Thread by @christine_lovly

Major update for small cell #lung cancer! #LCSM

With @juliensage + @FoundationATCG, our paper now on @bioRxiv:

►Genomic analysis of *3,600* pts with SCLC; largest SCLC study to date!

►Multiple interesting findings discussed in this 🧵
biorxiv.org/content/10.110…

🧵2
This study is unique in many ways:

> The #SCLC cohort studied came mostly from community sites --> representing a more typical “real-world” cohort of SCLC.
> The genomic data are tied to clinical data + outcomes.

#LCSM

🧵3
To the best of our knowledge, our study analyzes the largest number of SCLC tumors from African ancestry to date:
> n=256 AFR cases
> 7.1% of the entire cohort
#Diversity in clinical studies is critical!!
See tweet 🧵9 for more details.

🧵4
Given the large sample size, we were able to study SCLC genomics by metastatic site.
>747 liver mets
>116 brain mets
>901 lymph node
>+ more (see Table 1)

🧵5
Further, our study contains the largest cohort studied of putative “transformed SCLC” (t-SCLC)
> n=121
> including 107 EGFR-mutant #SCLC cases
@EGFRresistors, #LCSM

🧵6
What did we learn?

Our analysis of these “real-world” data from an SCLC cohort of unprecedented size led to numerous new findings that may have been previously missed due to limited sample size of prior studies

➡️Some take home messages from the study in the continued 🧵

🧵7

We define a cohort of TP53/RB1 wild-type SCLC tumors

➡️~5% of all SCLC
➡️TP53/RB1 WT tumors have a low TMB
➡️More frequently found in African American patients

#LCSM small cell #lungcancer

🧵8

We identify SCLC tumors containing #HPV DNA

➡️HPV+ tumors are enriched within the cohort of TP53/RB1 WT SCLC
➡️indication that some cases of SCLC may have a viral origin!
➡️This subset of patients may respond to specific immunotherapies, including vaccination?

🧵9

We identify recurrent #STK11 mutations in SCLC, which are enriched in patients of AFR ancestry.

➡️Pts with STK11 mutations have poorer overall survival compared with the STK11 WT cohort.
➡️Possible implications for immunotherapy treatment?

🧵10

We present the 1st analysis of #SCLC #genomics broken down by anatomical location, with a particular focus on #brain #metastases.

SCLC brain metastases:
➡️have higher TMB
➡️are enriched for PTEN mutations compared to primary tumors or liver metastases.

🧵11

We analyze a large cohort (n=121) of putative tSCLC w/ driver mut typically found in NSCLC

➡️EGFR (ex19del > L858R in SCLC cases!)
➡️ALK
➡️ROS1
➡️RET
➡️NTRK

Need for rebiopsy of all driver+ NSCLC to look for SCLC
@EGFRResisters @ALKLungCancer @ros1cancer @RetRenegades

🧵12

Plus many more interesting findings in the paper!

➡️Please check it out and share / retweet! ⬅️

🌟We welcome discussion + feedback🌟

#LCSM, @IASLC , @Oncoalert, @SageJulien @FoundationATCG

biorxiv.org/content/10.110…

🧵13
OVERALL:
➡️While the field has been focusing on SCLC transcriptional subtypes, these data underscore the existence of genetic subtypes too.
➡️We hope this paper is a resource for scientists exploring various aspects of SCLC biology. #LCSM

🧵14
🌟Key findings🌟
> 3600 SCLC cases
> Genomic, ancestry, clinical data
> New genetic subtypes
> TP53/RB1 WT SCLC
> HPV + SCLC
> STK11 mut SCLC, enriched in AFR ancestry
> Brain mets: higher TMB, more PI3K pathway mutations
> EGFR, ALK, ROS1, RET, NTRK SCLCs
@OncoAlert #LCSM

🧵15 + final
🌟Most importantly🌟

In the eve of #WorldLungCancerDay, we sincerely hope that these data will help to improve care for all patients with SCLC worldwide!

@IASLC @OncoAlert @LUNGevity @lcfamerica @GO2Foundation @lcrf_org @Stanford @VUMC_Cancer