Small cell lung cancer (SCLC) outcomes remain poor. Approximately, 40–60% of SCLC patients develop brain metastases (BMs) , , and less than 15% survive beyond two years , . In lung cancer management, contemporary advances in systemic therapies and focal radiation techniques have also tended to improve outcomes more in non-small cell lung cancer (NSCLC) than SCLC over the last decade . For patients with brain metastases, whereas upfront SRS Financials has become the preferred treated for limited brain metastases arising from most solid tumor histologies , whole brain radiotherapy (WBRT) remains the standard of care for SCLC . Although WBRT has demonstrated efficacy in controlling both local and distant intracranial disease there is now increasing concern about its acute and late toxicities particularly with respect to cognitive function and quality of life .

Stereotactic ablative radiation techniques such as radiosurgery (SRS) and fractionated stereotactic treatment (FSRT) are standard options for metastatic NSCLC and other solid tumor histologies with multiple randomized trials demonstrating similar overall survival and improvement in cognitive outcomes and quality of life (QoL) compared to WBRT . However, SCLC patients were excluded from these landmark trials due to multiple factors including concerns for short interval, multi-lesion central nervous system (CNS) progression specific to patients with SCLC histology, as well as the prevalent policy of prophylactic cranial irradiation (PCI) which has limited both the ability to study SRS without prior brain radiation and to randomize patients to arms that included WBRT , . Due to the paucity of data on SRS, WBRT has endured as the preferred treatment strategy for SCLC patients with one or more brain metastasis.

Today almost half of the world’s population is online and growing exponentially by 8% per year . Among these, over 2.8 billion people use social media. With nearly 79% of Twitter users outside the US , this modality offers a unique platform for global engagement. We have previously shown how this tool may be used to enable rapid dissemination of specialty-specific knowledge . To inspect the neglected condition of SCLC with BMs we used the global lens of the Radiation Oncology Journal Club (#RadOnc #JC) to critically review a large international cohort who received upfront SRS as an emerging option for patients (FIRE-SCLC).

This #RadOnc #JC occurred on Twitter™ from Saturday, June 21st 8AM to Sunday, June 22nd 4PM Central Standard Time (CST) in accordance with our usual protocol. The online journal club included limited-time open-access of the publication and an asynchronous online discussion followed by a live-hour to reduce barriers to participation, targeted online invitations to encourage diverse perspectives across disciplines and regions, moderation by a resident (IP) and diverse faculty (MK, RS, HS), and attendance by the study’s lead author (CR). Structured discussion topics (T1, T2, T3…) included an introduction for more general audiences then critical appraisal of the cohort study for application locally and globally by patients and providers. Natural evolution of these topics was allowed to draw out new lines of inquiry. Throughout, tweets were summarized using the social media content organization platform Wakelet for easier access to the knowledge-base generated by the discussion. Following the journal club, tweets were further reviewed, systematically organized into themes, and checked against existing literature to form the basis of the collated findings presented in this paper.

Over 80 individuals from 10 countries participated in the journal club with up to 120 participants responding to the anonymous polls (Table 1). These included radiation oncologists, medical oncologists, family physicians, residents, and a patient advocate. There was a total of 496 tweets, 205 retweets, 128 tweets with links and over 2.9 million impressions (Table 1). The Altmetric Attention Score, one composite measure of scholarly impact and online engagement with research output, was 227 (top 5%) as of July 24, 2020 . Thematic analysis resulted in four themes: limitations of the study, the changing role of PCI, emerging alternatives and adjunct treatments, and the impact on patients including informed consent. A slim majority of participants had already offered SRS as first-line treatment for SCLC BMs (50.6%, n = 77). Radiation oncologists mainly prompted the clinical consideration of upfront SRS (72%, 15.6% medical oncologists, 3.1% patients; n = 32). Locally ablative treatments were usually done by the central nervous system (CNS) team (46.7%, 25.8% by anyone, 24.2% by an SRS/FSRT specialist; 3.3% or the lung cancer team; n = 120).

Participant demographics from the June 2020 #RadOnc #JC. Active participants were defined as those who contributed to the discussion (i.e. excluding retweets or introductions). Unique tweets were total tweets minus retweets. Demographics only includes active participants.

Our global journal club discussion suggests that occasional use of upfront SRS (delivered as a single fraction or fractionated locally ablative therapy) for carefully selected cases of SCLC BMs in combination with MRI active surveillance is not uncommon among the #RadOnc community; however, patterns of care analyses suggest that upfront WBRT is used in the vast majority of SCLC cases , . Although consideration of upfront SRS is likely to be prompted more often by radiation oncologists, medical oncologists and patients are becoming increasingly aware of this potential option. The majority of participating radiation oncologists’ respondents indicated that their centers have a dedicated CNS team to perform SRS, which was followed by individual SRS specialists. In a minority of places, lung teams are involved in SRS. Earlier SRS studies for BMs were limited to treating 3 to 4 intracranial lesions. However, technological advancement, increasing expertise, and encouraging results have paved the way for trials evaluating treatment for a larger number of intracranial lesions . Additionally, the increased training in SRS and desire to decrease toxicity is helping to drive increased study and early adoption of SRS in this setting .

The First-Line Radiosurgery for Small Cell Lung Cancer (FIRE-SCLC) study is the largest analyses for upfront SRS (without prior PCI or WBRT) for SCLC BMs (n = 710). Compared to a WBRT cohort (n = 219) it concluded a similar median overall survival (mOS, 6.5 for upfront SRS vs 5.2 months for WBRT; p = .003) against a trade-off of shorter time to central nervous system progression (TTCP, 9.0 months vs not reached for WBRT; hazard ratio 0.38; p < .001). The trade-offs observed with SRS without WBRT in this study, including inferior CNS disease control without a decline in OS, appear similar to other histologies where upfront SRS is already well established by multiple randomized trials .

However, our journal club highlighted some of the significant barriers to recommending upfront SRS as a standard option at this time. Despite a trend in literature, regulatory bodies, and some practices to accept lower-level evidence as practice-changing, there are key limitations of non-randomized data. Although propensity score analyses can help mitigate confounding variables, they are not a substitute for randomization and cannot guarantee balanced confounders or statements of causality . In light of the clinical reality that SCLC patients treated with SRS would often be highly selected, even after propensity score matching it is likely that that biases from uncontrolled and unmeasured confounding would remain. Moreover, the rate of post-treatment MRIs differed betwee