with no shift in opinion were the most-clippable and most-coilable cases. Postmeeting surveys showed evidence of retained knowledge from the meeting, and respondents thought IML had been helpful. CONCLUSIONS: Using IML, we were able to study baseline knowledge and practice patterns for an important cerebrovascular treatment decision. Evidence suggested that expert presentations were effective in changing audience opinion, at least in cases where preexisting opinion was close to clinical equipoise.