Cyberknife radiosurgery on the brainstem metastases of non-small cell lung cancer.

OBJECTIVE: Management of brainstem metastatic tumor is challenging. This study aimed to evaluate overall survival and quality-of-life in patients with non-small cell lung cancer (NSCLC) brainstem metastases who were treated with the Cyberknife stereotactic radiosurgery. METHODS: From August 2007 through August 2016, a total of 32 patients with 34 brainstem metastases of NSCLC were consecutively enrolled and treated with the Cyberknife radiosurgery (CKRS) at The Huashan Hospital. The study was limited to patients with NSCLC, which was confirmed by postoperative pathological examination. Patients were treated by CKRS as an initial treatment or a second treatment after whole-brain radiation therapy (WBRT). Quality of life was assessed by the SF-12 score and neurological examination. RESULTS: Four out of the 32 (12.5%) patients received WBRT before or concurrent with CKRS treatment. The mean survival time after CKRS was 10.0 (95%CI: 6.0-14.0) months. Karnofsky performance score was not the independent predictor of survival after radiosurgery as analyzed by log-rank test (p = 0.392). Age, however, was a significant predictor of improved survival as analyzed by multivariate analysis (p = 0.024). SF-12 physical component scores demonstrated no significant change after treatment. CONCLUSIONS: The CKSR is a non-invasive, safe, and effective modality in the treatment of patients with brainstem metastases of NSCLC. Better therapeutic outcomes of CKSR for brainstem metastasis might be achieved in the patients older than 65 years old.

Extensive craniospinal disseminated metastasis after the resection of intradural extramedullary ependymoma in the craniocervical junction: a case report and literature review.

PURPOSE/AIM: Intradural extramedullary (IDEM) ependymomas are very rare, and IDEM ependymomas with craniospinal disseminated metastasis are exceptionally rare; only 2 preoperative cases have been confirmed, and postoperative cases have not been reported. CASE REPORT: We present a case of a 21-year-old female with an IDEM ependymoma of the craniocervical junction who experienced head and neck pain for more than 1 month. Magnetic resonance imaging (MRI) of the cervical spine revealed a large IDEM cystic lesion located in the medulla oblongata and the upper cervical spinal cord. The patient underwent surgery without complications, and the tumor was completely removed. Histopathological examination revealed a diagnosis of aplastic ependymoma, World Health Organization (WHO) grade III. The patient failed to follow-up with radiotherapy for one month after discharge. Nearly three months after surgery, craniospinal disseminated metastasis was found in the patient; subsequently, chemoradiotherapy was administered to prolong the survival time of the patient. Unfortunately, the patient underwent radiotherapy and chemotherapy for only 7 days; then, the patient gave up treatment and died 5 months later. CONCLUSIONS: To the best of our knowledge, no other cases of craniocervical junction anaplastic ependymomas with craniospinal disseminated metastasis have been reported in the literature. Total resection does not completely prevent recurrence and metastasis, and MRI of the entire neuraxis and timely postoperative craniospinal radiotherapy are necessary for the treatment of this disease.

Too Much on Your "Plate"? Spectrum of Pathologies Involving the Tectal Plate.

The tectal plate comprises the posterior portion of the midbrain, borders the quadrigeminal cistern, and includes the superior and inferior colliculi. Benign and malignant pathologies occurring in this location may lead to aqueductal stenosis, obstructive hydrocephalus, and Parinaud syndrome. Both computed tomography and magnetic resonance imaging can be used to further characterize lesions involving the tectal plate. In this pictorial essay, we review various tectal plate lesions and their imaging features.

Linac-Based Fractionated Stereotactic Radiotherapy with a Micro-Multileaf Collimator for Brainstem Metastasis.

BACKGROUND: To assess the neuroimaging and clinical outcomes in patients with brainstem metastasis (BSM) treated with linac-based fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator. METHODS: Between May 2007 and January 2017, 24 patients (15 male and 9 female) with BSM (25 lesions: midbrain, 10; pons, 13; and medulla oblongata, 2) were consecutively treated with linac-based fSRT. BSM originated from the lung (n = 18, 75.0%), colon (n = 3, 12.5%), and breast (n = 3, 12.5%). The median patient age was 67.0 (range: 42-80) years. Recursive partition analysis classified 2 patients as class I, 17 as class II, and 5 as class III. Overall survival was calculated using the Kaplan-Meier method. RESULTS: Tumor volume ranged from 0.01 to 7.49 cm3 (median: 0.233 cm3), and patients were treated with a dose of 24-40 Gy in 7-13 fractions. The median OS was 9 months after fSRT (95% confidence interval 4.104-13.896). Large tumor volume, presence of brainstem-related symptoms, poor pretreatment Karnofsky performance status, and recursive partition analysis class III were significantly associated with low overall survival. Tumor volume decreased in 18 metastatic lesions, remained stable in 6, and increased in 1. No patient exhibited permanent radiation injury. Grade 2 nausea and vomiting according to the Common Terminology Criteria for Adverse Events 4.0 occurred in 1 patient who received corticosteroids. CONCLUSIONS: Linac-based fSRT with a micro-multileaf collimator delivered in the doses of 24-40 Gy in 7-13 fractions is a safe and effective local therapy for patients with BSM.

The case for radiosurgery for brainstem metastases.

PURPOSE: To challenge the prevalent pessimism regarding the outcome of patients with metastases in the brainstem resulting in the use of whole brain radiation for palliation rather than stereotactic radiosurgery for definitive control and preservation of quality of life. We present our single institution review of the efficacy and safety of treating brainstem metastases aggressively with GKRS. METHODS: Forty-one patients with 45 total lesions treated with GKRS were included. Mean age was 58.7 years, ranging from 22 to 82. Tumor volumes were objectively calculated, treatment effects assessed on imaging and clinical data collected and correlated to the radiosurgical response. RESULTS: Mean survival after diagnosis of BSM was 11.6 months, ranging from 1.4 to 58.8 months. Margin dose ranged from 12 to 20 Gy. At first follow up, 11 (27%) patients had complete resolution of the treated lesion. At the second follow up 15 (37%) and third follow up 19 (46%) patients had a complete response. On average, there was a 64% decrease in tumor size at first follow up after treatment. 25 (61%) patients received WBRT in addition to radiosurgery; 16 (39%) received radiosurgery alone. There was no difference in overall survival between the two groups (p = 0.1324). ARE was seen in one patient who received  16 Gy to the margin of a 2.06 cm3 pontine tumor, but without correlative symptoms. One patient was treated with Bevacizumab® for progressive, but asymptomatic, edema following treatment that was not controlled by corticosteroids. CONCLUSIONS: Location in brainstem should not be a deterrent to the use of radiosurgery for these patients. The addition or exclusion of WBRT should be based on the clinical progression of the patient and within the limits of this study does not seem to impact overall survival. With improved survival as a result of better systemic therapy, these patients can benefit from better preservation of cognitive function by this strategy.

Toxicity of Radiosurgery for Brainstem Metastases.

BACKGROUND: Although stereotactic radiosurgery (SRS) is an effective modality in the treatment of brainstem metastases (BSM), radiation-induced toxicity remains a critical concern. To better understand how severe or life-threatening toxicity is affected by the location of lesions treated in the brainstem, a review of all available studies reporting SRS treatment for BSM was performed. METHODS: Twenty-nine retrospective studies investigating SRS for BSM were reviewed. RESULTS: The rates of grade 3 or greater toxicity, based on the Common Terminology Criteria for Adverse Events, varied from 0 to 9.5% (mean 3.4 ± 2.9%). Overall, the median time to toxicity after SRS was 3 months, with 90% of toxicities occurring before 9 months. A total of 1243 cases had toxicity and location data available. Toxicity rates for lesions located in the medulla were 0.8% (1/131), compared with midbrain and pons, respectively, 2.8% (8/288) and 3.0% (24/811). CONCLUSIONS: Current data suggest that brainstem substructure location does not predict for toxicity and lesion volume within this cohort with median tumor volumes 0.04-2.8 cc does not predict for toxicity.

Investigation of the efficacy and safety of CyberKnife hypofractionated stereotactic radiotherapy for brainstem metastases using a new evaluation criterion: 'symptomatic control'.

The treatment of brainstem metastases remains a challenge as the brainstem itself is considered a neurological organ at risk. We aimed to investigate the efficacy and safety of CyberKnife hypofractionated stereotactic radiotherapy (HFSRT) for brainstem metastases, and to examine the balance between efficacy and safety for the management of neurological symptoms. A total of 26 lesions [pons (n = 18), medulla (n = 4) and midbrain (n = 4)] in 20 patients treated with CyberKnife hypofractionated stereotactic radiotherapy were retrospectively analyzed. The total radiation doses (18-30 Gy) were delivered in 3 or 5 equal fractions. The median follow-up was 6.5 (range, 0.5-38.0) months. The 6- and 12-month local control rates were 100% and 90%, respectively. Symptomatic failures, defined as the worsening and appearance of neurological symptoms due to the brainstem lesion after CyberKnife HFSRT, were observed in 6 patients [local failure (n = 1) and adverse events (n = 5). The symptomatic control and overall survival rates were 90% and 72% (after 6 months), respectively, and 76% and 53% (after 12 months), respectively. Longer symptomatic control was associated with site of lesion origin, and longer overall survival was associated with a graded prognostic assessment score of >2. To our knowledge, this is the second study to investigate the efficacy and safety of CyberKnife HFSRT for brainstem metastases. The local control rate was comparable with that of prior stereotactic radiosurgery studies. We propose a new evaluation criterion-'symptomatic control'-to evaluate the efficacy and safety of brainstem radiotherapy.

Surprising complete response of intramedullary spinal cord metastasis from breast cancer: a case report and literature review.

PURPOSE: Intramedullary spinal cord metastases (ISCM) are considered rare but their incidence is rising. Most ISCM cases are recognized to occur in patients with stage IV lung cancer or breast cancer (BC). METHODS: We report a rare case of cervical BC-ISCM in 60-year-old woman, documented by magnetic resonance imaging and positron emission tomography-computed tomography and treated with volumetric modulated arc therapy with daily image-guided radiation therapy (VMAT/IGRT). RESULTS: An unexpected clinical and radiologic complete response in absence of neurologic side effects was recorded 4 months after VMAT/IGRT. CONCLUSIONS: The present case report shows the feasibility of advanced RT and its optimal response in a case of ISCM from BC. Despite the short follow-up, in comparison with available literature data concerning the management of BC-ISCM, we found an early complete response, in contrast with other reported experiences.

Stereotactic Radiosurgery for Brainstem Metastases: An International Cooperative Study to Define Response and Toxicity.

PURPOSE: To pool data across multiple institutions internationally and report on the cumulative experience of brainstem stereotactic radiosurgery (SRS). METHODS AND MATERIALS: Data on patients with brainstem metastases treated with SRS were collected through the International Gamma Knife Research Foundation. Clinical, radiographic, and dosimetric characteristics were compared for factors prognostic for local control (LC) and overall survival (OS) using univariate and multivariate analyses. RESULTS: Of 547 patients with 596 brainstem metastases treated with SRS, treatment of 7.4% of tumors resulted in severe SRS-induced toxicity (grade ≥3, increased odds with increasing tumor volume, margin dose, and whole-brain irradiation). Local control at 12 months after SRS was 81.8% and was improved with increasing margin dose and maximum dose. Overall survival at 12 months after SRS was 32.7% and impacted by age, gender, number of metastases, tumor histology, and performance score. CONCLUSIONS: Our study provides additional evidence that SRS has become an option for patients with brainstem metastases, with an excellent benefit-to-risk ratio in the hands of experienced clinicians. Prior whole-brain irradiation increases the risk of severe toxicity in brainstem metastasis patients undergoing SRS.

[Neuroendocrine carcinoma of the bladder: A single centre retrospective study]. / Carcinome neuroendocrine de la vessie: étude rétrospective monocentrique.

PURPOSE: Neuroendocrine carcinoma of the bladder is a rare tumour representing 0.5 to 1% of bladder tumours. It is a specific histological entity characterized by rapid metastatic dissemination and poor prognosis. The aim of this study was to describe the epidemiological, clinical, therapeutic modalities and the evolutive aspects of patients receiving a treatment for bladder neuroendocrine carcinoma. PATIENTS AND METHODS: Between January 2004 and January 2014, seven patients received a treatment for a neuroendocrine carcinoma of the bladder, at the department of oncology, Habib-Bourguiba Hospital, in Sfax, Tunisia. RESULTS: The median age was 58 years. All patients were male. Neuroendocrine carcinoma was pure in four cases and associated with urothelial carcinoma in the other three cases. Two patients were diagnosed at a metastatic stage. A cystectomy was performed in two cases. One patient received a chemotherapy and radiotherapy. The other four patients received chemotherapy alone. A single case of complete remission was observed. Median survival was 15 months (5-30 months). One patient is still alive 30 months after diagnosis. CONCLUSION: The management of neuroendocrine carcinoma of the bladder is not standardized and requires a multidisciplinary consultation.

CyberKnife radiosurgery for brainstem metastases: Management and outcomes and a review of the literature.

To our knowledge this paper is the first to use recursive partitioning analysis (RPA) for brainstem metastasis (BSM) patient outcomes, after CyberKnife radiosurgery (CKRS; Accuray, Sunnyvale, CA, USA); nine similar previous publications used mainly Gamma Knife radiosurgery (Elekta AB, Stockholm, Sweden). Retrospective chart reviews from 2006-2013 of 949 CKRS-treated brain metastasis patients showed 54 BSM patients (5.7%): 35 RPA Class II (65%) and 19 Class III (35%). There were 30 women (56%) and 24 men (44%). The median age was 59 years (range 36-80) and median follow-up was 5 months (range 1-52). Twenty-three patients (43%) had lung carcinoma BSM and 12 (22%) had breast cancer BSM. Fifty-four RPA Class II and III BSM patients had a median overall survival (OS) of 5 months, and for each Class 8 and 2 months, respectively. Of 36 RPA Class II and III patients with available symptoms (n=31) and findings (n=33), improvement/stability occurred in the majority for symptoms (86%) and findings (92%). Of 35 cases, 28 (80%) achieved BSM local control (LC); 13/14 with breast histology (93%) and 10/13 with lung histology (77%). All six RPA Class II and III patients with controlled extracranial systemic disease (ESD) experienced LC. Median tumor volume was 0.14 cm(3); of 34 RPA Class II and III cases, 26 LC patients had a 0,13 cm(3) median tumor volume while it was 0.27 cm(3) in the eight local failures. Of 35 cases, single session equivalent dosages less than the median (n=13), at the 17.9 Gy median (n=5) and greater than the median (n=17) had BSM LC in 10 (77%), four (80%) and 14 cases (82%), respectively. Univariate analysis showed Karnofsky Performance Score, RPA Class and ESD-control predicted OS. CKRS is useful for RPA Class II and III BSM patients with effective clinical and local BSM control.

How Does Brainstem Involvement Affect Prognosis in Patients with Limited Brain Metastases? Results of a Matched-Cohort Analysis.

OBJECTIVE: Although brainstem metastases are thought to portend an inferior prognosis compared to non-brainstem brain metastases, there is limited evidence to support this claim, particularly in the modern radiosurgical era. METHODS: We collected the clinical data for 500 patients with brain metastases treated at our institution with stereotactic radiosurgery (SRS). All patients received SRS to at least one brain metastasis, and all brainstem metastases underwent SRS. After propensity score matching, clinical characteristics and overall survival were calculated and compared between groups. RESULTS: Three hundred sixteen patients with brain metastases were analyzed after matching (143 with brainstem involvement and 173 without). Patients with brainstem metastases lived shorter after first SRS than patients without brainstem metastases did (median 4.4 and 6.5 months, respectively; P = 0.01), and they were more likely to have received whole brain irradiation (P = 0.003). Patients with a single metastasis did not survive longer than patients with multiple brain metastases if there was brainstem involvement (P = 0.45). The incidence of new extracranial disease and severe toxicity after SRS did not differ between groups. CONCLUSIONS: The survival of patients with brain metastases is inferior after a metastatic lesion develops within the brainstem, despite favorable local control with brainstem SRS. The brainstem location should be considered a negative prognostic factor for survival after SRS, and it could result from the eloquence of this location. Future research could identify the clinically life-limiting component of brainstem metastases.

Brainstem metastases treated with stereotactic radiosurgery: safety, efficacy, and dose response.

The safety and efficacy of stereotactic radiosurgery (SRS) in the brainstem is questioned by some over concern of violating historical brainstem SRS dose tolerance. Our purpose was to report on the clinical outcomes of patients treated at our institution with radiosurgery for brainstem metastases. Patients with metastatic tumors within or directly abutting the brainstem from 1992 to 2014 were analyzed. Patient and tumor characteristics, SRS parameters, and toxicity were recorded and analyzed for associations with local control and survival. Multivariate statistical analysis was performed using Cox proportional hazards modeling. One-hundred and eighty-nine (189) brainstem metastases from 161 patients were included in our analysis. Whole brain irradiation was administered prior to SRS in 52 % of patients. The median margin dose was 18 Gy prescribed to the 50 % isodose line. Median imaging follow up was 5.4 months and median survival was 5.5 months after SRS. At last follow up, local control was achieved in 87.3 % of brainstem lesions treated. There were 3 recorded events of grade 3-5 toxicity (1.8 %). On multivariate analysis, a margin dose ≥16 Gy was associated with improved local control (p = 0.049) and greater KPS score was associated with improved overall survival following SRS (p = 0.024). Patients with brainstem metastases who have limited intracranial disease and/or who have received whole brain irradiation should be considered for SRS. Margin doses of at least 16 Gy are associated with superior local control, and serious radiation toxicity in SRS for brainstem metastasis appears rare.

Brain Stem and Entire Spinal Leptomeningeal Dissemination of Supratentorial Glioblastoma Multiforme in a Patient during Postoperative Radiochemotherapy: Case Report and Review of the Literatures.

Glioblastoma multiforme (GBM) is the most common primary malignancy of the central nervous system in adults. Macroscopically evident and symptomatic spinal metastases occur rarely. Autopsy series suggest that approximately 25% of patients with intracranial GBM have evidence of spinal subarachnoid seeding, although the exact incidence is not known as postmortem examination of the spine is not routinely performed. Herein, we present a rare case of symptomatic brain stem and entire spinal dissemination of GBM in a 36-year-old patient during postoperative adjuvant radiochemotherapy with temozolomide and cisplatin. Visual deterioration, intractable stomachache, and limb paralysis were the main clinical features. The results of cytological and immunohistochemical tests on the cerebrospinal fluid cells were highly suggestive of spinal leptomeningeal dissemination. After 1 month, the patient's overall condition deteriorated and succumbed to his disease. To the best of our knowledge, this is the first reported case of GBM dissemination presenting in this manner. Because GBM extracranial dissemination is rare, we also reviewed pertinent literature regarding this uncommon entity. Although metastases to spinal cord from GBM are uncommon, it is always important to have in mind when patients with a history of GBM present with symptoms that do not correlate with the primary disease pattern.

Relapse and metastasis of atypical teratoid/rhabdoid tumor in a boy with neurofibromatosis type 1 treated with recombinant human growth hormone.

Even though no increased recurrence rate seems to be reported in patients with brain tumors receiving recombinant human growth hormone (rhGH) replacement, in some patients multiple risk factors could put at higher risk for recurrence. In such cases, the decision to start rhGH therapy should be very cautious. A boy with neurofibromatosis type 1 developed an atypical teratoid/rhabdoid tumor (AT/RT) of right cerebellum, treated with surgery, radiotherapy, and chemotherapy. After 3 years of remission, he started rhGH for growth hormone deficiency, having a negative magnetic resonance imaging (MRI) scan. Ten weeks after starting therapy, the boy became symptomatic and MRI showed relapse of AT/RT in the right cerebellum and a new lesion in the brainstem. The boy died of progressive disease. In this case, the connection between AT/RT recurrence and the beginning of rhGH therapy, with a negative pretreatment MRI, cannot be excluded. Additional caution should be used for rhGH in patients with multiple risk factors.

Management of Hodgkin's lymphoma with midbrain involvement: A case report and review of literature.

Introduction Primary central nervous system (CNS) involvement of Hodgkin's lymphoma is very uncommon. There are only a few previous reports of Hodgkin's lymphoma of nodular lymphocyte predominant histology involving the CNS concurrently with systemic disease. Case presentation A 12-year-old boy with a history of painless left inguinal swelling and acute diplopia. There was an intensely enhancing lesion in the right midbrain on magnetic resonance imaging. The patient was diagnosed with stage IV Hodgkin's lymphoma of nodular lymphocyte predominance type by routine microscopy and immunohistochemistry of left inguinal lymph node biopsy with computed tomography-assisted staging. It was planned to treat him with six cycles of chemotherapy with intrathecal methotrexate, followed by radiotherapy to the CNS lesions. After two cycles of chemotherapy, the patient entered complete remission of all lesions including the CNS lesion documented by the positron emission tomography scan. Conclusion We are describing the course of this rare presentation of Hodgkin's lymphoma of nodular lymphocyte predominant histology involving the CNS and clinical challenge in its diagnosis and management of this case.

Craniospinal irradiation with concurrent temozolomide for primary metastatic pediatric high-grade or diffuse intrinsic pontine gliomas. A first report from the GPOH-HIT-HGG Study Group.

BACKGROUND: High-grade (HGG) and diffuse intrinsic pontine gliomas (DIPG) with primary metastatic spread are extremely rare and have a dismal prognosis. Analogous to simultaneous radiochemotherapy in non-metastatic HGG and DIPG, concurrent craniospinal irradiation (CSI) and metronomic temozolomide (metroTMZ) may represent a reasonable therapeutic approach. However, the antitumor efficacy and toxicity of this treatment still have to be investigated. PATIENTS AND METHODS: Between March 2007 and December 2012, six children with primary metastatic HGG (n = 4) or DIPG (n = 2) received CSI and concurrent metroTMZ based on individual treatment recommendations and, in some cases, within the HIT-HGG 2007 multicenter trial. Outcome and treatment-related toxicities were evaluated. RESULTS: All patients received irradiation to the entire craniospinal axis (35.2 Gy, n = 5; 36 Gy, n = 1:) and 5 received a local boost to macroscopic tumor deposits. Simultaneously, metroTMZ (75 mg/m(2)/day, n = 5; 60 mg/m(2)/day, n = 1) was administered. Additionally, 1 patient received nimotuzumab once per week. Within a median follow-up of 10.0 months (range 6.5-18.7 months), all patients experienced disease progression and 5 patients died. Median progression-free survival was 4.0 ± 0.8 months (range 2.4-10.7 months) and median overall survival was 7.6 ± 3.5 months (range 4.0-17.6 months). Acute myelosuppression most severely limited application of this aggressive treatment strategy. Severe hematotoxicities (≥ grade 3) occurred in all patients and metroTMZ had to be interrupted or discontinued in 4 out of 6 cases. CONCLUSION: Concurrent CSI and metroTMZ might represent a feasible treatment approach for primary metastatic HGG and DIPG. On the basis of our experience, severe but manageable acute hematotoxicity has to be expected. An international effort is warranted to reassess the efficacy and toxicity of this approach within a prospective study.