Surgical resection and postoperative radiosurgery versus staged radiosurgery for large brain metastases

Journal of Neuro-Oncology - The purpose of this study was to retrospectively evaluate the new treatment paradigm of staged stereotactic radiosurgery (SRS) for the treatment of large brain...     

Stereotactic radiosurgery of the postoperative resection cavity for brain metastases

PURPOSE: The purpose of this study was to analyze results of adjuvant stereotactic radiosurgery (SRS) targeted at resection cavities of brain metastases without whole-brain irradiation (WBI). METHODS AND MATERIALS: Patients who underwent SRS to the tumor bed, deferring WBI after resection of a brain metastasis, were retrospectively identified. RESULTS: Seventy-two patients with 76 cavities treated from 1998 to 2006 met inclusion criteria. The SRS was delivered to a median marginal dose of 18.6 Gy (range, 15-30 Gy) targeting an average tumor volume of 9.8 cm(3) (range, 0.1-66.8 cm(3)). With a median follow-up of 8.1 months (range, 0.1-80.5 months), 65 patients had follow-up imaging assessable for control analyses. Actuarial local control rates at 6 and 12 months were 88% and 79%, respectively. On univariate analysis, increasing values of conformality indices were the only treatment variables that correlated significantly with improved local control; local control was 100% for the least conformal quartile compared with 63% for the remaining quartiles. Target volume, dose, and number of sessions were not statistically significant. CONCLUSIONS: In this retrospective series, SRS administered to the resection cavity of brain metastases resulted in a 79% local control rate at 12 months. This value compares favorably with historic results with observation alone (54%) and postoperative WBI (80-90%). Given the improved local control seen with less conformal plans, we recommend inclusion of a 2-mm margin around the resection cavity when using this technique.     

Chemosensitized radiosurgery for recurrent brain metastases

Temozolomide is known to penetrate the blood?Cbrain barrier and sensitize brain tumors to radiation and has been used clinically to sensitize fractionated external beam radiotherapy. However, there are limited prospective clinical data available on the safety of temozolomide as a chemosensitizing agent administered with stereotactic radiosurgery. This is a phase I trial of previously irradiated patients with one to four progressive brain metastases and Karnofsky performance scale score ??60?% enrolled in three sequential cohorts: temozolomide 100, 150 or 200?mg/(m² day) administered for 5?days. Stereotactic radiosurgery (SRS) was administered on day 5. The SRS dose was dependent on target diameter: 15?Gy (31?C40?mm), 18?Gy (21?C30?mm) or 21?Gy (<20?mm). The primary endpoint was safety of increasing temozolomide doses. Secondary endpoints included local control and survival. 26 subjects were enrolled and 49 total metastatic lesions were treated. The median number of brain metastases was 1.5, with a median target diameter of 21?mm. The most common grade 1?C2 adverse events irrespective of causality were vomiting (23?%), nausea (23?%), edema (12?%), seizure (8?%), psychosis (4?%) and thrombocytopenia (4?%). The frequency of nausea and vomiting did not appear to be dose-dependent. Grade 3?C4 toxicities were not observed. Median overall survival was 10.2?months. Crude local control was 87.5?%, with a radiological response seen in eight of 24 evaluable patients (33.3?%), and stable disease >6?months in 13 of 24 patients (54.2?%). Temozolomide, at doses up to 200?mg/(m² day)?×?5?days, prior to SRS is well tolerated, with no dose-limiting toxicities in patients with recurrent brain metastases. Local control of target lesions was >80?%.     

脑转移瘤立体定向放射外科治疗

立体定向脑放疗放射外科(SRS)可治疗单发或多发脑转移瘤,与全脑放射治疗(WBRT)相比,能延长生存时间、提高生活质量.用于全身肿瘤控制或稳定、直径≤3.5cm单发脑转移瘤患者,具有与手术配合WBRT相似的疗效.SRS加WBRT与单纯SRS治疗相比,能提高颅内无进展生存期,但未能延长生存时间.脑转移瘤复发后SRS治疗能取得较好疗效.     

Whole-brain radiotherapy and tumor bed radiosurgery following resection of solitary brain metastases

A standard approach to solitary brain metastases is resection followed by whole-brain radiation therapy (WBRT). Despite WBRT, the tumor bed remains a common site of failure. We reviewed outcomes following adjuvant WBRT with tumor bed radiosurgery (SRS). We retrospectively identified patients having undergone neurosurgical resection of a single brain metastasis followed by adjuvant WBRT and tumor bed SRS. SRS dose selection was independent of target volume (10 Gy peripheral dose). Outcomes were calculated actuarially. Patients were censured for local control at the time of last imaging. From 2005 to 2008, 27 patients were treated with WBRT and tumor bed SRS. Median age was 58.7 years, median KPS 80%. The primary malignancy was non-small cell lung cancer in 70%. Median follow-up was 9.7 months. Following the combination of surgery, WBRT and SRS the median overall survival was 17.6 months. Actuarial 2-year local control was 94%. The SRS boost was well tolerated with one patient (4%) requiring reoperation for symptomatic radiation necrosis 16 months post treatment. Radiosurgery can be safely added to WBRT as an adjuvant treatment following resection of a single brain metastasis. In our retrospective series, this combination treatment produced a high rate of local control.     

Stereotactic radiosurgery for the treatment of brain metastases

Background: The objective of this systematic review was to summarise the current evidence concerning radiosurgical treatment (SRS) of newly diagnosed brain metastasis and to compare SRS as a single or additional treatment to treatment alternatives with regard to medical effectiveness and safety.Methods: A structured search of electronic databases was performed to identify relevant publications from 2002 through 2007. Studies targeting patients with brain metastases were included. Standardised quality assessment and data extraction were performed.Results: Of 1496 publications, 16 studies were included. The mean survival in most studies was less than 12 months. There was evidence that SRS plus WBRT was associated with improved local tumour control and neurological functioning compared to either treatment alone. Only in patients with single metastasis, this resulted in improved survival. There was inconclusive evidence when comparing SRS to WBRT, Neurosurgery (NS) or Hypofractionated Radiotherapy (HCSRT). The Quality of life (Qol) was not investigated.Conclusion: SRS plus WBRT was associated with improved local tumour control and neurological functioning compared to either treatment alone. Only in certain patients, this resulted in improved survival. Methodologically rigorous studies are therefore warranted to investigate further treatment options, and in view of the poor prognosis, to investigate Qol and neurological functioning.     

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.     

Stereotactic radiosurgery for brain metastases from hepatocellular carcinoma

The purpose of this study is to investigate the possible role of stereotactic radiosurgery (SRS) in the management of patients with brain metastases from hepatocellular carcinoma (HCC). Thirty-two consecutive patients with 80 brain metastases from HCC were treated with SRS. Twenty-eight (87.5 %) patients were male, and the mean age of the patients was 54 ± 12 years (range 22–73). Twenty-seven (84.4 %) patients were classified as RTOG RPA Class 2. The mean tumor volume was 6.14 ± 11.3 cm³ (range 0.01–67.3). The mean marginal dose prescribed was 20.1 ± 3.6 Gy (range 10.0–25.0). The median overall survival time after SRS was 11.3 ± 5.8 weeks (95 % CI 0–22.7). A greater total volume of brain metastases (>14 cm³) was the only independent prognostic factor (HR = 2.419; 95 % CI 1.040–5.624; p = 0.040). The actuarial control rate of brain metastases was 51.3 % at 4 months after SRS. The prescribed marginal dose (>18 Gy) was significantly related with the actuarial tumor control (HR = 0.254; 95 % CI 0.089–0.725; p = 0.010). The prognosis of patients with brain metastases from HCC is dismal even with the modern technology of radiosurgery. The marginal dose prescribed should be reevaluated to improve upon the current poor local control rates.     

Pulmonary resection in patients with nonsmall-cell lung cancer treated with gamma-knife radiosurgery for synchronous brain metastases

BACKGROUND: The aim of the current study was to determine whether a pulmonary resection and gamma-knife radiosurgery (GKRS) protocol is superior to GKRS alone in selected patients with stage IV nonsmall-cell lung cancer (NSCLC). METHODS: The authors performed a retrospective case-control study of 232 consecutive patients with newly diagnosed NSCLC from January 1998 to December 2005 and screened them to identify a study cohort in which all patients had thoracic stage I or II, Karnofsky performance status >or= 70, no extracranial metastases, and 1-3 synchronous brain metastases of less than 3 cm, and were treated with GKRS (n=31). The study cohort was divided into 2 groups, those with and without concomitant pulmonary resection. RESULTS: Sixteen patients with pulmonary resection were assigned to the treatment group and 15 without pulmonary resection were assigned to the control group. Median follow-up was 27.3 months (range, 4.4 months to 90.9 months). Mean survivals for the treatment group and the control group were 64.9 and 18.1 months, respectively (P< .001). There was a statistically significant association between pulmonary resection and better survival (OR=78.408). One-year and 5-year local brain tumor control rates were 97.1% and 93.5%, respectively. CONCLUSIONS: The pulmonary resection and GKRS protocol could prolong survival in patients with thoracic stage I or II NSCLC, no extracranial metastases, and a limited number of small synchronous brain metastases.     

A comparison of surgical resection and stereotactic radiosurgery in the treatment of solitary brain metastases

PURPOSE: To determine whether neurosurgery (NS) or stereotactic radiosurgery (RS) provided better local tumor control and enhanced patient survival. METHODS AND MATERIALS: Retrospective review of all solitary brain metastases (SBM) patients newly diagnosed at Mayo Clinic Rochester between 1991 and 1999. Eligible patients satisfied tumor size and SBM site criteria to qualify for both NS and RS. RESULTS: There were no significant differences between 74 NS and 23 RS patients in terms of baseline characteristics (age, gender, systemic disease type, systemic disease status, signs/symptoms at SBM presentation) or percent of patients who received whole brain radiotherapy. Median follow-up for alive patients was 20 months (range 0-106 months). There was no significant difference in patient survival (p = 0.15); the 1-year survival rate was 56% for the RS patients and 62% for the NS patients. Multivariate Cox regression analysis found that a significant prognostic factor for survival was a performance score of 0 or 1. There was a significant (p = 0.020) difference in local tumor control between NS and RS for solitary brain metastasis; none of the RS group had local recurrence compared to 19 (58%) of the NS group. CONCLUSION: The need for a Phase III study comparing these two techniques appears to be supported by the data from this study.     

Stereotactic radiosurgery for brain metastases: results and prognostic factors

This study was conducted to determine prognostic factors for tumor response and patient survival after stereotactic radiosurgery (SRS) for brain metastasis. Eighty-four patients with brain metastasis underwent SRS at a single institution. After fixation of the head with a stereotactic frame, computed tomography treatment planning was performed. The metastatic lesion was treated with multiple arcs to a median dose of 19 Gy. Forty-seven patients (56%) had a solitary brain lesion. Fifty-nine patients (70%) had evidence of extracranial disease at the time of SRS. The median survival duration from SRS was 7 months. Sixty-three percent of the patients had an objective radiographic response to SRS, which in turn was associated with superior central nervous system control. Age, collimator size, number of arcs, tumor location, and histology did not influence objective response rates. Patients who had a solitary lesion or who received treatment within 2 weeks after diagnosis were more likely to have an objective response than were those who did not (P < 0.05). Progressive brain disease accounted for 37% of the deaths. Nineteen patients (23%) had an in-field relapse. Four severe complications were attributed to SRS. This study confirms the role of SRS as an acceptable treatment option for patients with solitary or limited brain metastases. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 157-162 (2000).     

Stereotactic radiosurgery for multiple brain metastases from breast carcinoma

BACKGROUND: The current study analyzed the feasibility and outcome of stereotactic radiosurgery (SRS) for treatment of brain metastases from breast carcinoma. METHODS: During an 8-year period, 151 patients with a combined total of 620 brain metastases from breast carcinoma underwent 197 outpatient SRS procedures. Sixty-three percent of all patients had multiple brain metastases. The median tumor volume was 2.2 cm(3) (range, 0.1-20.9 cm(3)). The mean prescribed tumor dose was 19 +/- 4 grays. Local/distant tumor recurrences were treated with additional radiosurgical therapy for patients with stable systemic disease. All patients were categorized according to the Radiation Therapy Oncology Group classification. Survival time and freedom from local tumor recurrence were analyzed using the Kaplan-Meier method. Prognostic factors were identified using the Cox proportional hazards model. RESULTS: The overall median survival duration was 10 months after SRS. Ninety-four percent of patients did not experience local brain tumor recurrence after radiosurgery. In addition, 70.2% of patients did not have disease recurrence in the brain. Most patients died of systemically progressing malignancy. A Karnofsky performance score > 70 and recursive partitioning analysis Class I were related to prolonged survival in the univariate and multivariate analyses. Age, whole-brain radiotherapy, surgery, number of metastases, chemotherapy, and latency period from diagnosis of the primary tumor to the development of brain metastases did not reach prognostic relevance in the multivariate model. Patients with RPA I, II, and III survived 34.9, 9.1, and 7.9 months, respectively. There was no treatment related permanent morbidity and mortality. The transient morbidity rate was 17%. Sixteen patients exhibited symptomatic transient complications related to treatment. CONCLUSIONS: The results of the current study indicate that SRS is a feasible treatment concept for selected patients with multiple brain metastases from breast carcinoma.     

Long-term survivors after gamma knife radiosurgery for brain metastases

BACKGROUND: Stereotactic radiosurgery, with or without whole-brain radiation therapy, has become a valued management choice for patients with brain metastases, although their median survival remains limited. In patients who receive successful extracranial cancer care, patients who have controlled intracranial disease are living longer. The authors evaluated all brain metastasis in patients who lived for > or = 4 years after radiosurgery to determine clinical and treatment patterns potentially responsible for their outcome. METHODS: Six hundred seventy-seven patients with brain metastases underwent 781 radiosurgery procedures between 1988 and 2000. Data from the entire series were reviewed; and, if patients had > or = 4 years of survival, then they were evaluated for information on brain and extracranial treatment, symptoms, imaging responses, need for further care, and management morbidity. These long-term survivors were compared with a cohort who lived for < 3 months after radiosurgery (n = 100 patients). RESULTS: Forty-four patients (6.5%) survived for > 4 years after radiosurgery (mean, 69 mos with 16 patients still alive). The mean age at radiosurgery was 53 years (maximum age, 72 yrs), and the median Karnofsky performance score (KPS) was 90. The lung (n = 15 patients), breast (n = 9 patients), kidney (n = 7 patients), and skin (melanoma; n = 6 patients) were the most frequent primary sites. Two or more organ sites outside the brain were involved in 18 patients (41%), the primary tumor plus lymph nodes were involved in 10 patients (23%), only the primary tumor was involved in 9 patients (20%), and only brain disease was involved in 7 patients (16%), indicating that extended survival was possible even in patients with multiorgan disease. Serial imaging of 133 tumors showed that 99 tumors were smaller (74%), 22 tumors were unchanged (17%), and 12 tumors were larger (9%). Four patients had a permanent neurologic deficit after brain tumor management, and six patients underwent a resection after radiosurgery. Compared with the patients who had limited survival (< 3 mos), long-term survivors had a higher initial KPS (P = 0.01), fewer brain metastases (P = 0.04), and less extracranial disease (P < 0.00005). CONCLUSIONS: Although the expected survival of patients with brain metastases may be limited, selected patients with effective intracranial and extracranial care for malignant disease can have prolonged, good-quality survival. The extent of extracranial disease at the time of radiosurgery was predictive of outcome, but this does not necessarily mean that patients cannot live for years if treatment is effective.     

Stereotactic radiosurgery for brain metastases from malignant melanoma and the impact of hemorrhagic metastases

Central nervous system (CNS) tumors are a leading cause of death in pediatric oncology. New drugs are desperately needed to improve survival. We evaluated the outcome of children and adolescents with CNS tumors participating in phase I trials within the Innovative Therapies for Children with Cancer (ITCC) consortium. Patients with solid tumors aged?<?18 years at enrollment in their first dose-finding trial between 2000 and 2014 at eight ITCC centers were included retrospectively. Survival was evaluated using univariate/multivariate analyses. Overall, 114 patients were included (109 evaluable for efficacy). Median age was 10.2 years (range 1.0–17.9). Main diagnoses included: medulloblastoma/primitive neuroectodermal tumors (32.5%) and high-grade gliomas (23.7%). Complete/partial responses (CR/PR) were reported in 7.3% patients and stable disease (SD) in 23.9%. Performance status of 90–100%, school/work attendance, normal ALT/AST and CR/PR/SD correlated with better overall survival (OS) in the univariate analysis. No variables assessable at screening/enrollment were associated with OS in the multivariate analysis. Five patients (4.5%) were discontinued from study due to toxicity. No toxic deaths occurred. Median OS was 11.9 months with CR/PR, 14.5 months with SD and 3.7 months with progressive disease (p?<?0.001). The enrollment of children and adolescents with CNS tumors in phase I trials is feasible, safe and offers potential benefit for the patients. Sustained disease stabilization has a promising role as a marker of anti-tumor activity in children with CNS tumors participating in phase I trials.     

Indications and approach to surgical resection of lung metastases

Pulmonary metastasectomy is a curative option for selected patients with cancer spread to the lungs. Complete surgical removal of pulmonary metastases can improve survival and is recommended under certain criteria. Specific issues that require consideration in a multidisciplinary setting when planning pulmonary metastasectomy include: adherence to established indications for resection, the surgical strategy including the use of minimally invasive techniques, pulmonary parenchyma preservation, and the role of lymphadenectomy. J. Surg. Oncol. 2010;102:187–195. © 2010 Wiley‐Liss, Inc.     

Immune checkpoint inhibitors and radiosurgery for newly diagnosed melanoma brain metastases

As survival rates have improved owing to advances in management strategies for pediatric brain tumors, long-term complications such as endocrine dysfunction, have emerged as a major issue. This study investigated the long-term endocrine effects of childhood-onset brain tumors in a large number of patients. This study included 151 patients with brain tumors diagnosed between January 1995 and December 2016. The following data were retrospectively reviewed: tumor location, tumor histology, endocrine abnormalities, hypothalamic involvement on brain imaging, treatment modalities, and trends in body mass index. The mean age at diagnosis of patients with sellar/suprasellar (SE/SUP-SE) tumors and supra/infratentorial (ST/IT) tumors was 9.9?±?4.5 and 6.5?±?4.2 years, respectively. In patient with prepubertal age at diagnosis, height standard deviation score was lower in patients with SE/SUP-SE tumors at diagnosis (P?=?0.031), which was lower in patients with ST/IT tumors at the final visit (P?<?0.001). The prevalence of combined pituitary hormone deficiencies was higher among patients with SE/SUP-SE tumors than in those with ST/IT tumors (81.7 vs. 36.1%, P?<?0.001). Among 98 non-obese patients with SE/SUP-SE tumors, 36.7% developed obesity. The prevalence of combined pituitary hormone deficiencies and obesity was higher in patients with SE/SUP-SE tumors than in those with tumors in other locations; growth impairment was more severe in patients with ST/IT tumors.