Initial clinical experience with frameless radiosurgery for patients with intracranial metastases

PURPOSE: To review the initial clinical experience with frameless stereotactic radiosurgery (SRS) for treating intracranial metastatic disease. METHODS AND MATERIALS: Sixty-four patients received frameless SRS for intracranial metastatic disease. Minimum follow-up was 6 months with none lost to follow-up. Patients had a median of 2 metastases and a maximum of 4. The median number of isocenters was 2 with median arcs of 10 and median dose of 17.5 Gy. Thirteen patients were treated for progressive/recurrent disease after surgical resection or whole brain radiotherapy (WBRT). Fifty-one patients were treated with frameless SRS as an an adjunct to initial treatment. Of the total treated, 17 were treated with SRS alone, 20 were treated with WBRT plus SRS, 16 were treated with surgical resection plus SRS, and the remaining 11 were treated with surgical resection plus WBRT plus SRS. RESULTS: With a median actuarial follow-up period of 8.2 months, ultimate local control was 88%. The median time to progression was 8.1 months. The median overall survival was 8.7 months. Of the 17 patients treated with SRS alone, 86% had ultimate local control with mean overall survival of 7.1 months. Of the 13 patients who received surgical resection plus SRS without WBRT as primary treatment, there was 85% ultimate local control with an overall survival of 10.3 months. Three patients treated with initial surgery alone had recurrence treated with SRS 2-3 months after resection. All these patients obtained local control and median survival was >10 months. Of the 13 patients who received WBRT followed by SRS as boost treatment, 92% had local control and mean overall survival was 7.3 months. Of 7 patients who received SRS after recurrence after WBRT, 100% had local control with median survival of 8.2 months. For 8 patients who received surgery followed by WBRT and SRS, local control was 50%; however, ultimate intracranial control was achieved in 7 of 8 patients with repeat SRS and surgical resection. The overall survival in this group of patients was 14.7 months. No patient had a serious (Grade 3 or higher) complication requiring intervention. CONCLUSIONS: Frameless optically guided radiosurgery is less invasive, can be performed as a standard radiotherapy-based simulation procedure, and maintains submillimetric accuracy. Our initial results with frameless SRS for metastatic disease suggest survival times and local control (88%) eqiuvalent to frame-based methodologies. Practical noninvasive delivery makes treatment and potential retreatment to avoid WBRT more feasible.     

Cyberknife radiosurgery for breast cancer spine metastases: a matched-pair analysis

BACKGROUND: There are few options for breast cancer patients with spinal metastases recurrent within a previous radiation treatment field. CyberKnife radiosurgery has been used in our institution to treat such patients. To evaluate their outcomes, as there are no comparable radiation treatment options, the outcomes were compared between 18 patients with spinal metastases from breast cancer treated with CyberKnife stereotactic radiosurgery, 17 of which had prior radiotherapy to the involved spinal region and were progressing, and 18 matched patients who received conventional external beam radiotherapy (CRT) up-front for spinal metastases. METHODS: Radiosurgery was delivered in 3 to 5 fractions to doses ranging from 2100 to 2800 cGy. Women were matched to patients in a CRT group with respect to time from original diagnosis to diagnosis of metastases, estrogen receptor / progesterone receptor (ER/PR) status, presence or absence of visceral metastases, prior radiotherapy, and prior chemotherapy. Survival and complications were compared between treatment groups. Surviving patients were followed out to 24 months. RESULTS: The CyberKnife and CRT groups were comparable along all matching dimensions and in performance status before treatment. Outcomes of treatment were similar for patients in both groups; ambulation, performance status, and pain worsened similarly across groups posttreatment. Survival and the number of complications appeared to favor the CyberKnife group, but the differences did not reach statistical significance. CONCLUSIONS: The statistical comparability of the CyberKnife and CRT groups reflects the small sample size and stringent requirements for significance of the matched-pair analysis. Nevertheless, comparability in these difficult cases shows that salvage CyberKnife treatment is as efficacious as initial CRT without added toxicity.     

Stereotactic radiosurgery for the treatment of bulky spine metastases

Journal of Neuro-Oncology - Stereotactic radiosurgery (SRS) has shown durable local control for the treatment of metastatic diseasespinal metastases. Multilevel disease or epidural or paraspinal...     

Gamma Knife radiosurgery for brainstem metastases: the UCSF experience

Purpose: To assess clinical and imaging outcomes in patients treated with Gamma Knife stereotactic radiosurgery (SRS) for brainstem metastases. Materials and methods: We reviewed all patients with brain metastases treated with SRS at the University of California, San Francisco from 1991–2005 to identify patients who had SRS to a brainstem metastasis. Survival time and freedom from progression (FFP) were calculated from date of SRS using the Kaplan–Meier method. Prognostic factors were evaluated using the log-rank test and Cox proportional hazards model. Results: From 1991 through 2005, 42 consecutive patients with brainstem metastases had SRS to 44 lesions (seven midbrain, 31 pontine, and six medullary) in 42 sessions. Primary diagnoses included 14 cases of lung cancer (one small-cell), 10 melanoma, 12 breast cancer, five renal cell, and one unknown. The median age was 55 years (range, 25–79). The median survival time was 9 months after SRS. Longer survival time was associated with single metastasis, non-melanoma histology, and extracranial disease control. The median target volume was 0.26 ml (0.015–2.8 ml) and the median prescribed dose was 16.0 Gy (10.0–19.8 Gy). Brainstem lesion FFP was 90% at 6 months and 77% at 1 year. Four patients had brainstem complications following treatment. Poor brainstem outcome was associated with melanoma and renal cell histology as well as brainstem lesion volume ≥1 ml. Conclusions: In this series, SRS using a median dose of 16 Gy provided excellent local control with relatively low morbidity in patients with brainstem metastases less than 1 ml or non-melanoma, non-renal cell histology.     

Initial clinical experience with a frameless and maskless stereotactic radiosurgery treatment

PurposeTo evaluate the initial clinical experience with a frameless and maskless technique for stereotactic radiosurgery using minimal patient immobilization and real-time patient motion monitoring during treatment. We focus on the evaluation of the patient treatment process.Methods and MaterialsThe study considered the first 23 patients treated with this technique. Head positioning was achieved with a patient-specific head mold made out of expandable foam that conforms to the patient's head. The face of the patient is left open for maximal comfort and so that motion of a region of interest consisting of the forehead, nose, eyes, and temporal bones can be monitored during treatment using a video surface imaging system (VisionRT Inc, London, UK). Initial setup of the patient was performed with the surface imaging system using the surface of the patient obtained from the treatment planning computed tomographic (CT) scan. The initial setup was confirmed and finalized with cone-beam CT (CBCT) prior to treatment. The shifts for final setup based on the CBCT and the duration of all the steps in the treatment process were recorded. Patients were monitored during treatment with surface imaging, and a beam hold-off was initiated when the patient's motion exceeded a prespecified tolerance.ResultsThe average total setup time including surface imaging and CBCT was 26 minutes, while the portion corresponding to surface imaging was 14 minutes. The average treatment time from when the patient was placed on the treatment table until the last treatment beam was 40 minutes. Eight (35%) patients needed repositioning during the treatment. The average shifts identified from CBCT after initial setup with surface imaging were 1.85 mm in the anterior-posterior direction, and less than 1.0 mm in the lateral and superior-inferior directions. The longest treatment times (including beam hold-offs) happened for patients who fell asleep on the treatment table and were moving involuntarily.ConclusionsThe frameless and maskless treatment using minimal immobilization and surface imaging has proven to be reasonably fast for routine clinical use. We observed that patient compliance is important. An additional degree of semi-rigid immobilization would be helpful for patients who fall asleep and involuntarily move during the procedure.     

Gamma knife radiosurgery for management of cerebral metastases from esophageal carcinoma

Esophageal carcinoma rarely results in intracranial metastases but when it does, the patient prognosis is grim. Because of its rarity outcomes after stereotactic radiosurgery (SRS) are not known. We sought to evaluate the outcomes of SRS in the management of esophageal cancer that has spread to the brain. This single institution retrospective analysis reviewed our experience with esophageal metastasis from 1987 to 2013. Thirty patients (36 SRS procedures) with a median age of 59 (37–86 years) underwent Gamma knife^® SRS. The esophageal origin was adenocarcinoma in 26 patients (87 %), squamous cell carcinoma in 3 patients (10 %), and mixed neuroendocrine carcinoma in 1 patient (3 %). Fifteen patients were treated for a single metastasis and 15 patients were treated for multiple metastases for a total of 87 tumors. The median tumor volume was 5.7 cm³ (0.5–44 cm³) with a median marginal dose of 17 Gy (12–20 Gy). The median survival time from the diagnosis of brain metastasis was 8 months and the median survival from SRS was 4.2 months. This corresponded to a 6-month survival of 45 % and a 12-month survival of 19 % after SRS. A higher KPS at the time of procedure was associated with an increase in survival (p = 0.023). The local tumor control rate in this group was 92 %. Four patients had repeat SRS for new metastatic deposits. One patient developed a new neurological deficit after SRS. SRS proved an effective means of providing local control for esophageal metastases to the brain. Concomitant systemic disease progression at the time of brain metastasis resulted in poor long-term survival.     

The role of stereotactic radiosurgery in the management of patients with newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline

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). 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.     

Integration of immuno-oncology with stereotactic radiosurgery in the management of brain metastases

Journal of Neuro-Oncology - Brain metastases traditionally carried a poor prognosis with treatment being a combination of surgery, whole-brain radiation therapy, and glucocorticoids; however, this...     

Resection versus radiosurgery for patients with brain metastases

Brain metastases occur in 20-40% of adult cancer patients and the incidence is apparently increasing. Despite advances in treatment, the prognosis of these patients is poor, with a median survival of approximately 4 months. Whole brain radiation therapy is the standard of care for most patients with brain metastases. Randomized trials have demonstrated that focal treatments, such as resection and radiosurgery, yield significant improvement in the survival of patients with a single metastasis. The utility of these strategies, specifically in terms of increased survival, is unclear in patients with more than one metastasis. In addition to focal treatments, future directions in the treatment of brain metastases include the development of intraoperative imaging capabilities, improved methods of identifying patients who are likely to benefit from treatment, systemic agents, such as chemotherapy and radiosensitizers, and the incorporation of targeted and antiangiogenic therapies.     

Fractionated stereotactic radiosurgery for patients with brain metastases

Stereotactic radiosurgery (SRS) delivered in 2–5 fractions (multi-fraction SRS) has been employed in patients with brain metastases as an alternative to single-fraction SRS with the aim to reduce late radiation-induced toxicity while maintaining high local control rate. In the present study we have evaluated the efficacy and toxicity of multi-fraction SRS in patients with 1–3 brain metastases. Between March 2006 and October 2012, 135 patients (63 men and 72 women) with 171 brain metastases have been treated with multi-fraction SRS (3 × 9 Gy or 3 × 12 Gy). At a median follow-up of 11.4 months, 16 lesions recurred locally. The 1- and 2-year local control rates were 88 and 72 %, respectively. The 1- and 2-year survival rates were 57 and 25 %, and respective distant failure rates were 52 and 73 %. Seventy-eight percent of patients succumbed to their extracranial disease and 22 % died of progressive intracranial disease. Multivariate analysis showed that melanoma histology was predictive of local failure (p = 0.02; HR 6.1, 95 % CI 1.5–24). Specifically, the 1-year local control rates were 68 % for melanoma, 92 % for breast carcinoma, and 88 % for NSCLC, respectively. Stable extracranial disease (p = 0.004) and Karnofsky performance status (p = 0.01) were predictive of longer survival. Radiologic changes suggestive of radionecrosis occurred in 12 (7 %) out of 171 lesions, with an actuarial risk of 9 % at 1 year and 17 % at 2 years, respectively. In conclusion, multi-fraction SRS appears to be an effective and safe treatment modality for brain metastases. It may represent an alternative to single-dose SRS for patients with large lesions or lesions located near critical structures.     

Initial clinical experience with frameless stereotactic radiosurgery: analysis of accuracy and feasibility.

PURPOSE: To report on preliminary clinical experience with a novel image-guided frameless stereotactic radiosurgery system. METHODS AND MATERIALS: Fifteen patients ranging in age from 14 to 81 received radiosurgery using a commercially available frameless stereotactic radiosurgery system. Pathologic diagnoses included metastases (12), recurrent primary intracranial sarcoma (1), recurrent central nervous system (CNS) lymphoma (1), and medulloblastoma with supratentorial seeding (1). Treatment accuracy was assessed from image localization of the stereotactic reference array and reproducibility of biteplate reseating. We chose 0.3 mm vector translation error and 0.3 degree rotation about each axis as the maximum tolerated misalignment before treating each arc. RESULTS: The biteplates were found on average to reseat with a reproducibility of 0.24 mm. The mean registration error from CT localization was found to be 0.5 mm, which predicts that the average error at isocenter was 0.82 mm. No patient treatment was delivered beyond the maximum tolerated misalignment. The radiosurgery treatment was delivered in approximately 25 min per patient. CONCLUSION: Our initial clinical experience with stereotactic radiotherapy using the infrared camera guidance system was promising, demonstrating clinical feasibility and accuracy comparable to many frame-based systems.     

Indications for resection and radiosurgery for brain metastases

PURPOSE OF REVIEW: This review is focused on indications for resection, stereotactic radiosurgery, and fractionated radiotherapy for patients with single or multiple brain metastases. Our purpose is to summarize the indications and effect of these management approaches. RECENT FINDINGS: Brain metastases are a frequent challenge in patients with extracranial solid cancers. More than 40% of patients with cancer will develop metastases to the brain. While some patients present with large lesions and symptoms related to mass effect, many are diagnosed when asymptomatic tumors are found on screening studies. The main options for patients with brain metastases are whole brain radiation therapy, surgical resection, and stereotactic radiosurgery. Much information regarding outcomes, survival, management morbidity, and quality of life is available. Randomized, class III clinical trials demonstrate that multimodal therapy is important for both life quality and extended survival. A better understanding of the current therapeutic options should result in improvements in patient care. SUMMARY: This is a review of the literature from May 2004 to June 2005 with special attention on publications related to effect on quality of life with different procedures and therapies.     

Cerebral metastases pathology after radiosurgery: a multicenter study

BACKGROUND: To the authors' knowledge, comprehensive human pathologic investigations that explore fundamental radiosurgical effects on metastatic brain tumors are sparse in the literature. The objective of this study was to analyze histopathologic findings in a set of clinically recurrent cerebral metastases after patients underwent stereotactic radiosurgery (SRS). METHODS: In a series of 7500 patients who underwent radiosurgery, 2020 patients (27%) harbored cerebral metastases. Eighteen of 2020 patients (0.9%) underwent subsequent craniotomy for tumor removal anywhere from 1 month to 59 months after they received high-dose irradiation. Histologic and immunohistochemical investigations were performed on the surgically resected tissue specimens. These specimens were within the radiosurgical treatment volume of the metastatic tumor. RESULTS: Light microscopy revealed 3 basic categories of histologic responses: acute-type, subacute-type, and chronic-type tissue reactions. A moderate-to-intense inflammatory cell reaction was seen in the tissue responses of well controlled neoplasms (i.e., in patients who had neoplasms that required craniotomy for recurrent disease > 5 months after SRS), whereas the inflammatory reaction was missing or sparse in poorly controlled neoplasms (patients who required craniotomy for recurrent disease < 5 months after SRS). This reaction was seen within the irradiated tumor volume and not in the peritumoral area nor in areas remote from the radiosurgical treatment volume. Immunohistochemical characterization demonstrated the presence of prominent CD68-positive macrophage and CD3-positive T-lymphocyte populations. A progressively severe vasculopathy also was observed with increasing time after radiosurgery. CONCLUSIONS: Although causality has not been established, a brisk inflammatory response and more severe vasculopathy were observed in lesions in which recurrences were more delayed.     

Treatment of brainstem metastases with gamma-knife radiosurgery

The aim was to investigate the efficacy and safety of gamma-knife stereotactic radiosurgery (SRS) for treating brainstem metastases. The cases of 44 patients who underwent SRS as treatment for 46 brainstem metastases were retrospectively evaluated. The median age was 57 years (range 42–82 years) and the median Karnofsky performance score (KPS) was 80 (range 60–90). The primary tumor was lung carcinoma in 28 cases, breast carcinoma in 7 cases, colon carcinoma in 3 cases, renal cell carcinoma in 3 cases, malignant melanoma in 1 case, and unknown origin in 2 cases. Of the 46 metastases, 30 were in the pons, 14 were in the mesencephalon, and 2 were in the medulla oblongata. The median volume of the 46 metastases was 0.6 cc (range 0.34–7.3 cc). The median marginal dose of radiation was 16 Gy (range 10–20 Gy). Twenty-three patients (52 %) received whole brain radiotherapy prior to SRS, and 6 (14 %) received this therapy after SRS. In the remaining 15 cases (34 %), SRS was applied as the only treatment. Recursive partitioning analysis, graded prognostic assessment, and basic score for brain metastases were used to predict survival time. Local control was achieved for all but two of the 46 metastases (96 %). The overall survival time after SRS was 8 months. Female gender, KPS >70, mesencephalon tumor location, and response to treatment were associated with longer survival. Basic score for brain metastases class I and recursive partitioning analysis classification were associated with better prognosis. Peri-tumoral changes were detected radiologically at 2 (4 %) of the metastatic lesion sites but neither of these patients exhibited symptoms. Gamma-knife radiosurgery is effective for treating brainstem metastases without a higher risk for radiation necrosis.