Would you consider SBRT for an inoperable T1-T2 N0 SCLC?
How do you manage inoperable T1-T2N0 SCLC?
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The concept of using SBRT in the setting of inoperable early-stage node negative small cell lung cancer (SCLC) is interesting and replicates the concept of SBRT as a surgical surrogate. In other words, SBRT is used to manage the primary lesion, as with early-stage non-small cell lung cancer (NSCLC). Unlike NSCLC however, surgically resected SCLC is then followed by adjuvant chemotherapy and often prophylactic cranial irradiation (PCI) because of historic patterns of failure for SCLC which suggested it had a higher propensity for distant failure. There have also been a few old trials which suggested the benefit of adjuvant chemotherapy. At Cleveland Clinic, we have been following this model for SBRT then adjuvant chemotherapy then PCI for inoperable early-stage SCLC for some years now and published our early experience in Videtic et al., PMID 24674402. One of the main reasons for publishing this experience was less to do with the SBRT component and more to do with reporting on the ability to deliver adjuvant chemotherapy in what is a vulnerable population. At ASTRO 2015, there was an oral presentation from Japan describing over 60 such patients treated with this approach whose data was collected from a consortium of Japanese centers. Essentially they reported what we have noted, ie, efficacy, excellent local control, and expected patterns of failure.
The standard is surgical resection. As some are medically impaired, TRT options include SBRT, I know of no data or series. My practice has been 45 Gy/3wks. Also not evidence-based. Some of these nodules may sample just SCLC, but harbor carcinoid or NSCLC.
In resected, 4 Cycles Plat/Etop.
Low incidence of brain mets. I’m not recommending PCI for those over 70, or surgically treated Stage 1. It may be worth a discussion.
As @Dr. First Last says, the concept of using SBRT as a surgical surrogate for early-stage SCLC is rational. We have not routinely done this at our center and for now, I'd still consider the standard of care (for inoperable patients) to be concurrent chemoradiation to 45Gy BID. Other data is likely to be published soon, including the Japanese series mentioned. One question that will remain to be answered is whether full SBRT doses (i.e. BED>100) will be necessary given that SCLC is usually more radioresponsive, but in a situation where one has already committed to using SBRT and there are no particular concerns about normal tissue constraints, it probably makes sense to stick to standard SBRT dosing.
Regarding adjuvant therapy, I think that adjuvant chemo remains indicated, since the risk for distant metastasis is so high in this disease, and there isn't yet great evidence that this risk is absent just because the primary disease is low-volume. PCI likewise is the standard of care. However, we presented retrospective data at ASTRO a couple of years back indicating that the risk of brain metastasis is lower in Stage I/II patients compared to Stage III patients, which suggests that the benefit of PCI likewise may be lower for Stage I/II patients. This data is as-yet unpublished, so for now I would certainly consider adjuvant chemo and PCI to be the standard of care for early-stage SCLC however you treat the primary lesion (surgery, SBRT, conventional RT).
I have used both SBRT followed by platinum/etoposide, SBRT alone, and the hyperfractionated 4500 cGy with 150 cGy BID regimen with concurrent platinum/etoposide. This is not common for an SCLC presentation and patient preference and co-morbidities need to be considered in determining the appropriate treatment plan. I have typically not used PCI.
Clearly, the reason they are not a surgical candidate matters and it remains the standard for T1-T2 N0 SCLC. Surgery is both diagnostic and therapeutic and also remains the standard local control option when feasible. Early-stage small cell T1-T2 N0 can be an incorrect diagnosis and this is not captured in cancer registries well. When resected, pathology can be modified to carcinoid, atypical carcinoid, or large cell neuroendocrine carcinoma that can result in modified management.
There are studies that have reported the results with SBRT. Besides the experience that Dr. @Dr. First Last mentioned above, there are small series reporting outcomes, but they are limited and are partially listed in the references for the NCCN guidelines. Common amongst all of the studies are:
-1- An approximate 50% distant mets pattern of failure;
-2- Patients who received chemotherapy did better
-3- There were long term survivors (> 2-3 years) that are similar to SBRT for early stage NSCLC
-4- All retrospective multi-institutional studies
References:
Shioyama, Y et al., PMID 29983096.
Verma V et al., PMID 28011047.
Singh R, et al., PMID 31232723.
There has been one comparison to conventionally fractionated treatment for Stage IA SCLC and all received chemotherapy that suggested no difference in clinical outcomes using NCDB data. Of note, for conventional radiation, no note is made whether the treatment was solely once daily or included BID.
For those seeking additional references to support SBRT (SABR) for stage I SCLC, a nice editorial/review by Drs. Verma, @Dr. First Last, and @Dr. First Last can be found at the Oncologist PMID 26764248, ahead of several additional publications by the same authors (PMID 28011047, PMID 28408183, PMID 30773182), which, in summation, demonstrate 3y local control >95%, recommendation for chemotherapy (also known from previously mentioned surgical series), indeterminate benefit for PCI (a topic unto itself, with ongoing trials evaluating its role in more advanced limited-stage presentation setting), and no difference in OS when compared with conventionally fractionated concurrent chemoradiotherapy. Another series employing moderate hypofractionation (4-8 fractions, with only 8 patients receiving chemotherapy) was published by the Japanese JRS-SBRTSG (Shioyama et al., PMID 29983096).
No N-0 in Intergroup trial. One might pose this to CONVERT and recent Scandinavian trialists. Overview of surgically treated N-0 showed a low incidence of CNS failure.
The EQD and BEDs go up from 45 BID to 60 BID to 70 Gy to 50/5 SBRT. CALGB says 70 is as good as 45 BID at nearly 5 years.
For elderly, comorbid patients, and T1N0 patients, it seems like SBRT + chemo is reasonable. Is EBUS mandatory first or is a reasonable PET result sufficient (groans from the crowd...)?