scholarly journals Predicting survival in melanoma patients treated with concurrent targeted- or immunotherapy and stereotactic radiotherapy

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Jana Schaule ◽  
Stephanie G. C. Kroeze ◽  
Oliver Blanck ◽  
Susanne Stera ◽  
Klaus H. Kahl ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Systemic Therapy ◽  
Stereotactic Radiotherapy ◽  
Local Therapy ◽  
Whole Brain Radiotherapy ◽  
Brain Radiotherapy ◽  
Kaplan Meier ◽  
Mixed Treatment ◽  
Melanoma Patients

Abstract Background Melanoma patients frequently develop brain metastases. The most widely used score to predict survival is the molGPA based on a mixed treatment of stereotactic radiotherapy (SRT) and whole brain radiotherapy (WBRT). In addition, systemic therapy was not considered. We therefore aimed to evaluate the performance of the molGPA score in patients homogeneously treated with SRT and concurrent targeted therapy or immunotherapy (TT/IT). Methods This retrospective analysis is based on an international multicenter database (TOaSTT) of melanoma patients treated with TT/IT and concurrent (≤30 days) SRT for brain metastases between May 2011 and May 2018. Overall survival (OS) was studied using Kaplan-Meier survival curves and log-rank testing. Uni- and multivariate analysis was performed to analyze prognostic factors for OS. Results One hundred ten patients were analyzed. 61, 31 and 8% were treated with IT, TT and with a simultaneous combination, respectively. A median of two brain metastases were treated per patient. After a median follow-up of 8 months, median OS was 8.4 months (0–40 months). The molGPA score was not associated with OS. Instead, cumulative brain metastases volume, timing of metastases (syn- vs. metachronous) and systemic therapy with concurrent IT vs. TT influenced OS significantly. Based on these parameters, the VTS score (volume-timing-systemic therapy) was established that stratified patients into three groups with a median OS of 5.1, 18.9 and 34.5 months, respectively (p = 0.001 and 0.03). Conclusion The molGPA score was not useful for this cohort of melanoma patients undergoing local therapy for brain metastases taking into account systemic TT/IT. For these patients, we propose a prognostic VTS score, which needs to be validated prospectively.

scholarly journals Hypofractionated stereotactic radiotherapy with or without whole-brain radiotherapy for patients with newly diagnosed brain metastases from non–small cell lung cancer

2012 ◽  
Vol 117 (Special_Suppl) ◽  
pp. 49-56 ◽  
Author(s):  
Liang-Hua Ma ◽  
Guang Li ◽  
Hong-Wei Zhang ◽  
Zhi-Yu Wang ◽  
Jun Dang ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiotherapy ◽  
Whole Brain Radiotherapy ◽  
Tumor Control ◽  
Newly Diagnosed ◽  
Small Cell Lung ◽  
Hypofractionated Stereotactic Radiotherapy ◽  
Brain Radiotherapy ◽  
Kaplan Meier ◽  
Multiple Metastases

Object This study was undertaken to analyze outcomes in patients with newly diagnosed brain metastases from non–small cell lung cancer (NSCLC) who were treated with hypofractionated stereotactic radiotherapy (HSRT) with or without whole-brain radiotherapy (WBRT). Methods One hundred seventy-one patients comprised the study population. Fifty-four patients received HSRT alone, and 117 patients received both HSRT and WBRT. The median survival time (MST) was determined using the Kaplan-Meier method. Recursive Partitioning Analysis (RPA) and Graded Prognostic Assessment (GPA) were also used to evaluate the results. Univariate and multivariate analyses were performed to determine significant prognostic factors for overall survival. Tumor control, radiation toxicity, and cause of death in the HSRT and HSRT+WBRT groups were evaluated. Results The MST for all patients was 13 months. According to the Kaplan-Meier method, the probability of survival at 1, 2, and 3 years was 51.2%, 21.7%, and 10.1%. The MSTs for RPA Classes I, II, and III were 19, 12, and 5 months, respectively; and the MSTs for GPA Scores 4, 3, 2, and 1 were 24, 14, 12, and 6 months, respectively. The MSTs in the HSRT+WBRT and HSRT groups were 13 and 9 months (p = 0.044), respectively, for all patients, 13 and 8 months (p = 0.031), respectively, for patients with multiple brain metastases, and 16 and 15 months (p = 0.261), respectively, for patients with a single brain metastasis. The multivariate analysis showed that HSRT+WBRT was a significant factor only for patients with multiple brain metastases (p = 0.010). The Kaplan-Meier–estimated tumor control rates at 3, 6, 9, and 12 months were 92.2%, 82.7%, 79.5%, and 68.3% in the HSRT+WBRT group and 73.5%, 58.4%, 51.0%, and 43.3% in the HSRT group, respectively, in all 165 patients (p = 0.001). The estimated tumor control rates at 3, 6, 9, and 12 months were 94.3%, 81.9%, 79.6%, and 76.7%, respectively, in the HSRT+WBRT group and 77.8%, 61.4%, 52.6%, and 48.2%, respectively, in the HSRT group in the 80 patients harboring a single metastasis (p = 0.009). The estimated tumor control rates at 3, 6, 9, and 12 months were 90.5%, 83.5%, 79.5%, and 60.9%, respectively, in the HSRT+WBRT group and 68.2%, 54.5%, 48.5%, and 36.4%, respectively, in the HSRT group in the 85 patients with multiple metastases (p = 0.010). The toxicity incidences of Grade 3 or worse were 6.0% (7 of 117 patients) in the HSRT+WBRT group and 1.9% (1 of 54 patients) in the HSRT group (p = 0.438). The differences in neurological death rates between the HSRT+WBRT group and the HSRT group were not statistically significant (34.4% vs 44.7%, p = 0.125, in all patients; 30.0% vs 52.0%, p = 0.114, in patients with a single metastasis; and 38.0% vs 36.4%, p = 0.397, in patients with multiple metastases). Conclusions The overall survival results in the present study were similar to those in other studies. Hypofractionated stereotactic radiotherapy provides an alternative method to traditional stereotactic radiosurgery. We suggest that WBRT should be combined with HSRT in patients with single or multiple newly diagnosed brain metastases from NSCLC.

scholarly journals Hippocampal avoidance whole-brain radiotherapy without memantine in preserving neurocognitive function for brain metastases: a phase II blinded randomized trial

2020 ◽  
Author(s):  
Wen-Chi Yang ◽  
Ya-Fang Chen ◽  
Chi-Cheng Yang ◽  
Pei-Fang Wu ◽  
Hsing-Min Chan ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Phase Ii ◽  
Whole Brain Radiotherapy ◽  
Neurocognitive Function ◽  
Mean Difference ◽  
Whole Brain ◽  
Delayed Recall ◽  
Brain Radiotherapy ◽  
Hippocampal Avoidance

Abstract Background Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) shows potential for neurocognitive preservation. This study aimed to evaluate whether HA-WBRT or conformal WBRT (C-WBRT) is better for preserving neurocognitive function. Methods This single-blinded randomized phase II trial enrolled patients with brain metastases and randomly assigned them to receive HA-WBRT or C-WBRT. Primary endpoint is decline of the Hopkins Verbal Learning Test–Revised (HVLT-R) delayed recall at 4 months after treatment. Neurocognitive function tests were analyzed with a mixed effect model. Brain progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Results From March 2015 to December 2018, seventy patients were randomized to yield a total cohort of 65 evaluable patients (33 in the HA-WBRT arm and 32 in the C-WBRT arm) with a median follow-up of 12.4 months. No differences in baseline neurocognitive function existed between the 2 arms. The mean change of HVLT-R delayed recall at 4 months was −8.8% in the HA-WBRT arm and +3.8% in the C-WBRT arm (P = 0.31). At 6 months, patients receiving HA-WBRT showed favorable perpetuation of HVLT-R total recall (mean difference = 2.60, P = 0.079) and significantly better preservation of the HVLT-R recognition-discrimination index (mean difference = 1.78, P = 0.019) and memory score (mean difference = 4.38, P = 0.020) compared with patients undergoing C-WBRT. There were no differences in Trail Making Test Part A or Part B or the Controlled Oral Word Association test between the 2 arms at any time point. There were no differences in brain PFS or OS between arms as well. Conclusion Patients receiving HA-WBRT without memantine showed better preservation in memory at 6-month follow-up, but not in verbal fluency or executive function.

Multidisciplinary Approach to Brain Metastasis from Melanoma: The Emerging Role of Systemic Therapies

2013 ◽  
pp. 393-398 ◽  
Author(s):  
Georgina V. Long ◽  
Kim A. Margolin
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Local Therapy ◽  
Whole Brain Radiotherapy ◽  
Brain Radiotherapy ◽  
First Line Therapy ◽  
Melanoma Brain Metastases

Melanoma brain metastases are common, difficult to treat, and carry a poor prognosis. Until recently, systemic therapy was ineffective. Local therapy (including surgery, stereotactic radiotherapy, and whole brain radiotherapy) was considered the only option for a chance of disease control in the brain, and was highly dependent on the patient's performance status and age, number and size of brain metastases, and the presence of extracranial metastases. Since 2010, three drugs have demonstrated activity in progressing or “active” brain metastases including the anti-CTLA4 antibody ipilimumab (phase II study of 72 patients), and the BRAF inhibitors dabrafenib (phase II study of 172 patients, both previously treated and untreated brain metastases) and vemurafenib (a pilot study of 24 patients with heavily pretreated brain metastases). The challenge and unanswered question for clinicians is how to sequence all the available therapies, both local and systemic, to optimize the patient's quality of life and survival. This is an area of intense clinical research. The treatment of patients with melanoma brain metastases should be discussed by a multidisciplinary team of melanoma experts including a neurosurgeon, medical oncologist, and radiation oncologist. Important clinical features that help determine appropriate first line therapy include single compared with solitary brain metastasis, resectablity, BRAF mutation status of melanoma, rate of progression/performance status, and the presence of extracranial disease.

scholarly journals RADI-32. INTRACRANIAL CONTROL AND RADIONECROSIS IN MELANOMA PATIENTS WITH BRAIN METASTASES TREATED WITH STEREOTACTIC RADIOSURGERY

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i28-i28
Author(s):  
Michael Tjong ◽  
Fabio Moraes ◽  
David Shultz
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Local Control ◽  
Brain Mri ◽  
Lesion Size ◽  
Kaplan Meier ◽  
Prescription Dose ◽  
Melanoma Patients ◽  
The Brain

Abstract PURPOSE/OBJECTIVE(S): Melanoma commonly metastasizes to the brain and is radioresistant. Stereotactic radiosurgery (SRS) confers durable local control of brain metastases (BM) while maintaining neurocognitive function. These advantages are increasingly important as survival among these patients improves secondary to advances in systemic therapies. This study investigated the local control (LC), intracranial PFS (iPFS), freedom from radionecrosis (FFRN), and overall survival (OS) among melanoma patients receiving SRS for BM. MATERIALS/METHODS: We retrospectively reviewed clinical outcomes of melanoma patients with brain metastases treated with SRS between October 2008 and January 2017 in a large academic centre. Post-SRS, patients were followed in a multidisciplinary clinic with clinical examination and brain MRI every 3 months. Survival outcomes were estimated using the Kaplan-Meier method. RESULTS: In total, 97 patients with 283 brain metastases (including 12 surgical cavities) treated with SRS were identified. Median age was 60.5 (24.4–90.7). Median follow-up was 9.6 (2.2–74.7) months after first SRS. Median prescription dose was 21 (10–24) Gy delivered in a single fraction. Thirty (30.9%) patients had WBRT post-SRS, 36 (37.1%) patients had BRAF-positive disease. Per lesion (N=283), 1-year LC and FFRN were 84.4%, and 90.1%, respectively; medians were not achieved for either LC or FFRN. Radionecrosis (RN) occurred in 20 (7.1%) lesions. Per patient (N=97), median OS and iPFS were 16.0 and 5.3 months, respectively; 1-year OS and iPFS rates were 62.0%, and 30.1%, respectively. CONCLUSION: SRS resulted in excellent rates of LC, with a low risk of RN. However, most patients developed intracranial progression within 1 year. Further analyses to establish correlates (lesion size, SRS dose, and molecular status) to LC, FFRN, OS, and iPFS will be performed prior to the final presentation.

Phase II trial of sunitinib as adjuvant therapy after stereotactic radiosurgery (SRS) in patients with 1-3 newly diagnosed brain metastases.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2018-2018
Author(s):  
David M. Peereboom ◽  
Samuel T. Chao ◽  
John H. Suh ◽  
Ding Wang ◽  
Tom Mikkelsen ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Brain Metastases ◽  
Systemic Disease ◽  
Neuropsychological Testing ◽  
Local Therapy ◽  
Whole Brain Radiotherapy ◽  
Growth Factor Signaling ◽  
Newly Diagnosed ◽  
Brain Radiotherapy ◽  
Primary Disease

2018 Background: For patients with 1-3 brain metastases, standard therapy after SRS is adjuvant whole brain radiotherapy (WBRT). SRS without WBRT carries a higher rate of brain relapse. Due to concerns about neurologic sequelae of WBRT, however, many patients and physicians opt to defer WBRT until the time of central nervous system (CNS) progression. This trial used sunitinib as an alternative to WBRT for post-SRS adjuvant therapy. Sunitinib inhibits vascular endothelial growth factor signaling, and we hypothesized that it would prevent growth of microscopic brain metastases presumed to be present. The objective was to use adjuvant sunitinib after SRS to prevent the emergence of new or progressive disease in the brain or at the site of SRS and to preserve neurocognitive function. Methods: Eligible patients had 1-3 newly diagnosed brain metastases, RTOG RPA class 1-2, and started sunitinib < 1 month after SRS and baseline neuropsychological testing (NPT). Patients with controlled systemic disease were allowed to continue chemotherapy for their primary disease according to a list of published regimens (therapy + sunitinib) included in the protocol. Patients received sunitinib 37.5 or 50 mg/d days 1-28 every 42 days until CNS progression. NPT and MRIs were obtained every 2 cycles. The primary endpoint was the rate of CNS progression at 6 months (PFS6) after SRS. Results: Fourteen patients enrolled. The median age was 59 (range 46-80). Main histologies: lung 36%, breast 21%, melanoma 14%. Toxicities: Grade 4: neutropenia [ANC] (1 pt); Grade 3: fatigue (5), ANC (2), rash (1). Dose reduction due to toxicity: 1 pt (to 37.5 mg/d). The CNS PFS6 and PFS12 were 50% + 13% and 43% + 13%, respectively. The median PFS was 6.6 months (95% C.I. 1.5-19). NPT results will be reported at the meeting. Conclusions: Sunitinib after SRS for 1-3 brain metastases was well tolerated with a PFS6 of 50%. The use of novel agents to prevent progressive brain metastasis after SRS requires the incorporation of chemotherapy regimens to control the patient’s primary disease. Future trials should continue to explore the paradigm of secondary chemoprevention of brain metastases after definitive local therapy (surgery or SRS).

Evaluation of Stereotactic Radiotherapy of the Resection Cavity After Surgery of Brain Metastases Compared to Postoperative Whole-Brain Radiotherapy (ESTRON)—A Single-Center Prospective Randomized Trial

Neurosurgery ◽  
2018 ◽  
Vol 83 (3) ◽  
pp. 566-573 ◽  
Author(s):  
Rami A El Shafie ◽  
Angela Paul ◽  
Denise Bernhardt ◽  
Henrik Hauswald ◽  
Thomas Welzel ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiotherapy ◽  
Randomized Study ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
Locoregional Control ◽  
Single Center ◽  
Whole Brain ◽  
Resection Cavity ◽  
Brain Radiotherapy

Abstract BACKGROUND Neurosurgical resection is recommended for symptomatic brain metastases, in oligometastatic patients or for histology acquisition. Without adjuvant radiotherapy, roughly two-thirds of the patients relapse at the resection site within 24 mo, while the risk of new metastases in the untreated brain is around 50%. Adjuvant whole-brain radiotherapy (WBRT) can reduce the risk of both scenarios of recurrence significantly, although the associated neurocognitive toxicity is substantial, while stereotactic radiotherapy (SRT) improves local control at comparably low toxicity. OBJECTIVE To compare locoregional control and treatment-associated toxicity for postoperative SRT and WBRT after the resection of 1 brain metastasis in a single-center prospective randomized study. METHODS Fifty patients will be randomized to receive either hypofractionated SRT of the resection cavity and single- or multisession SRT of all unresected brain metastases (up to 10 lesions) or WBRT. Patients will be followed-up regularly and the primary endpoint of neurological progression-free survival will be assessed by magnetic resonance imaging (MRI). Quality of life and neurocognition will be assessed in 3-mo intervals using standardized tests and EORTC questionnaires. EXPECTED OUTCOMES We expect to show that postoperative SRT of the resection cavity and further unresected brain metastases is a valid means of improving locoregional control over observation at less neurocognitive toxicity than caused by WBRT. DISCUSSION The present study is the first to compare locoregional control as well as neurocognitive toxicity for postoperative SRT and WBRT in patients with up to 10 metastases, while utilizing a highly sensitive and standardized MRI protocol for treatment planning and follow-up.

Re-Irradiation of Brain Metastases and Metastatic Spinal Cord Compression: Clinical Practice Suggestions

2005 ◽  
Vol 91 (4) ◽  
pp. 325-330 ◽  
Author(s):  
Ernesto Maranzano ◽  
Fabio Trippa ◽  
Diamante Pacchiarini ◽  
Luigia Chirico ◽  
Maria Luisa Basagni ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Stereotactic Radiotherapy ◽  
Whole Brain Radiotherapy ◽  
Cord Compression ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Radiation Induced ◽  
The Brain

The recent improvements of therapeutic approaches in oncology have allowed a certain number of patients with advanced disease to survive much longer than in the past. So, the number of cases with brain metastases and metastatic spinal cord compression has increased, as has the possibility of developing a recurrence in areas of the central nervous system already treated with radiotherapy. Clinicians are reluctant to perform re-irradiation of the brain, because of the risk of severe side effects. The tolerance dose for the brain to a single course of radiotherapy is 50–60 Gy in 2 Gy daily fractions. New metastases appear in 22–73% of the cases after whole brain radiotherapy, but the percentage of re-irradiated patients is 3–10%. An accurate selection must be made before giving an indication to re-irradiation. Patients with Karnofsky performance status >70, age <65 years, controlled primary and no extracranial metastases are those with the best prognosis. The absence of extracranial disease was the most significant factor in conditioning survival, and maximum tumor diameter was the only variable associated with an increased risk of unacceptable acute and/or chronic neurotoxicity. Re-treatment of brain metastases can be done with whole brain radiotherapy, stereotactic radiosurgery or fractionated stereotactic radiotherapy. Most patients had no relevant radiation-induced toxicity after a second course of whole brain radiotherapy or stereotactic radiosurgery. There are few data on fractionated stereotactic radiotherapy in the re-irradiation of brain metastases. In general, the incidence of an “in-field” recurrence of spinal metastasis varies from 2.5–11% of cases and can occur 2–40 months after the first radiotherapy cycle. Radiation-induced myelopathy can occur months or years (6 months-7 years) after radiotherapy, and the pathogenesis remains obscure. Higher radiotherapy doses, larger doses per fraction, and previous exposure to radiation could be associated with a higher probability of developing radiation-induced myelopathy. Experimental data indicate that also the total dose of the first and second radiotherapy, interval to re-treatment, length of the irradiated spinal cord, and age of the treated animals influence the risk of radiation-induced myelopathy. An α/β ratio of 1.9–3 Gy could be generally the reference value for fractionated radiotherapy. However, when fraction sizes are up to 5 Gy, the linear-quadratic equation become a less valid model. The early diagnosis of relapse is crucial in conditioning response to re-treatment.

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