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Predicting survival in melanoma patients treated with concurrent targeted- or immunotherapy and stereotactic radiotherapy : Melanoma brain metastases prognostic score.

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.

SUBMITTER: Schaule J

PROVIDER: S-EPMC7268472 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Predicting survival in melanoma patients treated with concurrent targeted- or immunotherapy and stereotactic radiotherapy : Melanoma brain metastases prognostic score.

Schaule Jana J Kroeze Stephanie G C SGC Blanck Oliver O Stera Susanne S Kahl Klaus H KH Roeder Falk F Combs Stephanie E SE Kaul David D Claes An A Schymalla Markus M MM Adebahr Sonja S Eckert Franziska F Lohaus Fabian F Abbasi-Senger Nasrin N Henke Guido G Szuecs Marcella M Geier Michael M Sundahl Nora N Buergy Daniel D Dummer Reinhard R Guckenberger Matthias M

Radiation oncology (London, England) 20200601 1

<h4>Background</h4>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).<h4>Methods</h4>This retrospective analysis is ba ...[more]

PMID: 32487100

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Project description:Purpose:Stereotactic radiosurgery (SRS) in combination with immunotherapy (IMT) or targeted therapy is increasingly being used in the setting of melanoma brain metastases (MBMs). The synergistic properties of combination therapy are not well understood. We compared the distant intracranial failure rates of intact MBMs treated with SRS, SRS?+?IMT, and SRS?+?targeted therapy. Methods and materials:Combination therapy was defined as delivery of SRS within 3 months of IMT (anti-CTLA-4 /anti-PD-1 therapy) or targeted therapy (BRAF/MEK inhibitors). The primary endpoint was distant intracranial failure after SRS, which was defined as any new MBM identified on brain magnetic resonance imaging. Outcomes were evaluated using the Kaplan Meier method and Cox proportional hazards. Results:A total of 72 patients with melanoma with 233 MBMs were treated between April 2006 and April 2016. The number of MBMs within each treatment group was as follows: SRS: 121; SRS?+?IMT: 48; and SRS?+?targeted therapy: 64. The median follow-up was 8.9 months. One-year distant intracranial control rates for SRS, SRS?+?IMT, and SRS?+?targeted therapy were 11.5%, 60%, and 10%, respectively (P?<?.001). On multivariate analysis, after adjusting for steroid use and number of MBMs, SRS?+?IMT remained associated with a significant reduction in distant intracranial failure compared with SRS (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.29-0.80; P?=?.003) and compared with SRS?+?targeted therapy (HR, 0.41; 95% CI, 0.25-0.68; P?=?.001).One-year local control for SRS, SRS?+?IMT, and SRS?+?targeted therapy was 66%, 85%, and 72%, respectively (P?=?.044). On multivariate analysis, after adjusting for dose, SRS?+?IMT remained associated with a significant reduction in local failure compared with SRS alone (HR, 0.37; 95% CI, 0.14-0.95; P?=?.04). Conclusions:SRS with immunotherapy is associated with decreased distant and local intracranial failure compared with SRS alone. Prospective studies are warranted to validate this result.

Project description:To report overall survival and local control for patients identified in the RSSearch® Patient Registry with metastatic cancer to the lung treated with SBRT.Seven hundred two patients were identified with lung metastases in the RSSearch® Registry. Of these patients, 577 patients had SBRT dose and fractionation information available. Patients were excluded if they received prior surgery, radiation, or radiofrequency ablation to the SBRT treated area. Between April 2004-July 2015, 447 patients treated with SBRT at 30 academic and community-based centers were evaluable for overall survival (OS). Three hundred four patients with 327 lesions were evaluable for local control (LC). All doses were converted to Monte Carlo equivalents and subsequent BED Gy10 for dose response analysis.Median age was 69 years (range, 18-93 years). Median Karnofsky performance status (KPS) was 90 (range 25/75% 80-100). 49.2% of patients had prior systemic therapy. Median metastasis volume was 10.58 cc (range 25/75% 3.7-25.54 cc). Site of primary tumor included colorectal (25.7%), lung (16.6%), head and neck (11.4%), breast (9.2%), kidney (8.1%), skin (6.5%) and other (22.1%). Median dose was 50 Gy (range 25/75% 48-54) delivered in 3 fractions (range 25/75% 3-5) with a median BED of 100Gy10 (range 25/75% 81-136). Median OS for the entire group was 26 months, with actuarial 1-, 3-, and 5-year OS of 74.1%, 33.3, and 21.8%, respectively. Patients with head and neck and breast cancers had longer median OS of 37 and 32 months respectively, compared to colorectal (30 months) and lung (26 months) which corresponded to 3-year actuarial OS of 51.8 and 47.9% for head and neck and breast respectively, compared to 35.8% for colorectal and 31.2% for lung. The median LC for all patients was 53 months, with actuarial 1-, 3-, and 5-year LC rates of 80.4, 58.9, and 46.3%, respectively. There was no difference in LC by primary histologic type (p?=?0.49). Improved LC was observed for lung metastases that received SBRT doses of BED ?100Gy10 with 3-year LC rate of 77.1% compared to 45% for lung metastases treated with BED?<?100Gy10 (p?=?0.01). Smaller tumor volumes (<11 cc) had improved LC compared to tumor volumes?>?11 cc. (p?=?0.005) Two-year LC rates for tumor volumes?<?11 cc, 11-27 cc and?>?27 cc were 72.9, 64.2 and 45.6%, respectively. This correlated with improved OS with 2-year OS rates of 62.4, 60.9 and 46.2% for tumor volumes?<?11 cc, 11-27 cc and?>?27 cc, respectively (p?=?0.0023). In a subset of patients who received BED ?100Gy10, 2-year LC rates for tumor volumes?<?11 cc, 11-27 cc and?>?27 cc were 82.8, 58.9 and 68.6%, respectively (p?=?0.0244), and 2-year OS rates were 66.0, 58.8 and 28.5%, respectively (p?=?0.0081).Excellent OS and LC is achievable with SBRT utilizing BED ?100Gy10 for lung metastases according to the RSSearch® Registry data. Patients with small lung metastases (volumes?<?11 cc) had better LC and OS when using SBRT doses of BED ?100Gy10. Further studies to evaluate a difference, if any, between various tumor types will require a larger number of patients.

Project description:BackgroundUntil 50% of patients with renal cancer or melanoma, develop brain metastases during the course of their disease. Stereotactic radiotherapy has become a standard of care for patients with a limited number of brain metastases. Given the radioresistant nature of melanoma and renal cancer, optimization of the fractionation of stereotactic radiotherapy is needed. The purpose of this retrospective study was to elucidate if hypofractionated stereotactic radiotherapy (HFSRT) impacts local control of brain metastases from radioresistant tumors such as melanoma and renal cancer, in comparison with radiosurgery (SRS).MethodsBetween 2012 and 2016, 193 metastases, smaller than 3 cm, from patients suffering from radioresistant primaries (melanoma and renal cancer) were treated with HFSRT or SRS. The primary outcome was local progression free survival (LPFS) at 6, 12 and 18 months. Overall survival (OS) and cerebral progression free survival (CPFS) were secondary outcomes, and were evaluated per patient. Objective response rate and radionecrosis incidence were also reported. The statistical analysis included a supplementary propensity score analysis to deal with bias induced by non-randomized data.ResultsAfter a median follow-up of 7.4 months, LPFS rates at 6, 12 and 18 months for the whole population were 83, 74 and 70%, respectively. With respect to fractionation, LPFS rates at 6, 12 and 18 months were 89, 79 and 73% for the SRS group and 80, 72 and 68% for the HFSRT group. The fractionation schedule was not statistically associated with LPFS (HR = 1.39, CI95% [0.65-2.96], p = 0.38). Time from planning MRI to first irradiation session longer than 14 days was associated with a poorer local control rate. Over this time, LPFS at 12 months was reduced from 86 to 70% (p = 0.009). Radionecrosis occurred in 7.1% for HFSRT treated metastases to 9.6% to SRS treated metastases, without any difference according to fractionation (p = 0.55). The median OS was 9.6 months. Six, 12 and 18 months CPFS rates were 54, 24 and 17%, respectively.ConclusionFractionation does not decrease LPFS. Even for small radioresistant brain metastases (< 3 cm), HFSRT, with 3 or 6 fractions, leads to an excellent local control rate of 72% at 1 year with a rate of 7.1% of radionecrosis. HFSRT is a safe and efficient alternative treatment to SRS.

Dataset Information

Predicting survival in melanoma patients treated with concurrent targeted- or immunotherapy and stereotactic radiotherapy : Melanoma brain metastases prognostic score.

Publications

Predicting survival in melanoma patients treated with concurrent targeted- or immunotherapy and stereotactic radiotherapy : Melanoma brain metastases prognostic score.

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