Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Radiation Oncology
Published in: Radiation Oncology 1/2020

Open Access 01-12-2020 | Metastasis | Research

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

Melanoma brain metastases prognostic score

Authors: Jana Schaule, Stephanie G. C. Kroeze, Oliver Blanck, Susanne Stera, Klaus H. Kahl, Falk Roeder, Stephanie E. Combs, David Kaul, An Claes, Markus M. Schymalla, Sonja Adebahr, Franziska Eckert, Fabian Lohaus, Nasrin Abbasi-Senger, Guido Henke, Marcella Szuecs, Michael Geier, Nora Sundahl, Daniel Buergy, Reinhard Dummer, Matthias Guckenberger

Published in: Radiation Oncology | Issue 1/2020

Login to get access

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.
Literature
1.
Patel JK, Didolkar MS, Pickren JW, Moore RH. Metastatic pattern of malignant melanoma. A study of 216 autopsy cases. Am J Surg. 1978;135:807–10.CrossRef
2.
Sampson JH, Carter JH, Friedman AH, Seigler HF. Demographics, prognosis, and therapy in 702 patients with brain metastases from malignant melanoma. J Neurosurg. 1998;88:11–20.CrossRef
3.
Gaudy-Marqueste C, Dussouil AS, Carron R, et al. Survival of melanoma patients treated with targeted therapy and immunotherapy after systematic upfront control of brain metastases by radiosurgery. Eur J Cancer. 2017;84:44–54.CrossRef
4.
Goyal S, Silk AW, Tian S, Mehnert J, Danish S, Ranjan S, et al. Clinical Management of Multiple Melanoma Brain Metastases: a systematic review. JAMA Oncol. 2015;1:668–76.CrossRef
5.
Long GV, Atkinson V, Lo S, et al. Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol. 2018;19:672–81.CrossRef
6.
Tawbi HA, Forsyth PA, Algazi A, et al. Combined Nivolumab and Ipilimumab in melanoma metastatic to the brain. N Engl J Med. 2018;379:722–30.CrossRef
7.
Davies MA, Saiag P, Robert C, et al. Dabrafenib plus trametinib in patients with BRAFV600-mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial. Lancet Oncol. 2017;18:863–73.CrossRef
8.
Dummer R, Goldinger SM, Turtschi CP, Eggmann NB, Michielin O, Mitchell L, et al. Vemurafenib in patients with BRAFV600 mutation-positive melanoma with symptomatic brain metastases: final results of an open-label pilot study. Eur J Cancer. 2014;50:611–21.CrossRef
9.
Kocher M, Soffietti R, Abacioglu U, et al. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J Clin Oncol. 2011;29:134–41.CrossRef
10.
Yamamoto M, Serizawa T, Shuto T, et al. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol. 2014;15:387–95.CrossRef
11.
Shultz DB, Modlin LA, Jayachandran P, et al. Repeat courses of stereotactic radiosurgery (SRS), deferring whole-brain irradiation, for new brain metastases after initial SRS. Int J Radiat Oncol Biol Phys. 2015;92:993–9.CrossRef
12.
Rauschenberg R, Bruns J, Brütting J, et al. Impact of radiation, systemic therapy and treatment sequencing on survival of patients with melanoma brain metastases. Eur J Cancer. 2019;110:11–20.CrossRef
13.
Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, Wasserman T, et al. Recursive partitioning analysis (RPA) of prognostic factors in three radiation therapy oncology group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys. 1997;37:745–51.CrossRef
14.
Golden DW, Lamborn KR, McDermott MW, Kunwar S, Wara WM, Nakamura JL, et al. Prognostic factors and grading systems for overall survival in patients treated with radiosurgery for brain metastases: variation by primary site. J Neurosurg. 2008;109(Suppl):77–86.CrossRef
15.
Sperduto PW, Berkey B, Gaspar LE, Mehta M, Curran W. A new prognostic index and comparison to three other indices for patients with brain metastases: an analysis of 1,960 patients in the RTOG database. Int J Radiat Oncol Biol Phys. 2008;70:510–4.CrossRef
16.
Sperduto PW, Chao ST, Sneed PK, et al. Diagnosis-specific prognostic factors, indexes, and treatment outcomes for patients with newly diagnosed brain metastases: a multi-institutional analysis of 4,259 patients. Int J Radiat Oncol Biol Phys. 2010;77:655–61.CrossRef
17.
Sperduto PW, Jiang W, Brown PD, et al. Estimating survival in melanoma patients with brain metastases: an update of the graded prognostic assessment for melanoma using molecular markers ( melanoma-molGPA ). Radiat Oncol Biol. 2017;99:812–6.
18.
Nieder C, Hintz M, Bilger A, Oehlke O, Grosu A. Validation of the graded prognostic assessment for melanoma using molecular markers ( melanoma-molGPA ). J Clin Med Res. 2018;10:178–81.CrossRef
19.
Rice SR, Bentzen SM, Hanna A, et al. Prognostic models for patients with brain metastases after stereotactic radiosurgery with or without whole brain radiotherapy: a validation study. J Neuro-Oncol. 2018;140:341–9.CrossRef
20.
Badakhshi H, Engeling F, Budach V, Ghadjar P, Zschaeck S, Kaul D. Are prognostic indices for brain metastases of melanoma still valid in the stereotactic era? Radiat Oncol. 2018;13:1–6.CrossRef
21.
Kano H, Morales-Restrepo A, Iyer A, Weiner GM, Mousavi SH, Kirkwood JM, et al. Comparison of prognostic indices in patients who undergo melanoma brain metastasis radiosurgery. J Neurosurg. 2018;128:14–22.CrossRef
22.
Choong ES, Lo S, Drummond M, Fogarty GB, Menzies AM, Guminski A, et al. Survival of patients with melanoma brain metastasis treated with stereotactic radiosurgery and active systemic drug therapies. Eur J Cancer. 2017;75:169–78.CrossRef
23.
Minniti G, Anzellini D, Reverberi C, Cappellini GCA, Marchetti L, Bianciardi F, et al. Stereotactic radiosurgery combined with nivolumab or Ipilimumab for patients with melanoma brain metastases: evaluation of brain control and toxicity. J Immunother Cancer. 2019;7:102.CrossRef
24.
25.
Williams NL, Wuthrick EJ, Kim H, et al. Phase 1 study of Ipilimumab combined with whole brain radiation therapy or radiosurgery for melanoma patients with brain metastases. Int J Radiat Oncol. 2017;99:22–30.CrossRef
26.
Twyman-Saint Victor C, Rech AJ, Maity A, et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature. 2015;520:373–7.CrossRef
27.
28.
Patel KR, Lawson DH, Kudchadkar RR, Carthon BC, Oliver DE, Okwan-Duodu D, et al. Two heads better than one? Ipilimumab immunotherapy and radiation therapy for melanoma brain metastases. Neuro-Oncology. 2015;17:1312–21.CrossRef
29.
Mangana J, Cheng PF, Kaufmann C, et al. Multicenter , real-life experience with checkpoint inhibitors and targeted therapy agents in advanced melanoma patients in Switzerland. Melanoma Res. 2017;27:358–68.CrossRef
30.
Knisely JPS, Yu JB, Flanigan J, Sznol M, Kluger HM, Chiang VLS. Radiosurgery for melanoma brain metastases in the ipilimumab era and the possibility of longer survival. J Neurosurg. 2012;117:227–33.CrossRef
31.
32.
Pires da Silva I, Wang KYX, Wilmott JS, et al. Distinct molecular profiles and immunotherapy treatment outcomes of V600E and V600K BRAF -mutant melanoma. Clin Cancer Res. 2019;25:1272–9.CrossRef
33.
Stera S, Balermpas P, Blanck O, et al. Stereotactic radiosurgery combined with immune checkpoint inhibitors or kinase inhibitors for patients with multiple brain metastases of malignant melanoma. Melanoma Res. 2019;29:187–95.CrossRef
34.
35.
Weltman E, Salvajoli JV, Brandt RA, de Morais HR, Prisco FE, Cruz JC, et al. Radiosurgery for brain metastases: a score index for predicting prognosis. Int J Radiat Oncol Biol Phys. 2000;46:1155–61.CrossRef
36.
Likhacheva A, Pinnix CC, Parikh N, et al. Validation of recursive partitioning analysis and diagnosis-specific graded prognostic assessment in patients treated initially with radiosurgery alone. J Neurosurg. 2012;117(Suppl):38–44.CrossRef
37.
Dummer R, Hauschild A, Lindenblatt N, Pentheroudakis G, Keilholz U. Cutaneous melanoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26:v126–32.CrossRef
Metadata
Title
Predicting survival in melanoma patients treated with concurrent targeted- or immunotherapy and stereotactic radiotherapy
Melanoma brain metastases prognostic score
Authors
Jana Schaule
Stephanie G. C. Kroeze
Oliver Blanck
Susanne Stera
Klaus H. Kahl
Falk Roeder
Stephanie E. Combs
David Kaul
An Claes
Markus M. Schymalla
Sonja Adebahr
Franziska Eckert
Fabian Lohaus
Nasrin Abbasi-Senger
Guido Henke
Marcella Szuecs
Michael Geier
Nora Sundahl
Daniel Buergy
Reinhard Dummer
Matthias Guckenberger
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2020
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-020-01558-8

Other articles of this Issue 1/2020

Radiation Oncology 1/2020 Go to the issue

Research

Linac photon beam fine-tuning in PRIMO using the gamma-index analysis toolkit

Review

Fondazione Italiana Linfomi (FIL) expert consensus on the use of intensity-modulated and image-guided radiotherapy for Hodgkin’s lymphoma involving the mediastinum

Research

Radiation-induced lymphopenia correlates with survival in nasopharyngeal carcinoma: impact of treatment modality and the baseline lymphocyte count

Review

Recent advances in (chemo-)radiation therapy for rectal cancer: a comprehensive review

Research

Hippocampal changes in inflammasomes, apoptosis, and MEMRI after radiation-induced brain injury in juvenile rats

Review

Oncometabolites and the response to radiotherapy