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Are there still indications for whole brain irradiation in 2021?

Are there still indications for whole brain irradiation in 2021? short review memo (2021) 14:204–207 https://doi.org/10.1007/s12254-021-00710-8 Karin Dieckmann · Harald Herrmann Received: 7 April 2021 / Accepted: 10 April 2021 / Published online: 7 May 2021 © The Author(s) 2021 Summary Brain metastases (BM) are the most fre- nosed symptomatic and asymptomatic BMs contin- quent intracranial tumors in adults. About 10–20% ues to increase. Historically, all patients with multi- of the patients with cancer will develop them. His- ple BMs were treated with whole brain radiotherapy torically, most of the patients with brain metastases (WBRT). The goal of WBRT was symptom reduction were treated with whole brain radiotherapy (WBRT). and palliation, to stop brain metastases progression The intention was to control the metastases and to and possibly to prolong overall survival (OS). However, eliminate distant micrometastases. Randomized con- neurocognitive functional decline has been reported trol trials showed no difference in survival in patients in 31–57% of the patients at 3 months and 48–89% at with single and oligometastases treated with WBRT 1 year after WBRT [1]. compared with stereotactic radiosurgery (SRS). To In order to maintain neurocognitive function, avoid treatment-related toxicities with neurocognitive stereotactic radiosurgery (SRS) and fractionated stereo- decline, indications for WBRT are changing. High pre- tactic radiosurgery (fSRS) have been implemented in cision therapy with SRS or postoperative stereotactic the treatment of patients in recent years. This was treatments have become increasingly important. Only not only performed in patients with a single metas- in exceptional cases is WBRT still the treatment of tasis, but also in patients with brain oligometastases, choice. despite the higher risk of new intracranial relapses. Modern treatment techniques such as volumetric Keywords Brain metastasis · Neurocognitive modulated arc therapy (VMAT) allow for WBRT with impairment · Whole brain radiotherapy · Stereotactic hippocampal-avoidance and dose-escalation with radiotherapy oligometastases [12, 14, 15]. In a randomized double- blind, placebo-controlled phase III trial (RTOG 0614), the use of memantine, a neuroprotective compound, Introduction during and after WBRT has resulted in better cognitive The management of brain metastases (BM) is very function over time [24]. complex. The performance status of the patient, lo- Traditional chemotherapy has played a limited role cal and distant control of the primary tumor and co- in the management of BM. However, recent advances morbidities have to be taken into account. Most fre- in targeted therapy and checkpoint inhibitors have quently BMs are diagnosed in patients with lung can- improved survival in patients with BM. Modern sys- cer (20–56% of all BMs), breast cancer (5–20%) and temic treatments as tyrosine kinase inhibitors (TKI) melanoma (7–16%) accounting for 70–80% of all brain and immunotherapies can cross the blood–brain bar- metastases [9–11]. rier and have improved the results of systemic treat- Based on magnetic resonance imaging (MRI) as the ment in patients with asymptomatic disease [7]. standard diagnostic tool, the number of newly diag- In the modern era, therefore, a personalized treat- ment decision for patients with BMs has to be per- formed. To choose an adequate treatment, scores K. Dieckmann ()· H. Herrmann such as the graded prognostic assessment (GPA score) Department of Radio-Oncology, Medical University of and the recursive partitioning analysis (RPA) includ- Vienna, Waehringer Guertel 18–20, 1090 Vienna, Austria karin.dieckmann@meduniwien.ac.at ing prognostic factors as histology of the primary tu- 204 Are there still indications for whole brain irradiation in 2021? K short review mor, the target mutation status, age of the patient, which kind of combination is performed WBRT in- Karnofsky performance score (KPS), number and vol- creases the risk of neurocognitive decline, transient ume of the metastases with or without neurological lower physical functioning and more fatigue. Based symptoms, and the extra cranial tumor extension and on these results, the American Society for Radiation activity are required [23]. Oncology (ASTRO) does not recommend a combi- nation of SRS and WBRT routinely in patients with limited BMs, but to perform frequent MRI surveil- WBRT as first choice of treatment in patients lance. with brain metastases from solid tumors WBRT was the standard treatment for most patients WBRT in patients with leptomeningeal with BM. Today WBRT is indicated for patients with carcinomatosis poor prognosis if BM are unsuitable for radiosurgery or surgery. According to the European Association of Palliative indications for WBRT are leptomeningeal Neuro-Oncology (EANO) guidelines on brain metas- carcinomatoses (LC) with multifocal spread of tumor tases from solid tumors, WBRT in combination with cells and/or cerebrospinal fluid (EANO-ESMO guide- corticosteroids is recommended in patients with lines) and eventually concomitant cerebral lesions. (a) multiple brain metastases or presenting with The incidence is approximately 5–10% of patients (b) uncontrolled primary tumor or (c) multiple ex- presenting with metastatic disease [17, 18]. In these tracerebral metastases, if they are symptomatic [7]. patients WBRT can delay neurologic deterioration Upfront WBRT remains a standard approach for pa- withoutanincreaseinOS. tients with multiple brain metastases even though the Quality of Life after Treatment for Brain Metas- WBRT as prophylactic cranial irradiation tases (QUARTZ) trial cannot assert the advantage of WBRT plus best supportive care compared with best Prophylactic cranial irradiation (PCI) in small cell lung supportive care alone in patients [19]. cancer (SCLC) is still the gold standard for patients Median survival following WBRT alone ranges from with limited tumor progression or with very good 3 to 6 months, with 10–15% of patients alive at 1 year treatment response and stable extracranial disease [8]. Various fractionation schedules may be used after chemotherapy. Auperin et al. in 1999 performed (30 Gy in 10 daily fractions, 20 Gy in 4 or 5 daily frac- a meta-analysis of 7 studies comprising 987 patients. tions, or others). None has proven superiority in They found that PCI showed an improvement in the terms of prolonging OS or better neurologic function 3-year OS of 5.4% (15.3% to 20.7%) [22]. The re- or symptom control described in a meta-analysis of sults of this meta-analysis could not be confirmed in 39 trials by Tsao et al. [25]. a prospective MRI-based phase III study by Takahashi et al. [16]. New treatment concepts are under evalua- tion recommending close monitoring by MRI controls WBRT in patients with recurrent brain metastases in compliant patients and local SRS in case of single after preliminary SRS or oligometastases. Salvage WBRT can be an option in patients with fa- vorable prognostic factors and recurrence of multiple Patients with asymptomatic brain metastases new brain metastases relatively long time after SRS, who are not suitable for new SRS. No prospective Staging of the brain at the time of diagnosis is the studies are available, but salvage SRS after WBRT has gold standard for patients with solid tumors. Many been widely performed. clinically asymptomatic patients may have BMs de- tected by MRI. According to the recommendations of the EANO Guidelines [7], conventional chemotherapy WBRT in combination with SRS or surgery may be the initial treatment for patients with BM from WBRT leads to an improved outcome in patients with chemosensitive tumors like SCLC and breast cancer. single metastases, including improved overall survival, Patients with brain metastases from NSCLC harboring less development of new brain relapses and longer activating EGFR mutations or ALK rearrangement can duration of functional independence [3–5]. Patients benefit from specific TKIs or patients with HER2-pos- with brain oligometastases (1–4 metastases) showed itive breast cancer can benefit from lapatinib alone or no improvement with combined treatment of WBRT in combination with capecitabine. A benefit of ipili- and SRS. Studies compared WBRT plus SRS with SRS mumab or BRAF inhibitors on BM of melanomas has alone [6]. Overall survival after combined treatment been frequently reported in the literature. did not differ from SRS alone, only the distant brain The response rate to targeted therapies and im- metastases were more frequent in patients treated munotherapies seems to be higher than those ob- with SRS alone. Adjuvant WBRT following surgery served after chemotherapy. Currently new generations increases local control and reduces distant relapses of small molecule inhibitors are under evaluation. In in patients with brain metastases > 3 cm. Regardless case of good response of asymptomatic BMs WBRT or K Are there still indications for whole brain irradiation in 2021? 205 short review 5. Andrews DW, Scott CB, Sperduto PW, et al. Whole brain SRS can be postponed or completely avoided. Prereq- radiation therapy with or without stereotactic radiosurgery uisite for this procedure is close MRI monitoring to boost for patients with oneto threebrain metastases: phase detect growing BMs as soon as possible. III results of the RTOG 9508 randomised trial. Lancet. Systemic targeted therapies have become a more 2004;363:1665–72. important part of BM treatment especially in patients 6. Aoyama H, Shirato H, Tago M, et al. Stereotactic radio- with asymptomatic or oligosymptomatic disease. surgery plus whole-brain radiation therapy vs stereotactic radiosurgeryalonefortreatmentofbrainmetastases: aran- domizedcontrolledtrial. JAMA. 2006;295:2483–91. Conclusion 7. Soffietti R, Abacioglu U, Baumert B, et al. Diagnosis and treatment of brain metastases from solid tumors: Radiotherapy still plays a major role, as the activity guidelines fromtheEuropean Association of Neuro-Oncol- of systemic chemotherapy within brain parenchyma ogy(EANO).NeuroOncol. 2017Feb1;19(2):162–74. remains limited [2]. WBRT does not prevent the de- 8. Li J, Bentzen SM, Renschler M, etal. Regression after whole- velopment of new BMs and has a limited influence brainradiationtherapyforbrainmetastasescorrelateswith survival and improved neurocognitive function. J Clin on overall survival. It can lead to decline of neu- Oncol. 2007;25(10):1260–6. https://doi.org/10.1200/JCO. rocognitive function and quality of life. Therefore, 2006.09.2536. new local treatment options as SRS and fSRS have re- 9. NayakL,LeeEQ,WenPY.Epidemiologyofbrainmetastases. placed WBRT in single and oligometastases. Only in CurrOncolRep. 2012;14(1):48–54. case of multiple BMs unsuitable for SRS or surgery 10. Barnholtz-Sloan JS, Sloan AE, Davis FG, Vigneau FD, Lai P, and in patients with poor prognosis, is WBRT the Sawaya RE. Incidence proportions of brain metastases treatment of choice. New medical therapies passing in patients diagnosed (1973 to 2001) in the metropoli- tan Detroit cancer surveillance system. J Clin Oncol. the blood–brain barrier (BBB) may allow to postpone 2004;22(14):2865–72. WBRT in asymptomatic patients and may inhibit the 11. Berghoff AS, Schur S, Füreder LM, et al. Descriptive neurocognitive decline and maintain the quality-of- statistical analysis of a real life cohort of 2419 patients life. with brain metastases of solid cancers. ESMO Open. 2016;1(2):e24. Funding Open access funding providedby Medical University 12. Sperduto PW, Berkey B, Gaspar LE, Mehta M, Curran W. of Vienna. A new prognostic index and comparison to three other Conflict of interest K. Dieckmann and H. Herrmann declare indices for patients with brain metastases: an analysis of that they have no competing interests. 1,960 patients in the RTOGdatabase. Int J Radiat Oncol Biol Phys. 2008;70(2):510–4. Open Access This article is licensed under a Creative Com- 13. Lauko A, Rauf Y, Ahluwalia MS. Medical management of mons Attribution 4.0 International License, which permits brainmetastases. NeuroOncolAdv. 2020;2(1):1–14. use, sharing, adaptation, distribution and reproduction in 14. Gondi V,Deshmukh S,Brown PD, et al. NRG oncol- any medium or format, as long as you give appropriate credit ogy CC001: a phase III trial of hippocampal avoidance to the original author(s) and the source, provide a link to (HA) in addition to whole-brain radiotherapy (WBRT) plus the Creative Commons licence, and indicate if changes were memantine to preserve neurocognitive function (NCF) made. The images or other third party material in this article in patients with brain metastases (BM). J Clin Oncol. are included in the article’s Creative Commons licence, unless 2019;37(15_suppl):2009–2009. https://doi.org/10.1200/ indicated otherwise in a credit line to the material. If material JCO.2019.37.15_suppl.2009. is not included in the article’s Creative Commons licence and 15. GondiV,Deshmukh S,Brown PD,et al. Preservation of your intended use is not permitted by statutory regulation or neurocognitive function with conformal avoidance of the exceeds the permitted use, you will need to obtain permis- hippocampus during wholebrain radiotherapy for brain sion directly from the copyright holder. To view a copy of this metastases: preliminary results of phase III trial NRG licence, visit http://creativecommons.org/licenses/by/4.0/. Oncology CC001 [Abstract]. 2018 Annual Meeting ASTRO AbstractLBA9. 2018. 16. Takahashi T, Yamanaka T, Seto T, et al. Prophylactic cranial References irradiation versus observation in patients with extensive- disease small-cell lung cancer: a multicentre, randomised, 1. Tallet AV, Azria D, Barlesi F, Spano JP, Carpentier AF, open-label,phase3trial. LancetOncol. 2017;18(5):663–71. Gonçalves A, et al. Neurocognitive function impairment 17. Le Rhun E, Weller M, Brandsma D, Van den Bent M, de after whole brain radiotherapy for brain metastases: actual Azambuja E, Henriksson R, et al. EANO-ESMO clinical assessment. Radiat Oncol. 2012;7:77. https://doi.org/10. practice guidelines for diagnosis, treatment and follow- 1186/1748-717X-7-77. up of patients with leptomeningeal metastasis from solid 2. Khuntia D, Brown P, Li J, et al. Whole-brain radiotherapy tumours. AnnOncol. 2017;28:iv84–iv99. in the management of brain metastasis. J Clin Oncol. 18. El ShafieRA, BöhmK, Weber D, etal. Palliativeradiotherapy 2006;24:1295–304. for leptomeningeal carcinomatosis—analysis of outcome, 3. PatchellRA,TibbsPA,WalshJW,etal. Arandomizedtrialof prognostic factors, and symptom response. Front Oncol. surgery in the treatment of single metastases to the brain. 2019;8:641. NEnglJMed. 1990;322:494–500. 19. Mulvenna P, Nankivell M, Barton R, et al. Dexamethasone 4. Shaw E, Scott C, Souhami L, et al. Single dose radiosurgical and supportive care with or without whole brain radiother- treatment of recurrent previously irradiated primary brain apy in treating patients with non-small cell lung cancer tumorsandbrainmetastases: finalreportofRTOGprotocol withbrainmetastasesunsuitableforresectionorstereotac- 90–05. IntJRadiatOncolBiolPhys. 2000;47:291–8. 206 Are there still indications for whole brain irradiation in 2021? K short review tic radiotherapy (QUARTZ): results from a phase 3, non- radiotherapy: a randomized, doubleblind, placebo-con- inferiority,randomisedtrial. Lancet. 2016;388:2004–14. trolledtrial. NeuroOncol. 2013;15(10):1429–37. 20. PercyAK,ElvebackLR,OkazakiH,KurlandLT.Neoplasmsof 25. TsaoMN,LloydN,WongRK,etal. Wholebrainradiotherapy the central nervous system. Epidemiologic considerations. for the treatment of newly diagnosed multiple brain metas- Neurology. 1972;22(1):40–8. tases. Cochrane Database Syst Rev. 2012; https://doi.org/ 21. Tsukada Y, Fouad A, Pickren JW, Lane WW. Central nervous 10.1002/14651858.CD003869.pub3. system metastasis from breast carcinoma. Autopsy study. Publisher’s Note Springer Nature remains neutral with regard Cancer. 1983;52(12):2349–54. to jurisdictional claims in published maps and institutional 22. Aupérin A, Arriagada R, Pignon JP,etal.Prophylactic cranial affiliations. irradiation for patients with small-cell lung cancer in com- plete remission. Prophylactic cranial irradiation overview collaborativegroup. NEnglJMed. 1999;341(7):476–84. 23. Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, Wasser- For latest news from interna- man T, et al. Recursive partitioning analysis (RPA) of tional oncology congresses see: prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol http://www.springermedizin.at/ BiolPhys. 1997;37:745–51. memo-inoncology 24. Radiation Therapy Oncology Group (RTOG), Brown PD, Pugh S, Laack NN, et al. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain K Are there still indications for whole brain irradiation in 2021? 207 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png memo - Magazine of European Medical Oncology Springer Journals

Are there still indications for whole brain irradiation in 2021?

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short review memo (2021) 14:204–207 https://doi.org/10.1007/s12254-021-00710-8 Karin Dieckmann · Harald Herrmann Received: 7 April 2021 / Accepted: 10 April 2021 / Published online: 7 May 2021 © The Author(s) 2021 Summary Brain metastases (BM) are the most fre- nosed symptomatic and asymptomatic BMs contin- quent intracranial tumors in adults. About 10–20% ues to increase. Historically, all patients with multi- of the patients with cancer will develop them. His- ple BMs were treated with whole brain radiotherapy torically, most of the patients with brain metastases (WBRT). The goal of WBRT was symptom reduction were treated with whole brain radiotherapy (WBRT). and palliation, to stop brain metastases progression The intention was to control the metastases and to and possibly to prolong overall survival (OS). However, eliminate distant micrometastases. Randomized con- neurocognitive functional decline has been reported trol trials showed no difference in survival in patients in 31–57% of the patients at 3 months and 48–89% at with single and oligometastases treated with WBRT 1 year after WBRT [1]. compared with stereotactic radiosurgery (SRS). To In order to maintain neurocognitive function, avoid treatment-related toxicities with neurocognitive stereotactic radiosurgery (SRS) and fractionated stereo- decline, indications for WBRT are changing. High pre- tactic radiosurgery (fSRS) have been implemented in cision therapy with SRS or postoperative stereotactic the treatment of patients in recent years. This was treatments have become increasingly important. Only not only performed in patients with a single metas- in exceptional cases is WBRT still the treatment of tasis, but also in patients with brain oligometastases, choice. despite the higher risk of new intracranial relapses. Modern treatment techniques such as volumetric Keywords Brain metastasis · Neurocognitive modulated arc therapy (VMAT) allow for WBRT with impairment · Whole brain radiotherapy · Stereotactic hippocampal-avoidance and dose-escalation with radiotherapy oligometastases [12, 14, 15]. In a randomized double- blind, placebo-controlled phase III trial (RTOG 0614), the use of memantine, a neuroprotective compound, Introduction during and after WBRT has resulted in better cognitive The management of brain metastases (BM) is very function over time [24]. complex. The performance status of the patient, lo- Traditional chemotherapy has played a limited role cal and distant control of the primary tumor and co- in the management of BM. However, recent advances morbidities have to be taken into account. Most fre- in targeted therapy and checkpoint inhibitors have quently BMs are diagnosed in patients with lung can- improved survival in patients with BM. Modern sys- cer (20–56% of all BMs), breast cancer (5–20%) and temic treatments as tyrosine kinase inhibitors (TKI) melanoma (7–16%) accounting for 70–80% of all brain and immunotherapies can cross the blood–brain bar- metastases [9–11]. rier and have improved the results of systemic treat- Based on magnetic resonance imaging (MRI) as the ment in patients with asymptomatic disease [7]. standard diagnostic tool, the number of newly diag- In the modern era, therefore, a personalized treat- ment decision for patients with BMs has to be per- formed. To choose an adequate treatment, scores K. Dieckmann ()· H. Herrmann such as the graded prognostic assessment (GPA score) Department of Radio-Oncology, Medical University of and the recursive partitioning analysis (RPA) includ- Vienna, Waehringer Guertel 18–20, 1090 Vienna, Austria karin.dieckmann@meduniwien.ac.at ing prognostic factors as histology of the primary tu- 204 Are there still indications for whole brain irradiation in 2021? K short review mor, the target mutation status, age of the patient, which kind of combination is performed WBRT in- Karnofsky performance score (KPS), number and vol- creases the risk of neurocognitive decline, transient ume of the metastases with or without neurological lower physical functioning and more fatigue. Based symptoms, and the extra cranial tumor extension and on these results, the American Society for Radiation activity are required [23]. Oncology (ASTRO) does not recommend a combi- nation of SRS and WBRT routinely in patients with limited BMs, but to perform frequent MRI surveil- WBRT as first choice of treatment in patients lance. with brain metastases from solid tumors WBRT was the standard treatment for most patients WBRT in patients with leptomeningeal with BM. Today WBRT is indicated for patients with carcinomatosis poor prognosis if BM are unsuitable for radiosurgery or surgery. According to the European Association of Palliative indications for WBRT are leptomeningeal Neuro-Oncology (EANO) guidelines on brain metas- carcinomatoses (LC) with multifocal spread of tumor tases from solid tumors, WBRT in combination with cells and/or cerebrospinal fluid (EANO-ESMO guide- corticosteroids is recommended in patients with lines) and eventually concomitant cerebral lesions. (a) multiple brain metastases or presenting with The incidence is approximately 5–10% of patients (b) uncontrolled primary tumor or (c) multiple ex- presenting with metastatic disease [17, 18]. In these tracerebral metastases, if they are symptomatic [7]. patients WBRT can delay neurologic deterioration Upfront WBRT remains a standard approach for pa- withoutanincreaseinOS. tients with multiple brain metastases even though the Quality of Life after Treatment for Brain Metas- WBRT as prophylactic cranial irradiation tases (QUARTZ) trial cannot assert the advantage of WBRT plus best supportive care compared with best Prophylactic cranial irradiation (PCI) in small cell lung supportive care alone in patients [19]. cancer (SCLC) is still the gold standard for patients Median survival following WBRT alone ranges from with limited tumor progression or with very good 3 to 6 months, with 10–15% of patients alive at 1 year treatment response and stable extracranial disease [8]. Various fractionation schedules may be used after chemotherapy. Auperin et al. in 1999 performed (30 Gy in 10 daily fractions, 20 Gy in 4 or 5 daily frac- a meta-analysis of 7 studies comprising 987 patients. tions, or others). None has proven superiority in They found that PCI showed an improvement in the terms of prolonging OS or better neurologic function 3-year OS of 5.4% (15.3% to 20.7%) [22]. The re- or symptom control described in a meta-analysis of sults of this meta-analysis could not be confirmed in 39 trials by Tsao et al. [25]. a prospective MRI-based phase III study by Takahashi et al. [16]. New treatment concepts are under evalua- tion recommending close monitoring by MRI controls WBRT in patients with recurrent brain metastases in compliant patients and local SRS in case of single after preliminary SRS or oligometastases. Salvage WBRT can be an option in patients with fa- vorable prognostic factors and recurrence of multiple Patients with asymptomatic brain metastases new brain metastases relatively long time after SRS, who are not suitable for new SRS. No prospective Staging of the brain at the time of diagnosis is the studies are available, but salvage SRS after WBRT has gold standard for patients with solid tumors. Many been widely performed. clinically asymptomatic patients may have BMs de- tected by MRI. According to the recommendations of the EANO Guidelines [7], conventional chemotherapy WBRT in combination with SRS or surgery may be the initial treatment for patients with BM from WBRT leads to an improved outcome in patients with chemosensitive tumors like SCLC and breast cancer. single metastases, including improved overall survival, Patients with brain metastases from NSCLC harboring less development of new brain relapses and longer activating EGFR mutations or ALK rearrangement can duration of functional independence [3–5]. Patients benefit from specific TKIs or patients with HER2-pos- with brain oligometastases (1–4 metastases) showed itive breast cancer can benefit from lapatinib alone or no improvement with combined treatment of WBRT in combination with capecitabine. A benefit of ipili- and SRS. Studies compared WBRT plus SRS with SRS mumab or BRAF inhibitors on BM of melanomas has alone [6]. Overall survival after combined treatment been frequently reported in the literature. did not differ from SRS alone, only the distant brain The response rate to targeted therapies and im- metastases were more frequent in patients treated munotherapies seems to be higher than those ob- with SRS alone. Adjuvant WBRT following surgery served after chemotherapy. Currently new generations increases local control and reduces distant relapses of small molecule inhibitors are under evaluation. In in patients with brain metastases > 3 cm. Regardless case of good response of asymptomatic BMs WBRT or K Are there still indications for whole brain irradiation in 2021? 205 short review 5. Andrews DW, Scott CB, Sperduto PW, et al. Whole brain SRS can be postponed or completely avoided. Prereq- radiation therapy with or without stereotactic radiosurgery uisite for this procedure is close MRI monitoring to boost for patients with oneto threebrain metastases: phase detect growing BMs as soon as possible. III results of the RTOG 9508 randomised trial. Lancet. Systemic targeted therapies have become a more 2004;363:1665–72. important part of BM treatment especially in patients 6. Aoyama H, Shirato H, Tago M, et al. Stereotactic radio- with asymptomatic or oligosymptomatic disease. surgery plus whole-brain radiation therapy vs stereotactic radiosurgeryalonefortreatmentofbrainmetastases: aran- domizedcontrolledtrial. JAMA. 2006;295:2483–91. Conclusion 7. Soffietti R, Abacioglu U, Baumert B, et al. Diagnosis and treatment of brain metastases from solid tumors: Radiotherapy still plays a major role, as the activity guidelines fromtheEuropean Association of Neuro-Oncol- of systemic chemotherapy within brain parenchyma ogy(EANO).NeuroOncol. 2017Feb1;19(2):162–74. remains limited [2]. WBRT does not prevent the de- 8. Li J, Bentzen SM, Renschler M, etal. Regression after whole- velopment of new BMs and has a limited influence brainradiationtherapyforbrainmetastasescorrelateswith survival and improved neurocognitive function. J Clin on overall survival. It can lead to decline of neu- Oncol. 2007;25(10):1260–6. https://doi.org/10.1200/JCO. rocognitive function and quality of life. Therefore, 2006.09.2536. new local treatment options as SRS and fSRS have re- 9. NayakL,LeeEQ,WenPY.Epidemiologyofbrainmetastases. placed WBRT in single and oligometastases. Only in CurrOncolRep. 2012;14(1):48–54. case of multiple BMs unsuitable for SRS or surgery 10. Barnholtz-Sloan JS, Sloan AE, Davis FG, Vigneau FD, Lai P, and in patients with poor prognosis, is WBRT the Sawaya RE. Incidence proportions of brain metastases treatment of choice. New medical therapies passing in patients diagnosed (1973 to 2001) in the metropoli- tan Detroit cancer surveillance system. J Clin Oncol. the blood–brain barrier (BBB) may allow to postpone 2004;22(14):2865–72. WBRT in asymptomatic patients and may inhibit the 11. Berghoff AS, Schur S, Füreder LM, et al. Descriptive neurocognitive decline and maintain the quality-of- statistical analysis of a real life cohort of 2419 patients life. with brain metastases of solid cancers. ESMO Open. 2016;1(2):e24. Funding Open access funding providedby Medical University 12. Sperduto PW, Berkey B, Gaspar LE, Mehta M, Curran W. of Vienna. A new prognostic index and comparison to three other Conflict of interest K. Dieckmann and H. Herrmann declare indices for patients with brain metastases: an analysis of that they have no competing interests. 1,960 patients in the RTOGdatabase. Int J Radiat Oncol Biol Phys. 2008;70(2):510–4. Open Access This article is licensed under a Creative Com- 13. Lauko A, Rauf Y, Ahluwalia MS. Medical management of mons Attribution 4.0 International License, which permits brainmetastases. NeuroOncolAdv. 2020;2(1):1–14. use, sharing, adaptation, distribution and reproduction in 14. Gondi V,Deshmukh S,Brown PD, et al. NRG oncol- any medium or format, as long as you give appropriate credit ogy CC001: a phase III trial of hippocampal avoidance to the original author(s) and the source, provide a link to (HA) in addition to whole-brain radiotherapy (WBRT) plus the Creative Commons licence, and indicate if changes were memantine to preserve neurocognitive function (NCF) made. The images or other third party material in this article in patients with brain metastases (BM). J Clin Oncol. are included in the article’s Creative Commons licence, unless 2019;37(15_suppl):2009–2009. https://doi.org/10.1200/ indicated otherwise in a credit line to the material. If material JCO.2019.37.15_suppl.2009. is not included in the article’s Creative Commons licence and 15. GondiV,Deshmukh S,Brown PD,et al. Preservation of your intended use is not permitted by statutory regulation or neurocognitive function with conformal avoidance of the exceeds the permitted use, you will need to obtain permis- hippocampus during wholebrain radiotherapy for brain sion directly from the copyright holder. To view a copy of this metastases: preliminary results of phase III trial NRG licence, visit http://creativecommons.org/licenses/by/4.0/. Oncology CC001 [Abstract]. 2018 Annual Meeting ASTRO AbstractLBA9. 2018. 16. Takahashi T, Yamanaka T, Seto T, et al. Prophylactic cranial References irradiation versus observation in patients with extensive- disease small-cell lung cancer: a multicentre, randomised, 1. Tallet AV, Azria D, Barlesi F, Spano JP, Carpentier AF, open-label,phase3trial. LancetOncol. 2017;18(5):663–71. Gonçalves A, et al. Neurocognitive function impairment 17. Le Rhun E, Weller M, Brandsma D, Van den Bent M, de after whole brain radiotherapy for brain metastases: actual Azambuja E, Henriksson R, et al. EANO-ESMO clinical assessment. Radiat Oncol. 2012;7:77. https://doi.org/10. practice guidelines for diagnosis, treatment and follow- 1186/1748-717X-7-77. up of patients with leptomeningeal metastasis from solid 2. Khuntia D, Brown P, Li J, et al. Whole-brain radiotherapy tumours. AnnOncol. 2017;28:iv84–iv99. in the management of brain metastasis. J Clin Oncol. 18. El ShafieRA, BöhmK, Weber D, etal. Palliativeradiotherapy 2006;24:1295–304. for leptomeningeal carcinomatosis—analysis of outcome, 3. PatchellRA,TibbsPA,WalshJW,etal. Arandomizedtrialof prognostic factors, and symptom response. Front Oncol. surgery in the treatment of single metastases to the brain. 2019;8:641. NEnglJMed. 1990;322:494–500. 19. Mulvenna P, Nankivell M, Barton R, et al. Dexamethasone 4. Shaw E, Scott C, Souhami L, et al. Single dose radiosurgical and supportive care with or without whole brain radiother- treatment of recurrent previously irradiated primary brain apy in treating patients with non-small cell lung cancer tumorsandbrainmetastases: finalreportofRTOGprotocol withbrainmetastasesunsuitableforresectionorstereotac- 90–05. IntJRadiatOncolBiolPhys. 2000;47:291–8. 206 Are there still indications for whole brain irradiation in 2021? K short review tic radiotherapy (QUARTZ): results from a phase 3, non- radiotherapy: a randomized, doubleblind, placebo-con- inferiority,randomisedtrial. Lancet. 2016;388:2004–14. trolledtrial. NeuroOncol. 2013;15(10):1429–37. 20. 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Journal

memo - Magazine of European Medical Oncology – Springer Journals

Published: Jun 1, 2021

Keywords: oncology; medicine/public health, general

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