Thread by @jryckman3

Is there a role for Local Tx of the Primary Tumor for Patients with Metastatic Cancer?

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

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

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Critics of Local Tx to the Primary Tumor

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

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

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Supporters of Local Tx

📌Some support aggressive ablation of all sites due to the enhanced ability to detect occult disease with improved imaging technologies and 📉 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,

📌Some trials have demonstrated an OS benefit with Local Tx, while many others have shown no benefit.
📌As 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/

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Methods

📌 Comprehensive search on PubMed/MEDLINE and Cochrane Review.
📌 Primary outcome measures of OS and PFS.
📌 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

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

bit.ly/PRIME-TX_Tables

6/

Results: Efficacy

📌 OS and PFS were not significantly improved with Tx of the primary tumor.
📌 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

📌 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

📌 Only 4 studies reported QoL (3 of which were for breast cancer; Table 3, post 6)
📌More 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)

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

10/

Discussion: RT trials

📌 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).
📌 Surgery trials investigated very different populations!

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Discussion: Surgery trials

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

12/

Discussion: #stcsm

📌 #REGATTA: Gastric cancer. Upfront Surgery. S-1/Cisplatin until progression or toxicity.
📌 Trend to 📉PFS/OS.
📌 Tumors involving upper 1/3 of stomach may have 📈 compliance issues with chemo.
📌 Deferred surgery 🔜#RENAISSANCE?
pubmed.ncbi.nlm.nih.gov/26822397/

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Discussion: #CRCSM

📌#JCOG1007: 1-3 unresectable mets. Upfront surgery. FOLFOX6 or CapeOX-Bev.
📌Trend to 📉 PFS/OS.
📌60d mortality 11% on #CAIRO4.
📌Should regular endoscopic surveillance guide potential role of deferred primary tumor surgery?

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

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Discussion: #kcsm 1/2

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

15/

Discussion: #kcsm 2/2

Cytoreductive Nephrectomy (CN) in 2022: Where are we now?
📌 CN: Still Necessary, Obsolete, or Obselete but Necessary?
📌 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

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

lists.papersapp.com/Lt7VWzrOoPuN

17/

Discussion: #BCSM 2/2

📌 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.
📌 Fantastic review here: pubmed.ncbi.nlm.nih.gov/35578060/

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Discussion: #PCSM

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

19/

Discussion: #NPXSM

📌 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.
📌 Fantastic prognostic model here: pubmed.ncbi.nlm.nih.gov/32853711/

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Discussion: #SCLC

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

21/

Discussion: #NSCLC

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

clinicaltrials.gov/ct2/show/NCT05…

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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 🙏



23/

Conclusion

📌 No consistent PFS/OS benefit in the overall population.
📌 PFS differed significantly between trials utilizing surgery vs. trials utilizing RT.
📌 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!🙏

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 📉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.