OBJECTIVE: The aim of this review was to evaluate the existing evidence for radiotherapy for brain metastases in breast cancer patients and provide recommendations for the use of radiotherapy for brain metastases and leptomeningeal carcinomatosis.
METHODS: For the current review, a PubMed search was conducted including articles from 01/1985 to 05/2023. The search was performed using the following terms: (brain metastases OR leptomeningeal carcinomatosis) AND (breast cancer OR breast) AND (radiotherapy OR ablative radiotherapy OR radiosurgery OR stereotactic OR radiation).
CONCLUSIONS: Despite the fact that the biological subtype of breast cancer influences both the occurrence and relapse patterns of breast cancer brain metastases (BCBM), for most scenarios, no specific recommendations regarding radiotherapy can be made based on the existing evidence. For a limited number of BCBM (1-4), stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (SRT) is generally recommended irrespective of molecular subtype and concurrent/planned systemic therapy. In patients with 5-10 oligo-brain metastases, these techniques can also be conditionally recommended. For multiple, especially symptomatic BCBM, whole-brain radiotherapy (WBRT), if possible with hippocampal sparing, is recommended. In cases of multiple asymptomatic BCBM (≥ 5), if SRS/SRT is not feasible or in disseminated brain metastases (> 10), postponing WBRT with early reassessment and reevaluation of local treatment options (8-12 weeks) may be discussed if a HER2/Neu-targeting systemic therapy with significant response rates in the central nervous system (CNS) is being used. In symptomatic leptomeningeal carcinomatosis, local radiotherapy (WBRT or local spinal irradiation) should be performed in addition to systemic therapy. In patients with disseminated leptomeningeal carcinomatosis in good clinical condition and with only limited or stable extra-CNS disease, craniospinal irradiation (CSI) may be considered. Data regarding the toxicity of combining systemic therapies with cranial and spinal radiotherapy are sparse. Therefore, no clear recommendations can be given, and each case should be discussed individually in an interdisciplinary setting.

Thoracic radiation therapy (TRT) and prophylactic cranial irradiation (PCI) are commonly used in the management of extensive-stage small-cell lung cancer (ES-SCLC); however, Phase III trials of first-line immunotherapy often excluded these options. Guidance is needed regarding appropriate use of TRT, PCI, and magnetic resonance imaging (MRI) surveillance while new data are awaited.
In two web-based meetings, a pan-Canadian expert working group of five radiation oncologists and four medical oncologists addressed eight clinical questions regarding use of radiation therapy (RT) and MRI surveillance among patients with ES-SCLC receiving immunotherapy. A targeted literature review was conducted using PubMed and conference proceedings to identify recent (January 2019-April 2022) publications in this setting. Fifteen recommendations were developed; online voting was conducted to gauge agreement with each recommendation.
After considering recently available evidence across lung cancer populations and clinical experience, the experts recommended that all patients with a response to chemo-immunotherapy, good performance status (PS), and limited metastases be considered for consolidation TRT (e.g., 30 Gy in 10 fractions). When considered appropriate after multidisciplinary team discussion, TRT can be initiated during maintenance immunotherapy. All patients who respond to concurrent chemo-immunotherapy should undergo restaging with brain MRI to guide decision-making regarding PCI versus MRI surveillance alone. MRI surveillance should be conducted for two years after response to initial therapy. PCI (e.g., 25 Gy in 10 fractions or 20 Gy in 5 fractions) can be considered for patients without central nervous system involvement who have a response to chemo-immunotherapy and good PS. Concurrent treatment with PCI and immunotherapy or with TRT, PCI, and immunotherapy is appropriate after completion of initial therapy. All recommendations were agreed upon unanimously.
These consensus recommendations provide practical guidance regarding appropriate use of RT and immunotherapy in ES-SCLC while awaiting new clinical trial data.

There is insufficient evidence to support stroke prevention guidelines for childhood cancer survivors (CCS) treated with cranial irradiation for CNS tumors or other childhood cancers involving the CNS. We used a systematic consensus-building methodology to develop expert recommendations and define areas of controversy in managing asymptomatic CCS at risk for stroke.
A Delphi process was used to query a multispecialty panel of 45 physicians from the United States/Canada, with expertise in CCS, about their stroke screening and management practices (imaging, referrals, laboratory testing, and medications). Three iterative rounds of anonymous, scenario-based questionnaires, building on panelists\' aggregate responses, were used to reach consensus (≥90% agreement), agreement (89%-70% agree), or to understand the rationale for disagreement (<70% agree).
All 45 physicians participated in the first 2 rounds and 44 in the third. Panelists reached consensus on indications for referral to neurology and laboratory screening for modifiable cerebral vascular disease (CVD) risk factors in most scenarios. Panelists agreed that aspirin therapy is not recommended in the scenario of normal neuroimaging (86% agreed). Decisions about aspirin therapy in scenarios with abnormal neuroimaging were deferred to specialists; almost all agreed with not using aspirin for cavernomas with no evidence for previous hemorrhage (93%) and using aspirin for both large vessel CVD (93%) and small vessel CVD with evidence of previous stroke (86%). Clinical decisions that remain controversial (less than 70% agreement) include neuroimaging to screen asymptomatic CCS for CVD, referral to neurology for cavernomas, aspirin use in the setting of cavernomas with previous hemorrhage, or with evidence for small vessel CVD and no previous stroke, and indications for statins. Overall, pediatric neurologists/neuro-oncologists and radiation oncologists were more likely to advocate for screening and interventions.
Despite lack of evidence to guide the management of CCS at risk for stroke, expert recommendations and rationale developed by consensus methodology are helpful to support clinical decision-making.

暂无摘要。

OBJECTIVE: American Society of Radiation Oncology (ASTRO) has developed a guideline on appropriate radiation therapy for brain metastases. ASCO has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations.
METHODS: \"Radiation Therapy for Brain Metastases: An ASTRO Clinical Practice Guideline\"2 was reviewed for developmental rigor by methodologists. An ASCO Endorsement Panel subsequently reviewed the content and the recommendations.
RESULTS: The ASCO Endorsement Panel determined that the recommendations from the ASTRO guideline, published May 6, 2022, are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorses \"Radiation Therapy for Brain Metastases: An ASTRO Clinical Practice Guideline.\"2.
CONCLUSIONS: Within the guideline, stereotactic radiosurgery (SRS) is recommended for patients with Eastern Cooperative Oncology Group performance status of 0-2 and up to four intact brain metastases, and conditionally recommended for patients with up to 10 intact brain metastases. The guideline provides detailed dosing and fractionation recommendations on the basis of the size of the metastases. For patients with resected brain metastases, radiation therapy (SRS or whole-brain radiation therapy [WBRT]) is recommended to improve intracranial disease control; if there are limited additional brain metastases, SRS is recommended over WBRT. For patients with favorable prognosis and brain metastases ineligible for surgery and/or SRS, WBRT is recommended with hippocampal avoidance where possible and the addition of memantine is recommended. For patients with brain metastases, limiting the single-fraction V12Gy to brain tissue to ≤ 10 cm3 is conditionally recommended.Additional information is available at www.asco.org/neurooncology-guidelines.

The purpose of this critical review is to summarize the literature specific to single-fraction stereotactic radiosurgery (SRS) and multiple-fraction stereotactic radiation therapy (SRT) for postoperative brain metastases resection cavities and to present practice recommendations on behalf of the ISRS.
The Medline and Embase databases were used to apply the Preferred Reporting Items for Systematic Reviews and Meta-Analyses approach to search for manuscripts reporting SRS/SRT outcomes for postoperative brain metastases tumor bed resection cavities with a search end date of July 20, 2018. Prospective studies, consensus guidelines, and retrospective series that included exclusively postoperative brain metastases and had at minimum 100 patients were considered eligible.
The Embase search revealed 157 manuscripts, of which 77 were selected for full-text screening. PubMed yielded 55 manuscripts, of which 23 were selected for full text screening. We deemed 8 retrospective series, 1 phase 2 prospective study, 3 randomized controlled trials, and 1 consensus contouring paper appropriate for inclusion. The data suggest that SRS/SRT to surgical cavities with prescription doses of 30 to 50 Gy equivalent effective dose (EQD) 210, 50 to 70 Gy EQD25, and 70 to 90 EQD22 are associated with rates of local control ranging from 60.5% to 91% (median, 80.5%). Randomized data suggest improved local control with single-fraction SRS compared with observation and improved cognitive outcomes compared with whole-brain radiation therapy (WBRT). The toxicity of SRS/SRT in the postoperative setting was limited and is reviewed herein.
Although randomized data raise concern for poorer local control after resection cavity SRS than WBRT, these findings may be driven by factors such as conservative prescription doses used in the SRS arm. Retrospective studies suggest high rates of local control after single-fraction SRS and hypofractionated SRT for postoperative brain metastases. With a superior neurocognitive profile and no survival disadvantage to withholding WBRT, the ISRS recommends SRS as first-line treatment for eligible postoperative patients. Emerging data suggest that fractionated SRT may provide superior local control compared with single-fraction SRS, in particular, for large tumor cavity volumes/diameters and potentially for patients with a preoperative diameter greater than 2.5 cm.

Please see the full-text version of this guideline https://www.cns.org/guidelines/guidelines-treatment-adults-metastatic-brain-tumors/chapter_2) for the target population of each recommendation listed below.  SURGERY FOR METASTATIC BRAIN TUMORS AT NEW DIAGNOSIS QUESTION: Should patients with newly diagnosed metastatic brain tumors undergo surgery, stereotactic radiosurgery (SRS), or whole brain radiotherapy (WBRT)?
Level 1: Surgery + WBRT is recommended as first-line treatment in patients with single brain metastases with favorable performance status and limited extracranial disease to extend overall survival, median survival, and local control. Level 3: Surgery plus SRS is recommended to provide survival benefit in patients with metastatic brain tumors Level 3: Multimodal treatments including either surgery + WBRT + SRS boost or surgery + WBRT are recommended as alternatives to WBRT + SRS in terms of providing overall survival and local control benefits.  SURGERY AND RADIATION FOR METASTATIC BRAIN TUMORS QUESTION: Should patients with newly diagnosed metastatic brain tumors undergo surgical resection followed by WBRT, SRS, or another combination of these modalities?
Level 1: Surgery + WBRT is recommended as superior treatment to WBRT alone in patients with single brain metastases. Level 3: Surgery + SRS is recommended as an alternative to treatment with SRS alone to benefit overall survival. Level 3: It is recommended that SRS alone be considered equivalent to surgery + WBRT.  SURGERY FOR RECURRENT METASTATIC BRAIN TUMORS QUESTION: Should patients with recurrent metastatic brain tumors undergo surgical resection?
Level 3: Craniotomy is recommended as a treatment for intracranial recurrence after initial surgery or SRS.  SURGICAL TECHNIQUE AND RECURRENCE QUESTION A: Does the surgical technique (en bloc resection or piecemeal resection) affect recurrence?
Level 3: En bloc tumor resection, as opposed to piecemeal resection, is recommended to decrease the risk of postoperative leptomeningeal disease when resecting single brain metastases.
Does the extent of surgical resection (gross total resection or subtotal resection) affect recurrence?
Level 3: Gross total resection is recommended over subtotal resection in recursive partitioning analysis class I patients to improve overall survival and prolong time to recurrence. The full guideline can be found at https://www.cns.org/guidelines/guidelines-treatment-adults-metastatic-brain-tumors/chapter_2.

Should patients with brain metastases receive chemotherapy in addition to whole brain radiotherapy (WBRT) for the treatment of their brain metastases?
This recommendation applies to adult patients with newly diagnosed brain metastases amenable to both chemotherapy and radiation treatment.
Level 1: Routine use of chemotherapy following WBRT for brain metastases is not recommended. Level 3: Routine use of WBRT plus temozolomide is recommended as a treatment for patients with triple negative breast cancer.
Should patients with brain metastases receive chemotherapy in addition to stereotactic radiosurgery (SRS) for the treatment of their brain metastases?
Level 1: Routine use of chemotherapy following SRS is not recommended. Level 2: SRS is recommended in combination with chemotherapy to improve overall survival and progression free survival in lung adenocarcinoma patients.
Should patients with brain metastases receive chemotherapy alone?
Level 1: Routine use of cytotoxic chemotherapy alone for brain metastases is not recommended as it has not been shown to increase overall survival.Please see the full-text version of this guideline (https://www.cns.org/guidelines/guidelines-treatment-adults-metastatic-brain-tumors/chapter_5) for the target population of each recommendation.

Adult patients (older than 18 yr of age) with newly diagnosed brain metastases.
If whole brain radiation therapy (WBRT) is used, is there an optimal dose/fractionation schedule?
Level 1:  A standard WBRT dose/fractionation schedule (ie, 30 Gy in 10 fractions or a biological equivalent dose [BED] of 39 Gy10) is recommended as altered dose/fractionation schedules do not result in significant differences in median survival or local control. Level 3: Due to concerns regarding neurocognitive effects, higher dose per fraction schedules (such as 20 Gy in 5 fractions) are recommended only for patients with poor performance status or short predicted survival. Level 3: WBRT can be recommended to improve progression-free survival for patients with more than 4 brain metastases.
What impact does tumor histopathology or molecular status have on the decision to use WBRT, the dose fractionation scheme to be utilized, and its outcomes?
There is insufficient evidence to support the choice of any particular dose/fractionation regimen based on histopathology. Molecular status may have an impact on the decision to delay WBRT in subgroups of patients, but there is not sufficient data to make a more definitive recommendation.
Separate from survival outcomes, what are the neurocognitive consequences of WBRT, and what steps can be taken to minimize them?
Level 2: Due to neurocognitive toxicity, local therapy (surgery or SRS) without WBRT is recommended for patients with ≤4 brain metastases amenable to local therapy in terms of size and location. Level 2:  Given the association of neurocognitive toxicity with increasing total dose and dose per fraction of WBRT, WBRT doses exceeding 30 Gy given in 10 fractions, or similar biologically equivalent doses, are not recommended, except in patients with poor performance status or short predicted survival. Level 2: If prophylactic cranial irradiation (PCI) is given to prevent brain metastases for small cell lung cancer, the recommended WBRT dose/fractionation regimen is 25 Gy in 10 fractions, and because this can be associated with neurocognitive decline, patients should be told of this risk at the same time they are counseled about the possible survival benefits. Level 3: Patients having WBRT (given for either existing brain metastases or as PCI) should be offered 6 mo of memantine to potentially delay, lessen, or prevent the associated neurocognitive toxicity.
Does the addition of WBRT after surgical resection or radiosurgery improve progression-free or overall survival outcomes when compared to surgical resection or radiosurgery alone?
Level 2: WBRT is not recommended in WHO performance status 0 to 2 patients with up to 4 brain metastases because, compared to surgical resection or radiosurgery alone, the addition of WBRT improves intracranial progression-free survival but not overall survival. Level 2: In WHO performance status 0 to 2 patients with up to 4 brain metastases where the goal is minimizing neurocognitive toxicity, as opposed to maximizing progression-free survival and overall survival, local therapy (surgery or radiosurgery) without WBRT is recommended. Level 3: Compared to surgical resection or radiosurgery alone, the addition of WBRT is not recommended for patients with more than 4 brain metastases unless the metastases\' volume exceeds 7 cc, or there are more than 15 metastases, or the size or location of the metastases are not amenable to surgical resection or radiosurgery.The full guideline can be found at: https://www.cns.org/guidelines/guidelines-treatment-adults-metastatic-brain-tumors/chapter_3.

Childhood, adolescent, and young adult (CAYA) cancer survivors treated with platinum-based drugs, head or brain radiotherapy, or both have an increased risk of ototoxicity (hearing loss, tinnitus, or both). To ensure optimal care and reduce consequent problems-such as speech and language, social-emotional development, and learning difficulties-for these CAYA cancer survivors, clinical practice guidelines for monitoring ototoxicity are essential. The implementation of surveillance across clinical settings is hindered by differences in definitions of hearing loss, recommendations for surveillance modalities, and remediation. To address these deficiencies, the International Guideline Harmonization Group organised an international multidisciplinary panel, including 32 experts from ten countries, to evaluate the quality of evidence for ototoxicity following platinum-based chemotherapy and head or brain radiotherapy, and formulate and harmonise ototoxicity surveillance recommendations for CAYA cancer survivors.