David Sher

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David Sher

David Sher

@DavidSherMD

"Ultimately, the secret of quality is love. You have to love your patient, you to have to love your profession, you have to love your G-d." Avedis Donabedian

Dallas, TX Katılım Nisan 2019
725 Takip Edilen1.7K Takipçiler
David Sher
David Sher@DavidSherMD·
@PaulJiL @ASCO Very interesting preliminary result. KN-412 was actually pretty close but likely needed a few tweaks… What was the biomarker selection? Could the adjuvant pembro have made the difference given the CPS-positive population? Looking forward to the results!
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Pablo Jiménez
Pablo Jiménez@PaulJiL·
#ASCO26 Eager to review the Ph2 #KEYCHAIN presentation about patients with unfavorable-risk p16+ HNSCC Thought-provoking trial in this difficult space to reach a H&N PACIFIC/ADRIATIC protocol as in lung. Unlike KN412, pembro is replacing cis, not added to CRT Radical RT+pembro vs RT+Cis 📈2yPFS: 84vs70%; HR 0.57 (0.25-1.31) p=0.09 🟢 📈2yOS: 98vs85%; HR 0.33 (0.09-1.28) p=0.048🟢 ⚠️lenient 1-side α=0.15 June 1. HallD1. 4:30. @drlorenmell #hncsm @OncoAlert @brunolarvol
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David Sher
David Sher@DavidSherMD·
It was clear that the IMPT plans were better than IMRT. I think they could have been substantially better, but regardless, the improved dosimetry did not translate into long-term PRO gains. At all. A critical question is understanding the determinants of PRO results in HNSCC patients. How much does expectation, mood, equilibrating to the new normal, genetics all play into these outcomes?
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Pierre Blanchard, MD
Pierre Blanchard, MD@PBlanchardMD·
No QoL difference with IMPT vs IMRT in oropharyngeal cancer in the TORPEdO 🇬🇧 trial. How to explain the differences w/ @SJFrankMD 🇺🇸 trial? Planning? Patients? Crossover in the 🇺🇸 trial? Real absence of difference? Cc @EmmaHall71 @
Pierre Blanchard, MD tweet mediaPierre Blanchard, MD tweet mediaPierre Blanchard, MD tweet mediaPierre Blanchard, MD tweet media
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David Sher
David Sher@DavidSherMD·
It is an exciting paradigm, and our current phase II RCT (INVERT) is approximately 75% accrued. We are extremely grateful to the patients and families who have enrolled in these studies! We are working on both an AI-free approach as well as automation of the entire workflow (i.e. auto-segmentation of the nodes and malignancy classification). More to come over the next year on these endeavors. We hope to finish accrual on INVERT over the next several months and, if successful, move this regimen to a multi-institutional randomized trial.
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David Sher
David Sher@DavidSherMD·
While ENI dose de-escalation is clearly better 50-56 Gy, it is not a substitute for INRT. In INRT-AIR, we contoured standard ENI volumes to assess the delivered dose. The median V40 to the ENI PTV was 50%, and the median V30 was 58%.
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David Sher
David Sher@DavidSherMD·
Absolutely terrific work by @DrSymYoung to report the long-term outcomes of our INRT experience from two prospective trials (INRT-AIR and DARTBOARD). Short version: with long-term follow-up (median 5.2 years for INRT-AIR, 3 years for DARTBOARD), we've seen zero solitary elective nodal recurrences. Longer version: ESTRO has highlighted novel approaches to managing the elective neck in HNSCC, and I believe the future will be very different than the present. Current ENI fields deliver the majority of the integral dose to patients and contribute substantially to critical structures (swallowing and xerostomia OARs). Minimizing ENI dose and volume may meaningfully improve the short- and especially long-term tolerance of radiotherapy. A few more thoughts on our INRT paradigm below:
OncoAlert@OncoAlert

Day FOUR of #ESTRO26 Coverage by OncoAlert 🚨 Omission of elective nodal irradiation in HNSCC: long-term results and patient-level pooled analysis from 2 prospective trials (INRT-AIR & DARTBOARD) Presenter Sympascho Young 🇺🇸 A patient-level pooled analysis of 117 patients from two prospective trials (INRT-AIR and DARTBOARD) showed that omission of elective nodal irradiation for HNSCC was oncologically safe long-term, with a 0% rate of solitary elective nodal recurrence at 5 years. The trials used an involved nodal radiotherapy (INRT) approach assisted by an artificial intelligence model for detection of suspicious nodes. @DrSymYoung @DavidSherMD #RadOnc @ESTRO_RT @yasemin09896924 @LindaMrissa @christian_roenn @Valeriadionisi @gerryhanna @clchiang_hk @mtugceyilmaz @B_Tomasik @gmpetrianni @CiroFranzese1 @Atem84 @piet_ost @brachyexpert @BlanceS90 @The_PT_Explorer @BarbaraJereczek @Mat_Guc @ZilliThomas @AnnaKirby17 @PBlanchardMD @achoud72 Pinging OA faculty @MKnoll_MD @_ShankarSiva @Icro_Meattini @seanmmcbride @NiuSanford @nataliagandur @acampsmalea @to_be_elizabeth

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David Sher
David Sher@DavidSherMD·
Absolutely incredible work by @_ShankarSiva and colleagues! Wow. My question is how to engage our surgical and medical oncology trialist colleagues to test this paradigm versus primary surgery. @Raquib_Hannan Is this going to end up like bladder cancer?
Shankar Siva@_ShankarSiva

#ESTRO26 - 📣 FASTRACKII final results, median F/U of 5 years. Thank you patients, funders, investigators - #kidneycancer #kcsm 1) 100% Local Control: No local recurrences were observed at 36, 60, or 84 months. 2) 100% Cancer-Specific Survival 3) Grade 3 AEs remain at 10%

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David Sher
David Sher@DavidSherMD·
Great concept to actually nail down what's happening in these fractions. So in the MRL-guided patients, it's just alignment and motion-management, so PTV margins are the same with and without daily adaptation? Dose/fraction? Are you stratifying by MR/CT and by QD versus QOD? Are patients blinded? Phenomenal idea. Need more of these kinds of studies to resolve how the (expensive and time-intensive) technology is really helping!
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David Sher
David Sher@DavidSherMD·
There are tremendous opportunities to improve post-operative radiotherapy in HNSCC. The DIREKHT trial is an excellent example of such work, in which they spared the contralateral neck in a specified group of patients and/or reduced the primary CTV dose to 56 Gy. The details are important, as over 60% of patients had contralateral (path-negative) neck dissections (from prior publication). Putting aside the controversy of sparing an un-dissected contralateral neck for an oropharynx (non-tonsil) or oral cavity cancer, there is still hesitance to spare a path-negative contralateral neck. This paper helps assuage those fears. In the original publication, there were 3 contralateral-only LN recurrences, all in un-dissected necks. That means there were zero solitary nodal recurrences in 92 patients with a path-negative contralateral neck dissection, now with long-term follow-up. If a contralateral neck has been adequately dissected and is negative, it's hard to justify additional treatment to that hemi-neck. It's difficult to judge the 56 Gy outcomes by abstract alone, especially since the cohort mixed HPV-positive OPC and oral cavity. Extremely informative trial!
OncoAlert@OncoAlert

Day TWO of #ESTRO26 Coverage by OncoAlert 🚨 De-intensification of postoperative radiotherapy in HNSCC by omitting contralateral elective neck irradiation– long term outcomes of the DIREKHT trial Presented by Charlotte Frei 🇩🇪 #RadOnc ☢️ The DIREKHT trial is a prospective multicentre phase II trial investigating de-intensified risk-adapted radiation in patients with newly diagnosed, non-metastatic HNSCC after surgery. A total of 140 patients were included in the analysis. After five years, overall locoregional recurrence rate was 6.0% (95% CI [1.9; 9.9]). Cumulative incidence of locoregional recurrence was 3.0% (95%-CI [0.1; 5.8]). Details on recurrence patterns and dysphagia rates are presented at ESTRO 2026. @ESTRO_RT @yasemin09896924 @LindaMrissa @christian_roenn @Valeriadionisi @gerryhanna @clchiang_hk @mtugceyilmaz @B_Tomasik @gmpetrianni @CiroFranzese1 @Atem84 @piet_ost @brachyexpert @BlanceS90 @The_PT_Explorer @BarbaraJereczek @Mat_Guc @ZilliThomas @AnnaKirby17 @PBlanchardMD @achoud72 Pinging OA faculty @MKnoll_MD @_ShankarSiva @Icro_Meattini @seanmmcbride @NiuSanford @nataliagandur @acampsmalea @to_be_elizabeth

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David Sher
David Sher@DavidSherMD·
JCOG 1208 is a nice study of ENI dose (46 Gy/23 fx) and volume reduction, without any solitary elective neck failures; another trial that supports ENI de-intensification. However, we cannot be satisfied with 79% locoregional PFS, especially for oropharyngeal cancer. Even with T1-2 N0-1 disease, sometimes concurrent chemotherapy may be needed.
OncoAlert@OncoAlert

Day TWO of #ESTRO26 Coverage by OncoAlert 🚨 Five-year follow-up outcomes from JCOG1208: A single-arm confirmatory trial of IMRT alone for early-stage oropharyngeal cancer Presenter Satoaki Nakamura 🇯🇵 JCOG1208 prospectively evaluated intensity-modulated radiotherapy alone for patients with early-stage oropharyngeal cancer and favorable performance status. At five years, overall survival was 88% and local progression-free survival was 79%, with durable disease control after de-escalated treatment. These results support two-step IMRT alone as a treatment option that may reduce chemotherapy-related burden while maintaining favorable long-term outcomes. #RadOnc @ESTRO_RT @yasemin09896924 @LindaMrissa @christian_roenn @Valeriadionisi @gerryhanna @clchiang_hk @mtugceyilmaz @B_Tomasik @gmpetrianni @CiroFranzese1 @Atem84 @piet_ost @brachyexpert @BlanceS90 @The_PT_Explorer @BarbaraJereczek @Mat_Guc @ZilliThomas @AnnaKirby17 @PBlanchardMD @achoud72 Pinging OA faculty @MKnoll_MD @_ShankarSiva @Icro_Meattini @seanmmcbride @NiuSanford @nataliagandur @acampsmalea @to_be_elizabeth

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David Sher retweetledi
OncoAlert
OncoAlert@OncoAlert·
Day TWO of #ESTRO26 Coverage by OncoAlert 🚨 Paradigm shift from bilateral elective nodal irradiation to SPECT/CT-based SNP to guide unilateral irradiation in HNSCC: multicenter prospective study Presented by Abrahim Al-Mamgani🇳🇱 SPECT/CT- and SN-guided selection tool for unilateral nodal irradiation (UNI) in patients with HNSCC is feasible, safe and very effective, as only 2 patients developed CRF (2.4%) with significant reduction of acute and late toxicity, compared to patients treated to both sides of the neck. Adding SNP to SEPCT/CT increased number of patients treated with UNI from 78% using only SPECT/CT to 91% by using combination of SPECT/CT- and SNP #RadOnc @ESTRO_RT @yasemin09896924 @LindaMrissa @christian_roenn @Valeriadionisi @gerryhanna @clchiang_hk @mtugceyilmaz @B_Tomasik @gmpetrianni @CiroFranzese1 @Atem84 @piet_ost @brachyexpert @BlanceS90 @The_PT_Explorer @BarbaraJereczek @Mat_Guc @ZilliThomas @AnnaKirby17 @PBlanchardMD @achoud72 Pinging OA faculty @MKnoll_MD @_ShankarSiva @Icro_Meattini @seanmmcbride @NiuSanford @nataliagandur @acampsmalea @to_be_elizabeth
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UTSW Radiation Oncology
UTSW Radiation Oncology@UTSW_RadOnc·
Our Senior Director of Clinical Physics, Dr. @MHLinPhD, presented a poster titled "Feasibility of Direct-to-Treatment Ultra-Hypofractioned Whole Breast VMAT using AI-Assisted CBCT-Guided Adaptive Radiotherapy," this morning at #ESTRO26.
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David Sher
David Sher@DavidSherMD·
Our field has to recognize that delivering the same treatment plan with protons instead of photons is not going to meaningfully move the needle in the (vast) majority of scenarios. Maybe it's slightly better here or there in a few domains (and in HN, there are still more randomized data to come), but we need to think deeper than just changing the beam in order to make the big improvements needed for our patients. What biomarkers allow us to modulate dose? Can we adapt the GTV over time? What is the appropriate elective dose and volume (if any...)? Can we further drop treatment margins? Can we be more creative with dose and fractionation? Are we stuck with cisplatin forever? There are so many questions to address and opportunities to advance the therapeutic ratio of radiotherapy: we can't get bogged down by the proton versus photon question.
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Nadeem Riaz
Nadeem Riaz@xrtGenomics·
Stay tuned! Informally we see some differences in acute toxicity (mainly dysgusia) that attenuate over time. The controversey isn't on this though (UK & MDA data are consistent here) -- its on the OS data without a PFS benefit, with a lot of obivous statistical confounding issues.
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Nadeem Riaz
Nadeem Riaz@xrtGenomics·
Great letter by @SeanMcbride laying out real concerns with the OS claim in @SJFrankMD's proton vs. photon oropharynx trial. Compelling enough that Yingzhi Wu and @EChrisDee pulled our own data. We see no OS difference between protons and photons. Together with UK TORPEdO RCT, this adds to the concern that the randomized trial’s OS finding may be hypothesis-generating rather than causal.
Nadeem Riaz tweet media
Sean McBride@seanmmcbride

Our letter to the editor in The Lancet critiquing the MD Anderson-led trial of protons v photons for OPC. Appreciate @SJFrankMD's well thought out response. I think we can all agree on two points: 1) Steve deserves major kudos for bringing level 1 evidence to the debate on protons v photons for OPC. These trials are extraordinarily difficult to run, and Steve, et al pulled it off. Well done! 2) Longer term follow-up from TORPEdO will help tease out the extent to which protons improves OS in OPC. @CJTsaiMDPhD @drlorenmell @xrtGenomics @DavidSherMD #radonc #hncsm thelancet.com/journals/lance…

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David Sher
David Sher@DavidSherMD·
We also need to remember that the goal of de-escalation is not just to lower the nominal dose but improve quality-of-life outcomes. In this study, 37% of *de-escalated* patients had a g-tube! That’s a lot. We don’t know any of the radiation dosimetry from a radiation de-escalation trial. In addition, there was a menu of dose de-escalation options… how were these patients treated? How many actually received 66 Gy, and not 60 Gy? Please share!! Overall, tremendous kudos should go out to the DFCI team for completing such an important trial. The data are absolutely crucial for the community to figure out the next steps in bioselection for de-escalated treatment. However, it looks like that for baseline favorable patients, the biomarker doesn’t help much, so we need to generate additional ideas on how to select this population. Baseline genomic testing for radiosensitivity? Imaging-based response? A different circulating biomarker? All are possible, but as this study showed, you need to test the concept prospectively to see if there is true utility. One final note: the updated UNC data at 60 Gy are extremely favorable, as are the DFCI results, and HN002. We really need to see the granular data from HN005 to see what went wrong!
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David Sher
David Sher@DavidSherMD·
Consider that 35% of low-risk patients did not achieve >95% clearance by week 4-5, but none of them recurred. Of the 65% of low-risk patients who achieved > 95% clearance, 3 recurred. The two de-escalated intermediate-risk patients who recurred also achieved 95% clearance. So what can we take from these results? First, it appears that NavDX doesn’t add much to baseline low-risk decision-making. If you relied on clearance to go down to 60 Gy, you would have missed an opportunity to de-escalate for many patients while still reducing dose to the patients who progress. This paradigm does not yet add enough to the low-risk population to inform decision-making. Who knows if it ever will? A more sensitive biomarker will just capture more patients who probably will do well at a lower dose… On the other hand, I would argue that the greatest utility thus far for the biomarker is identifying patients at intermediate-risk who typically would NOT be considered for dose reduction but yet may very well benefit from some degree of de-intensification. To me, that is very exciting. Is it as exciting at using F-MISO PET-CT and going down to 30 Gy? No, but it’s more feasible and straightforward. I would love to see this concept fleshed out further for this intermediate-risk population.
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David Sher
David Sher@DavidSherMD·
Exciting to see this novel trial of biomarker-driven HPV+ de-escalation come out! There is a lot to learn here, but there are details in the trial that aren’t immediately obvious.
Glenn J. Hanna, M.D.@HeadNeckMD

Sharing the results of ReACT 1.0 in @NatureComms -- the first study to use HPV ctDNA to guide CRT de-escalation in higher risk HPV+ OPC. ctDNA metrics may improve risk stratification. Grateful to our coauthors. @Naveris_inc @DanaFarberNews @jdschoenfeld1 nature.com/articles/s4146…

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Keşfet

@PaulJiL @ASCO @drlorenmell @OncoAlert @brunolarvol @_ShankarSiva @neildwallaceie @PeterMacRadOnc