Thread by @subatomicdoc

Can we improve how we treat cancer with stereotactic radiation? Yes, we can.

Here’s a @ClinOncology editorial with Drs. @MichaelTMilano & Alina Mihai on including clinical treatment volumes (CTVs) for microscopic disease.
authors.elsevier.com/a/1eVwJ3K%7E8R…
#radonc #medphys 1/

Radiation therapy (RT) can non-invasively treat microscopic disease. In curative settings, RT complements or competes w/ surgery to improve cancer care and patient outcomes.

I’ll discuss how matters using curative lung cancer and metastatic disease as examples. 2/

Stereotactic RT lets us give very high doses safely. Advances in medical physics & computer programming, matched w/ clinical trials, show we can improve tumor control & decrease central “in-field” failures. Its evolution initially required ignoring microscopic disease. 3/

The hope is that penumbra dose (the fall off surrounding the visible tumor) sufficiently eradicates cancer cells that we don’t see. There is some evidence suggesting otherwise, and that we need to re-evaluate what we know to design stereotactic RT fields. 4/

Let’s start by discussing lung cancer. We have evidence suggesting stereotactic RT is better than conventional at reducing local failures in early stage lung cancer. Here is the CHISEL trial as an example. #lcsm #radonc thelancet.com/journals/lanon… 5/

We know that microscopic disease is a problem in lung cancer, requiring expanded margins for chemoradiation.
Here is some surgical data backing up its use.

But what about in early lung cancer? redjournal.org/article/S0360-… 6/

We know from longer term follow up of RTOG 0236 that after stereotactic RT, there can be higher lobar failure rates away from the primary tumor, in additional to nodal failures. jamanetwork.com/journals/jamao… 7/ #lcsm

Some argue most stereotactic RT failures are distant. What if distant failure is linked to RT dose distribution? Some data suggest dose of <20.8Gy to the 3 cm around the PTV may matter thegreenjournal.com/article/S0167-… 8/

Follow up data compared stereotactic RT with VMAT/conformal to Cyberknife. The latter had higher mean doses and lower local and distant failure, especially in the area around the PTV. thegreenjournal.com/article/S0167-…
9/

Why would the equipment matter? One possibility: coplanar VMAT is more likely to miss disease above/below and under-dose both visible tumor if it moves too much, or because there is microscopic disease under-dosed. 10/

Another regarding microscopic disease in lung stereotactic RT from : incidental dose >20 Gy to hilar nodes had lower observed relapse rates. Interestingly, similar dose threshold to studies above. linkinghub.elsevier.com/retrieve/pii/S…
11/

Understanding tumor biology is essential. Surgeons know STAS (spread through air spaces) is a negative prognostic factor.

Radiation oncologists don’t have anything much on it - yet.
#lcsm
jto.org/article/S1556-…
12/

STAS may be particularly relevant in lower grade adenocarcinomas on consider whether a smaller, non-lobectomy resection carries a higher risk of recurrence.

Pertinent to #radonc?
jto.org/article/S1556-… 13/

So...how do we ensure we don’t miss?

We need to start understanding STAS, collaborate with surgeons and pathologists in prospective surgical cohorts using whole mount pathology #lcsm #tssmn #pathologists mdpi.com/1718-7729/15/5… 14/

We can correlate PET-CT, correlate radiomics to pathologic findings of STAS (or other features) to better define CTVs. We also need more studies confirming the findings above suggesting 20-21 Gy may be an effective dose for microscopic disease with stereotactic lung RT. 15/

We can consider use of stereotactic ‘dose painting’ to make the penumbra dose designed to be less steep where it may help treat microscopic disease.

Even now, should coplanar VMAT have better superior-inferior margins to avoid marginal misses? 16/ #medphys

I’ve outlined potential value for CTVs in stereotactic RT for the curative treatment of lung cancer. Next, let’s think about implications of designing RT to treat microscopic disease in the metastatic setting. 17/

Radiation oncologists increasingly discuss how stereotactic RT can improve cancer outcomes in the metastatic setting. But we’re inserting use of the technology into a clinical setting in which we’re not as familiar with patterns of failure. 18/

Radiation oncologists toy with the word ‘cure’ in oligometastatic disease. If you do, you need to understand the patterns of failure, by histology and metastatic site, and how microscopic disease may differ. 19/

For brain metastases, autopsy series show varying degrees of microscopic infiltration by different primary tumor histologies. Two examples:
redjournal.org/article/S0360-…
oncotarget.com/article/4201/t… 20/

For liver metastases, microscopic tumor may extend beyond MRI-defined disease and be potentially under-dosed with stereotactic RT treating only what we see. redjournal.org/article/S0360-… /21

Stereotactic RT for spinal metastasis has already recognized the need for a CTV. We need to methodically do this process for other metastatic sites.
redjournal.org/article/S0360-…
redjournal.org/article/S0360-… /22

Defining CTVs for metastases is a great research opportunity to collaborate with medical oncology, pathology, radiology, and surgery. Clinicopathologic and patterns of failure studies are essential to determining when stereotactic RT adds value worth the potential toxicity. 23/

It’s time we re-include CTVs in treatment planning for stereotactic RT, to account for the biologic realities we initially chose to ignore during stereotactic RT’s early development. Patients deserve the best radiation oncology can offer: well-designed treatment. 24/

So what do you think? What do we need to do next?
FYI @sueyom @radiopeppe @ggmspeijer @Psbasran @seanmmcbride @fumikochino @rweichselbaum

Thanks again to Drs. Milano and Mihai for the help in publishing this idea 🙂🙏

Yay! Found out @alinamihai2000 is on Twitter! Thank you Dr. Mihai!

FYI @biniamkidaneMD @TomVargheseJr @ElliotServaisMD @seancwightman @ssihag_MSK @DanRaymondMD