Jeff Ryckman Profile picture
Jul 26, 2022 β€’ 28 tweets β€’ 26 min read β€’ Read on X
Is there a role for Local Tx of the Primary Tumor for Patients with Metastatic Cancer?

🚫Many studies demonstrate no benefit.
πŸ“ŒWe performed a MetaAnalysis to evaluate the average effect of Local Tx across various tumors.

A thread🧡#AMSM #PRIMETX
redjournal.org/article/S0360-…

1/25
Critics of Local Tx to the Primary Tumor

πŸ“Œ Many providers think local control of the primary tumor in the setting of M1 dz is akin to β€œclosing the barn door after the horse has bolted”
πŸ“Œ Ian Tannock wrote a fantastic article on this back in 2000.

pubmed.ncbi.nlm.nih.gov/11759650/

2/
Supporters of Local Tx

πŸ“ŒSome support aggressive ablation of all sites due to the enhanced ability to detect occult disease with improved imaging technologies and πŸ“‰ toxicities with complete ablation.

pubmed.ncbi.nlm.nih.gov/35831494/
pubmed.ncbi.nlm.nih.gov/31182289/
pubmed.ncbi.nlm.nih.gov/34742582/

3/
To date,

πŸ“ŒSome trials have demonstrated an OS benefit with Local Tx, while many others have shown no benefit.
πŸ“ŒAs a recent meta-analysis investigated the utility of ablation of metastasis, the focus of thiswork is Local Tx to the primary tumor.

pubmed.ncbi.nlm.nih.gov/33237270/

4/
Methods

πŸ“Œ Comprehensive search on PubMed/MEDLINE and Cochrane Review.
πŸ“Œ Primary outcome measures of OS and PFS.
πŸ“Œ RCTs that included simultaneous local consolidative Tx to the primary tumor and metastases (e.g., Gomez for NSCLC) were excluded.
bit.ly/PRIME-TX_Liter…

5/
Results

πŸ“Œ Literature search revealed 11 studies from 2001-2021, comprising 4,952 patients who underwent systemic therapy +/- local treatment to the primary tumor.
πŸ“Œ Bookmark these Tables and view the different sheets to follow these tweets.

bit.ly/PRIME-TX_Tables

6/
Results: Efficacy

πŸ“Œ OS and PFS were not significantly improved with Tx of the primary tumor.
πŸ“Œ There was a significant difference in summary effect size on PFS between trials that used surgery and the trials that used RT as the primary local Tx modality.

7/
Results: Palliative treatment to the primary tumor in the no local treatment (control) arms

πŸ“Œ Rates of palliative treatment to the primary tumor for symptoms or progression in the no local treatment (control) arms ranged from 6-18% (Table 2, post 6)

8/
Results: Physician-Graded Toxicity and QoL

πŸ“Œ Only 4 studies reported QoL (3 of which were for breast cancer; Table 3, post 6)
πŸ“ŒMore robust QoL data is needed, with particular attention to later stages where symptomatic progression and palliative needs are often more common

9/
Results: The Upfront Surgery trials (n=6/7)

πŸ“Œ Typically large, locally advanced tumors.
πŸ“Œ MTT initiation of systemic therapy ranged from 19 to 34d after surgery.
πŸ“Œ Twice as many patients (4.4β†’ 8.9%) failed to initiate systemic therapy in the local therapy arms.

10/
Discussion: RT trials

πŸ“Œ The two primary tumor types driving the OS benefit in the low M1 population treated with RT include prostate ca (n=2 trials; #STAMPEDEArmH, #HORRAD) and NPC (n=1 trial; SYSUCC5010).
πŸ“Œ Surgery trials investigated very different populations!

11/
Discussion: Surgery trials

πŸ“Œ Most surgical studies were dominated by large locally advanced or initially unresectable tumors. What about smaller, more easily resectable tumors?
πŸ“Œ Most surgical studies investigated upfront surgery (n=6/7). What about deferred surgery?

12/
Discussion: #stcsm

πŸ“Œ #REGATTA: Gastric cancer. Upfront Surgery. S-1/Cisplatin until progression or toxicity.
πŸ“Œ Trend to πŸ“‰PFS/OS.
πŸ“Œ Tumors involving upper 1/3 of stomach may have πŸ“ˆ compliance issues with chemo.
πŸ“Œ Deferred surgery πŸ”œ#RENAISSANCE?
pubmed.ncbi.nlm.nih.gov/26822397/

13/
Discussion: #CRCSM

πŸ“Œ#JCOG1007: 1-3 unresectable mets. Upfront surgery. FOLFOX6 or CapeOX-Bev.
πŸ“ŒTrend to πŸ“‰ PFS/OS.
πŸ“Œ60d mortality 11% on #CAIRO4.
πŸ“ŒShould regular endoscopic surveillance guide potential role of deferred primary tumor surgery?

pubmed.ncbi.nlm.nih.gov/33560877/

14/
Discussion: #kcsm 1/2

πŸ“Œ Upfront surgery. 1) SWOG: πŸ“ˆ OS (outdated IFN era). 2) #CARMENA: 🚫 OS benefit (TKI era)
πŸ“Œ Deferred nephrectomy may be preferred to select for patients who respond to systemic Tx (#SURTIME)
πŸ“Œ Reserve for 1 IMDC risk factor?
lists.papersapp.com/Lt7VWzrOoPuN15…

15/
Discussion: #kcsm 2/2

Cytoreductive Nephrectomy (CN) in 2022: Where are we now?
πŸ“Œ CN: Still Necessary, Obsolete, or Obselete but Necessary?
πŸ“Œ 2022 ASCO and EAU Guidelines support CN in select patients.
sciencedirect.com/science/articl…
sciencedirect.com/science/articl…
sciencedirect.com/science/articl…
16/
Discussion: #BCSM 1/2

πŸ“Œ Upfront surgery: #ABSCG28, #MF0701.
πŸ“Œ Deferred surgery: #TataMemorial, #E2108.
πŸ“Œ Only one trial (MF07-01, positive margins in 0%) suggests πŸ“ˆ OS with local therapy in an enriched population of HR+ solitary bone metastases.

lists.papersapp.com/Lt7VWzrOoPuN

17/
Discussion: #BCSM 2/2

πŸ“Œ Overall PFS is not reported in all 4 breast studies. There appears to be a distant PFS detriment with surgery (Cochrane review PMID 29542106; Tata memorial), further supported by ABSCG-28.
πŸ“Œ Fantastic review here: pubmed.ncbi.nlm.nih.gov/35578060/

18/
Discussion: #PCSM

πŸ“Œ There is an OS benefit with prostate RT for < 5 bone mets (#HORRAD) or per #CHAARTED definition (#STAMPEDEArmH).
πŸ“Œ Q: Does prostate RT provide benefit the setting of docetaxel Β± abi? A: Awaiting the #PEACE1 RT publication.
πŸ“Œ Role for prostatectomy?

19/
Discussion: #NPXSM

πŸ“Œ For some tumor locations (e.g., NPX), an uncontrolled primary tumor may cause substantial morbidity and even mortality. Therefore, the attainment of local control could easily impact survival.
πŸ“Œ Fantastic prognostic model here: pubmed.ncbi.nlm.nih.gov/32853711/

20/
Discussion: #SCLC

πŸ“Œ#CREST (pre-IO era) delivered lower doses of thoracic consolidation (30Gy/10Fx).
πŸ“Œ OS benefit most pronounced when only patients with residual thoracic dz were included.
πŸ“Œ Is the role for thoracic RT for ES-SCLC in the IO-era? pubmed.ncbi.nlm.nih.gov/31673520/

21/
Discussion: #NSCLC

πŸ“Œ No trials of which we are aware randomized to local Tx to primary tumor alone (e.g., Gomez also treated metastases).
πŸ“Œ PRIME-LUNG is investigating upfront SABR to the primary tumor.
πŸ“Œ PI @ShankarSiva from @PeterMacCC

clinicaltrials.gov/ct2/show/NCT05…

22/
I want to use this moment to highlight the utility of a BCC for such a large co-author group as this to avoid email fatigue.

HT @NicholasZaorsky for his fantastic mentorship πŸ™



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Conclusion

πŸ“Œ No consistent PFS/OS benefit in the overall population.
πŸ“Œ PFS differed significantly between trials utilizing surgery vs. trials utilizing RT.
πŸ“Œ More data needed to determine differences in subgroups (e.g., type/sequencing of Tx w/i each primary tumor type).

24/
Special thanks to all co-authors for their support!πŸ™

Please, be mindful: Site-specific discussions for each primary tumor type in this Tweetorial are the tip of the iceburg (read: hopelessly oversimplifed). When in doubt, discuss at tumor board.

Thanks for stopping by!

25/25
Here is the working link for the cited papers: lists.papersapp.com/Lt7VWzrOoPuN
What might explain πŸ“‰distant PFS with breast surgery as suggested by Tata Memorial and ABSCG-28?

Here is my stab at it (HT @_ShankarSiva). Surgery may be immunosuppressive? But this hypothesis doesn't explain the clear benefit of surgery in #MF0701 & RCC
@Docace911 - any thoughts on the curves separating after 3y on MF07-01? Also, any thoughts on the theory as to why distant PFS might be worse w breast surgery?

Huge fan of your work! Obviously, this is a different Q than MDT. Please DM if you feel these are controversial topics.

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