Is it acceptable to treat newly diagnosed small cell lung cancer with limited brain metastasis with upfront SRS?

First, to be clear, there's not good evidence regarding the role of radiosurgery in small cell patients who have not had WBRT or PCI. In patients without brain metastases, there's a clearly defined and clinically significant survival benefit, which seems to result from both control of existing metastases and prevention of new lesions. In my opinion, this suggests that in patients who already have brain metastases a similar benefit probably exists, because we would assume that their risk of further metastases is higher than in those who have no mets to start with. The wrinkle in the PCI story is a Japanese randomized trial presented at ASCO this past year, suggesting that if you image the patients, then PCI might be withheld without a detrim...

This excellent question was posed in 2014 and it may be worth re-visiting today in 2020, as interest in the potential role of first-line SRS (without prior WBRT or PCI) has increased for carefully selected patients with small cell lung cancer (SCLC) brain metastases.

One important development in the last year is that the NCCN Small Cell Lung Cancer guidelines, which view WBRT as the standard-of-care for SCLC brain metastases, were updated to acknowledge first-line SRS as an acceptable treatment strategy for carefully selected patients (and full disclosure: I am one of several radiation oncologists on this NCCN panel). In version 1.2021 of the guidelines, the ‘principles of radiation therapy’ section state that, “brain metastases should typic...

This is an excellent, and very clinically relevant question, for which I am going to offer a contrarian viewpoint. First of all, as with all patients, we have to define the intent of therapy. If they have small cell lung cancer (SCLC) with a brain metastasis or metastases, all treatments henceforth should be done with palliative intent aimed at OPTIMIZING quality of life. If they have limited stage SCLC without brain metastases, all treatments henceforth should be done with curative intent.

In limited stage SCLC, we have to keep in mind that the trials of PCI were done in the era before MRI brain and patients had poor quality CT brain. Therefore, they were likely treating people with brain metastases, but they were deemed to not have brain m...

Patients presenting with a solitary, or "limited", visible brain metastasis have extensive disease regardless of performance status or identifiable disease elsewhere. Standard practice is whole brain. The dose and fraction scheme are arguable. The need to start systemic therapy is obvious but usually not an emergency, and that is stemmed by the brain issue. Survival at 2 years is <10%.

Substituting stereotactic treatment as suggested, and addressed by Decker, may have been done, but is not evidence based, and since small infrequently is solitary, and risk is to the entire brain, has little appeal to me. Also, it is expensive and takes days to plan. Many years ago in Canada and still in Europe, and very commonly in the Slotman ED-PCI study, 4...

At our institution, we have historically used WBRT to manage patients with SCLC and brain metastases (even if only a single brain metastasis was present on MRI) if they have never received PCI. This practice pattern was largely derived from the exclusion of patients with SCLC from all RCTs testing local brain-directed therapy +/- WBRT and older data supporting the use of PCI in patients with both LS and ES-SCLC. However, the Japanese PCI study for ES-SCLC has questioned the appropriateness of radiotherapeutic treatment of the uninvolved brain, especially in the context of routine surveillance brain MRIs.

Consequently, we designed a single-arm, phase II clinical trial in which patients with SCLC and 1-10 brain metastases who are naive to prio...

It is odd that for both limited and extensive stage we do PCI and for visible cancer in the brain we talk about SRS alone first to expedite chemotherapy. For palliative stage IV disease, delaying chemo by few weeks would not affect survival. If a patient has impending chest symptoms outside the brain for which they need to start chemo soon, that can often be taken care by palliative RT to that site along with brain at same time.

There is decent data suggesting the response rate in the brain with chemotherapy is the same as it is in the thorax and I feel completely comfortable treating asymptomatic brain metastases with chemotherapy as long as more frequent imaging of the brain is employed. As for symptomatic patients, I believe WBRT is the right approach. Treatment can be kept short to prevent delays in chemo for pts with symptomatic disease elsewhere

SRS may not be appropriate due to the amount of edema, as well as the concern that local control may be worse (Emory or UAB series and my anecdotal experience) due to the infiltrative nature of small cell brain metastases as compared to metastases from other histologies (Baumert et al., PMID 16814946.)

I've spoken with Rodney Wegner who has published observational series using gamma knife and cyberknife in SCLC, and he tells me that he *is not* an advocate of initial SRS in SCLC. He said: "Is someone misquoting my paper again?" Even in an expedient situation, some urgency to start systemic therapy, let's say due to SVC, a solitary met, with or without symptoms, can be treated with steroids and chemotherapy if WBRT with 20 Gy/5fx or 30 Gy/10 fx is deemed to be too long to wait. No matter number of brain mets, or sites of other systemic disease, even a solitary brain met constitutes Stage IV or Extensive disease.

Regarding updates in 2023, as a follow up to FIRE-SCLC (Rusthoven et al., PMID 32496550), our group recently published the CROSS-FIRE study in JNCI (Rusthoven et al., PMID 37142267), which compared first-line SRS outcomes in SCLC to those in NSCLC.

The international study analyzed two cohorts, including a retrospective dataset (892 SCLC and 4,785 NSCLC patients) and a prospective dataset (98 SCLC and 814 NSCLC patients) from the JLGK0901 trial (Yamamoto et al., PMID 24621620).

Brief summary of results:

• After SRS, OS was superior for NSCLC over SCLC patients (retrospective cohort: median 10.5 vs 8.6 months, p<.001).
• CNS control was superior for NSCLC over SCLC overall, but no significant differences were observed in propensity score-matched...

"Limited" brain metastases from small cell may be an oxymoron. There is very limited data on SRS in the upfront setting. There are a few publications on up front SRS for small cell. At the end is my text from one of my texts on the matter.

This is not to say that I have not done SRS upfront for limited intracranial volume. If a patient has only a single SCLC brain metastasis, is elderly, and has poor cognitive function, WBRT will be very poorly tolerated with significant cognitive worsening likely in the short term, then I would consider it. Imaging for intracranial disease is often much fuzzier for small cell so I've generally been a little more generous and less conformal with my target delineation. Though my threshold to recommend WBRT th...

For us, the standard practice for significant mets is SRS upfront followed by chemo and then WBRT outback. Since our time to SRS is less than 48 hrs, this keeps therapy on track.

In this series, 14 patients had GK upfront. http://www.redjournal.org/article/S0360-3016(12)01725-7/abstract. The results for the upfront srs mirror our own for a similarly small number of patients. There is also a series from Pittsburgh -Wegner et all published in The Red Journal in 2012.