Letter to the Editor Regarding Effects of the COVID-19 Outbreak in Northern Italy: Perspectives from the Bergamo Neurosurgery Department, and the role of Radiosurgery as a minimally invasive procedure in the pandemic outbreak. Physician scientists around the world are working against COVID-19 and continuation of less invasive brain oncology treatments demands actions now [2, 8] . The effects of the COVID-19 Outbreak in Northern Italy and the perspectives from the Bergamo Neurosurgery Department has been described by Bernucci et al [2] , and we are writing to advocate for the use of minimally invasive urgent procedures and gamma knife radiosurgery (GKRS) as a first-line and/or palliative treatment in brain tumors, in specific, in primary central nervous system lymphoma (PCNSL) [1, 7] .
COVID-19 is extremely infectious as described in the article all hospitalizations for elective surgical procedures were stopped in Italy 2 , and actually currently, worldwide, in special for elderly population [8, 9] . The pandemic has changing our life radically, nations are working at home, mass transportation is shutting down, main central towns and worldwide cities are doomed [5] . Medicine practicing is shifting too, since many clinical providers and clinical resources are isolated and specifically dedicated to the Covid-19 worldwide emergency [5, 8] . Although neurooncological treatment is changing in senior population, avoiding prompt chemotherapy treatment and open surgery and or invasive procedures in most cases could be a challenge [3] . Wheatear possible invasive procedures should be delayed in COVID-19 era. Surgical procedures may induce the immune response and may increase the risk of rising severe acute respiratory disease in Covid-19 patients) [5] . Additionally, open approach should be avoided in order to reduce length of hospital stay and potential postoperative morbidity, thus reducing inhospital spread of nosocomial infections and Covid-19 ) [1, 5, 9] .
In a recent systematic review analyzing current clinical studies in Primary CNS Lymphoma and in a Level III, single center, retrospective, nonrandomized observational study, the authors found that life expectancy and patient-reported outcomes were found to be superior at 3-year follow-up when using GKRS combined with methotrexate (MTX) compared with MTX only [7] . Although concerns have been raised regarding the use of GKRS, a systematic review published in this year provides support for use of radiosurgery when encountering the challenging situation of multiple patient comorbidities and the inability to proceed with chemotherapy due to systemic instability or the inability to receive in-patient medical treatment due to COVID-19 outbreak [9] .
Standard treatment (ST) for PCNSL consists of different methotrexate-based chemotherapy regimens associated with whole brain radiotherapy (WBRT) [2] [3] [4] .
Unfortunately, ST requires high-dosage regimens that can result in methotrexate toxicity and a broad range of serious side-effects, especially in elderly or immunocompromised patients [1] . Additional concerns have been noted for the use of WBRT. Increasingly, research has demonstrated the hazards of using WBRT [4, 6] . Several studies and a recent systematic review have demonstrated that in patients diagnosed with PCNSL with multiple lesions (> 5) there is a significantly higher rate of complications, especially in senior patients, due to chemotherapy and radiotherapy side effects [4, 7] .
Concordantly, GKRS has proven to be an effective therapeutic option for the treatment of brain tumors, including both single and multiple smaller brain metastases 5 .
The technique results in a reduction of adverse patient events as well as an increased ability to attack surgically inaccessible lesions and achieve local tumor control [1] . demonstrated that the use of GKRS as a rescue therapy could enhance treatment outcomes for patients. In this study 14 patients that had relapsed or were refractory to salvage SRS, experienced local control of 95%, 91%, and 75% at 3, 6, and 12 months post-SRS [9] . Collectively, this data supports the use of GKRS as a viable treatment for adults diagnosed with PCNSL. However, several questions remain to be answered including what outcomes can be achieved through the use of GKRS in patients that have developed PCNSL due to HIV [1, 7] . Immunocompromised patients have consistently been shown to have the highest mortality rates when provided with all existing treatments and significantly higher adverse events with the use of whole-brain radiation and/or methotrexate [5, 6] . Neurosurgeons and oncologists have a responsibility to utilize existing evidence-based information to improve the treatment outcomes and quality of life of these patients. In the Infectious disease outbreaks such as COVID-19, providing counseling and information for potentially utilizing GKRS as a first-line treatment option in PCNSL is clearly warranted in light of this evidence, and minimize the compromise of social distancing during cancer care delivery.