Delighted to present my oral presentation on “Pan-Cancer Analysis of 4-1BB Transcriptome Expression and Its Impact on Outcome in Patients Treated with ICIs” in the Developmental and Precision Medicine session at
#ESMOAsia23
. Special thanks to
@Dr_R_Kurzrock
&
@myESMO
!
🔥 HOT OFF THE PRESS from our study
@JTOonline
: the timing of ICI infusions may affect survival in locally advanced NSCLC patients. Early infusions lead to better outcomes than late ones. A first look at ICI chrono-modulation in non-metastatic cancers. 🕒
🚀 Exciting news! Building on our research (JAMA Netw Open), National Cancer Center Hospital, Chugai Pharma, Osaka Medical and Pharmaceutical University, & MICIN launched Japan's first company-sponsored Phase I oncology decentralized clinical trial.
Fantastic talk with Dr.
@DoctorJSpicer
& Dr. Maqueda on preoperative RWD cases in Canada. Incredibly insightful for thoracic surgeons and medical oncologists. Honoured to meet you both!
@haigan_geka
🔬 Key Findings on Pathogenic Germline Variants (PGVs) in Lung Cancer:
1. 15% of patients have PGVs.
2. PGV frequency isn't impacted by family or personal history of other cancers.
3. 60% of PGVs are in actionable DNA damage repair genes.
@JCO_ASCO
#LCSM
Thrilled to announce that I've been awarded a grant by Chugai Pharma as a PhD candidate! It's an honor to receive this prestigious support, and I'm incredibly grateful for the opportunity.
Exploring De Novo EGFR T790M in NSCLC🇨🇳:
・Found in ~1% of NSCLC.
・ Coexists with L858R mutation ➔ 🔽 outcomes with 3rd-gen TKIs.
・Alone, de novo T790M's oncogenicity is limited, but increases with common EGFR mutation. What's its mechanistic role ? 🤔
Key findings on EGFR T790M carriers:
・> 50% diagnosed with lung cancer by 60.
・Lung nodules common in non-cancer patients.
・They often have somatic EGFR mutations.
・Study lacked Asian participants; more research needed.
・EGFR-TKI might be a risk-reducing strategy.
Wow, the NCI is exploring both ImmunoMATCH and ComboMATCH! In my opinion, we should make use of not just in vitro data but also human studies like I-PREDICT or OmniSeq analysis led by
@Dr_R_Kurzrock
to select drug combinations.
"The New NCI Precision Medicine Trials" - just published in
@CCR_AACR
on the latest precision medicine efforts
@theNCI
.
You can read about these 2nd generation precision medicine trials - ComboMATCH, iMATCH, and myeloMATCH - here:
#CancerResearch
#NCTN
Our research, published in
@JAMANetworkOpen
, was featured in The ASCO Post News—a great honor. We found that longer travel times reduced the likelihood of patients participating in genotype-matched trials. via
@ascopost
Sotorasib, the Poster Child for Project Optimus: Truths & Fantasies 🧐. Outside the US, given PK, efficacy, cost (national health insurance) & toxicity, opting for 240mg seems a wise choice 💡. A single 960mg ($21,000/mo) prescription could last 4 months.
Very Important research by Dr.
@mollylisc
from 🇭🇰: Recurrent ILD 🫁 risk higher with Osi rechallenge (63%) vs. erlotinib (11%). Clinically Relevant for 🇯🇵 pts. Erlotinib suggested for Osi-induced ILD.
@JTOonline
The cost of 3.5-year recent cancer drugs ($700,000) is approximately half of the average lifetime salary in Japan. It’s unsustainable for our national health care system to provide these novel drugs to all patients. Younger generations will bear the burden.
Findings of this study indicate that the median annual price of anticancer drugs in the US is not associated with the novelty of their mechanism of action.
The abstract, "Pan-cancer analysis of 4-1BB transcriptome expression and its impact on outcomes with ICIs," was chosen for a mini-oral and ESMO Asia travel grant. Thrilled! Huge thanks for the incredible opportunity and support
@Dr_R_Kurzrock
@OmniSeq
@zacksurg
@jacobadashek
A new WHO🌍 report reveals lung cancer as the top global cancer (2.5M new cases 📈) & leading in deaths (1.8M📈). Notably, it's the 2nd most common cancer among women👩 in both cases & deaths. A lesser-known fact many are unaware of.
#lungcancer
#LCSM
🔍 The cfDNA & multitarget stool DNA tests in NEJM are buzzing topics! While sensitivity for precancerous lesions is low, tech brilliance 🧠 will solve this challenge. Should this breakthrough hit lung cancers, how to intervene with premalignancy becomes crucial for patients.🫁
Hot off the press! “Multi-omics” approach (genomics, epigenomics, proteomics) to plasma testing proves effective in colorectal cancer screening. Hoping same will be seen in other cancer types
@NEJM
@ASCO
@isliquidbiopsy
490 NSCLC pts in NGS Testing at Tempus Labs.🧬 Variant Concordance: 66%. Unique variants: 29% found in tissue, 5% in ctDNA➡️Most assay-unique variants (>70%) detected by tissue testing. 📌Tissue is Still the issue in NSCLC!
@JAMANetworkOpen
My colleague, Dr. Kato from National Cancer Center Hospital East, will discuss the efficacy of ICI+chemo doublet vs. chemo for HER2-mutant NSCLC (268 pts) at LC-SCRUM Asia (15,251 pts). He'll address a crucial question 🤔: the optimal 1st-line Tx for HER2-mutant NSCLC.
#JSMO2024
🎉 Excited to share I've been selected for the Honjo International Scholarship Foundation's 28th cohort!! With a 1 in 60 acceptance rate, it's a prestigious honor. Huge thanks to the National Cancer Center, Komagome Hospital, and TMDU for their support.
⭐️JSMO2024 Early Career Oncologist Lounge
@JSMO_official
📣You can meet Dr. Lynn M. Schuchter
@ASCOPres
, President ASCO
@ASCO
, to ask questions, network, and receive career advice in the field of oncology.
🗓️Feb 23, 11:30~12:30
#JSMO2024
My twin brother, a researcher in Dr. Aviv Regev's Lab at Genentech (gRED) 🧬, is seeking a summer research intern. 🌟 There are numerous opportunities for top journal publications, combining AI with biology/medicine for drug discovery 🧪
🔬Research from the Breast TRACERx study on TNBC 🎀reveals that chromosomal instability🧬 (marked by a high frequency of LOH and WGD) leads to diverse subclones and immune evasion through mechanisms like HLA LOH and ecDNA-driven immune suppression.
@AACR
The RAGNAR study underscores the clinical benefits of selective FGFR inhibitors in a tumor-agnostic context, yet the ORR remains at 30%. Our findings
@Dr_R_Kurzrock
@jacobadashek
suggest that targeting co-alterations, such as FGFR and CDK4/6, could potentially enhance efficacy.
NEW: In the RAGNAR single-arm ph2 trial of erdafitinib in pts w/ adv solid tumours with FGFR alterations, an objective response was seen in 64 (30% [95% CI 24–36]) of 217 patients across 16 distinct tumour types (median FU 17·9 months [IQR 13·6–23·9]).
Abstract titles for
#ASCO23
released
@ASCO
Will be presenting a poster on our data from
@NccriOfficial
on "Impact of patient travel time on disparities in precision oncology clinical trials."
I'm excited to attend the annual meeting in Chicago!
I just rewatched Chris Abbosh's keynote lecture on Molecular Minimal Residual Disease and Early Detection. The concept of combo of ctDNA and pCR status, as well as TNM(B) staging, is very insightful.
#ASCOBT23
Great summary of MCED: Over half of the patients with positive results in recent studies had no discernible cancer, yet they faced numerous risks of diagnostic procedures. This highlights a significant unmet need in MCED.
@ASCO
Daily News
Must read for young physician-scientist. "Young investigators in particular might have the greatest impact probing deeply Check for updates nature cancerTurning points where there is space to grow. Even graveyards, left fallow, can be fertile fields."
Why Osaka Medical and Pharmaceutical University (OMPU) is chosen as a satellite🏥? Find out in our prior paper. With a travel time of over 2 hours from OMPU (Osaka) to NCCH (Tokyo), Decentralized Clinical Trials could significantly reduce travel burdens.
@StephenVLiu
Thank you so much for tweeting about our study! Although there are many confounding factors and potential publication bias, it's worthwhile to investigate the mechanism of ICI chronotherapy.
Our new
@ASCO
#ASCO23
abstract released today asks an important question in the era of precision oncology: "Do regional disparities create inequities in precision oncology?" → YES. DCT (decentralization of clinical trials) is needed. to solve the problem.
Check out our editorial on ICI therapy for fusion-positive NSCLC (IMMUNOTARGET registry). It highlights the ineffectiveness of ICI in ALK/RET/ROS1 fusions and emphasizes the importance of accurate diagnostic methods for these rare subsets to avoid false positives by IHC or FISH.
Reflex testing has boosted the success rate of DNA tissue-based molecular testing 🫁. Japan lacks such a system, requiring oncologists to manually order tests via paperwork each time. We need the system to ensure Right drug-Right patient-Right time.
#LCSM
🔥🚨Hot off the press👉Increased travel time was associated with a reduced chance of genotype-matched trial participation after CGP testing. 👉Regional disparities in precision oncology👉Need for solutions like DCT to ease the travel burden.
Longer travel times were associated with a decreased likelihood of participation in genotype-matched trials. Regional disparities perpetuate inequities in
#PrecisionOncology
.
@DrYujiUehara
@NccriOfficial
In the upcoming NCI-ComboMATCH trial, combinations are limited to 'targeted therapies'. While I concur with the importance of exploring combinations with immunotherapies, I'm concerned about potential toxicity variations across different tumor types.
The NCI-MATCH trial: lessons for precision oncology
@NatureMedicine
👏Very innovative
👉1,593/6,000 pts assigned to 38 subtrials
👍pos. signal in 7/27 subtrials
👉Proof of concept > we need to continue this pass to improve outcome & tackle 💊resistance
Due to a high treatment-related death rate (7.4%, n = 11/148) in an early-terminated trial, Japanese oncologists are wary of using the 9LA regimen (platinum-doublet 2 cycles with nivolumab + ipilimumab) for metastatic lung cancer.
Interesting letter to the editor
@Annals_Oncology
reports high rate of cytokine release syndrome
#CRS
and irAEs with nivolumab + ipilimumab for NSCLC in Japan. JCOG2007 trial stopped for high rate of treatment-related deaths. Pharmacogenomic differences?
Healio has featured our study! We're honored to have our work recognized in the US medical media. "Travel time linked to participation in genotype-matched cancer trials "
@GoHealio
Read our editorial on BRAF RNA expression in lung adenocarcinoma. Approximately 75% of LUAD patients displayed 🔼 BRAF RNA expression, correlating with 🔽 prognosis to platinum doublet therapy. A deeper grasp of RNA expression beyond DNA is needed.
@mollylisc
@JTOonline
In our institution, we frequently transition from Osi to Afa or Gefi because we experience a higher incidence of severe ILD associated with the Osi rechallenge. This anecdotal evidence is confirmed in your paper!!
Just out! We reported the successful treatment of ALK+ LCNEC with sequential ALK inhibitors. Emphasizing the importance of NGS for LCNEC patients, especially younger patients.
#LCSM
@JTOonline
Data from LC-SCRUM-Asia
@JTOonline
describes
#BRAF
mutant NSCLC. Overall, 3.5% had a BRAF mutation (30% of which were class 1: V600E). mPFS with chemotherapy 11.5m and mOS 34.8m. Non-V600E mutations were more common in this Asian cohort.
Physician motivation and knowledge gaps between referring and early drug development doctors are significant barriers to enrollment. We need a system to identify and prioritize patients for referral.
Molecular targeted trial w/identified potentially eligible patients within feasible distance failed to enroll; findings raise the hypothesis that the biggest barrier to enrollment is motivation of treating physicians.
🔍 Interesting study: The number of ctDNA mutations, plasma DNA concentration, and clinical factors can predict outcomes in RRMM. TP53 mutation has different meanings between BMPC and ctDNA. We may say the same thing in the lung cancer space. 🫁
Happy to share our latest paper from
@BloodJournal
.
@yasunori_kogure
and colleagues analyzed relapsed/refractory
#multiple_myeloma
(RRMM) and found that molecular profiling with
#ctDNA
mutations can enhance patient management strategies for RRMM.
Insightful summary on cancer screening status. PATHFINDER study shows MCED test detected cancer in 1.4% of 6,621 people, but only 38% of positives were confirmed - a high false-positive rate. Much work needed for clinical implementation."
Clinical trials assess a precision-medicine approach to cancer screening.
News feature from
@sofiamoutinhoBR
, part of our focus on Building Healthy Populations.
News and Views:
@masakanai
explains how fine-scale population structures can unveil crucial insights into healthcare disparities. Part of our focus on Building Healthy Populations.
@broadinstitute
@MGH_RI
Early-Stage Lung Cancer: Using Circulating Tumor DNA to Get Personal. .
・Two ways: Tumor-informed (NGS) vs. Tumor-agnostic (DNA methylation, cfDNA fragmentation).
・ Most NSCLC studies used the former way.
・ Main issue: Low negative predictive value.
Must read on the integration of AI and conventional statistical methods. Many formats of protocols focus solely on conventional stats, which can be frustrating sometimes. 'Where Medical Statistics Meets Artificial Intelligence' | NEJM "
Facing hurdles in MCED🩸: 1️⃣ Blood sampling skews towards hematologic cancer signals. 2️⃣ Most detected solid tumors: late-stage or recurrent. 3️⃣ Many positive results, but no identified cancer. 4️⃣ Only <1/3 of cancers diagnosed were detected by MCED.
Men face a higher risk of lung cancer from household PM2.5 exposure than women, including in Asia. Last year,
@CharlesSwanton
reported the link between PM2.5 and EGFRm NSCLC. Yet, unknown factors may increase women's risk for this cancer
@JTOonline
#LCSM
@stephanieplsaw
@danieltanmd
Congratulations on your paper! The focus on not only MRD but also accessibility is excellent, and the findings are highly relevant to many Asian countries!! Is monitoring tumor markers a common practice in SG? (It's a standard in Japan.)
🔬Outstanding paper: In allogeneic CAR T cells, 3 genes were silenced via base editing:
1. T-cell receptor β chain: Reduces T-cell receptor expression & graft-versus-host effect.
2. CD52: Enables anti-CD52 immunosuppression.
3. CD7: Targets only tumors, not CAR T cells themselves
Original Article: Base-Edited CAR7 T Cells for Relapsed T-Cell Acute Lymphoblastic Leukemia
Science behind the Study: Engineering CAR T Cells for Off-the-Shelf Use