Dr. Rafael Herrera García 🇻🇪🇩🇴

Oncólogo Radioterapeuta/
Jefe de servicio LDCC-IOHP
CDD Radioterapia Clínica Abreu

[Dr Rishabh Jain @DrRishabhOnco]

🧠🩺 Onco-Nephrology is no longer optional. It is essential.

Cancer patients are living longer.
Kidney toxicities are rising.
Decisions are getting harder.

This excellent CKJ review lays out 10 practical tips for running an effective onco-nephrology clinic 👇

🔹 Measure GFR correctly
Creatinine alone misleads. Combined Cr + Cys or measured GFR changes dosing, eligibility, and toxicity risk.

🔹 Not every creatinine rise = AKI
Many TKIs and targeted agents cause pseudo-AKI by blocking tubular secretion. Do not stop effective cancer therapy blindly.

🔹 VEGF inhibitors hit the kidney spectrum
HTN → proteinuria → TMA. Early nephrology input prevents irreversible damage.

🔹 ICI-AKI is usually steroid responsive
Early steroids improve recovery. Biopsy matters in complex cases to avoid over or under treatment.

🔹 Steroid-refractory ICI-AIN exists
Infliximab is emerging as a key steroid-sparing option in selected patients.

🔹 Transplant patients are not excluded anymore
With optimized immunosuppression, ICIs can be effective with acceptable rejection risk.

🔹 Plasma cell disorders deserve early transplant referral
MM and AL amyloidosis patients on dialysis can achieve meaningful survival post kidney transplant.

📌 Bottom line
The goal is not just kidney rescue.
It is safe continuation or timely re-initiation of cancer therapy.

#OncoNephrology #MedTwitter #Oncology #Nephrology #CancerCare
@OncoAlert @ASCO @ESMO_Open @myESMO

[Dr Rishabh Jain @DrRishabhOnco]

🔥 ASH25 Update: Plasmablastic Lymphoma (PBL) treatment pathway simplified

🧬 What makes PBL unique
🧪 Distinct, highly aggressive lymphoma
🧫 Strongly associated with EBV
🧬 Often carries MYC rearrangement
🔍 Requires high clinical suspicion + expert pathology

📌 Treatment algorithm
🟩 HIV positive / HIV negative
Early stage ➜ CHOP x4 + XRT
Advanced stage ➜ EPOCH x6 + XRT

📈 Response assessment
❗ Less than CR ➜ Salvage chemo → ASCT
✅ Complete response ➜ Surveillance ± ASCT

💡 Evolving front line ideas
💊 Bortezomib or daratumumab with chemo may improve outcomes
🎯 PDL1 and BCMA targeted therapies show promise in relapsed settings

✨ Takeaway
PBL needs aggressive upfront therapy, early consolidation, and integration of novel immune targeted options.

#OncoTwitter #MedTwitter #ASH25 @OncoAlert @myesmo @esmo_open @ASCO

[Heart Rhythm Case Reports @HRS_CaseReports]

Ventricular Fibrillation Triggered by Cavotricuspid Isthmus Radiofrequency Ablation with a Dual-Energy Lattice-Tip Catheter in a Patient with an Implantable Cardioverter-Defibrillator
@SCYap77
https://t.co/1gJ9RVPIZe

[Dr Rishabh Jain @DrRishabhOnco]

🫀 ADT choices and cardiovascular risk in prostate cancer
#GlobalForum25 #PROSCA25

Men on ADT live long enough for CVD to become a major competing risk. Today’s reminder hits hard for daily practice.

💡 EAU 2024 says
Patients with pre existing CVD or strong CV risk factors may be better treated with GnRH antagonists if chemical castration is planned.

💊 HERO trial insights
Regulatory antagonist (relugolix) showed:
😮‍💨 2.9 percent MACE vs 6.2 percent with leuprolide
In men with prior MACE, difference was 3.6 percent vs 17.8 percent.

🧬 Why antagonists may be safer
No flare
Faster testosterone suppression
Less endothelial stress and inflammation signals

📌 Clinical takeaway
Cardiovascular health should guide ADT choice.
Take note, monitor, and manage CV risk at every visit.

#OncoTwitter #MedTwitter #ProstateCancer #GU25
@OncoAlert @myesmo @esmo_open @asco @mirrorsmed

[JAMA Oncology @JAMAOnc]

This JAMA Oncology Patient Page describes the 3 main types of urinary diversions and care required after surgery to ensure an active and fulfilling life. https://t.co/ccimk5e5fE

[Nieves Martinez Lago MD PhD @DraMartinezLago]

🧬 Atezolizumab + bevacizumab in MSI-like mCRC (phase II)
🎯 ORR 38.6% in the MSI-like cohort
🔥 MSI mCRC: ORR 65.2%
⚠️ MSS mCRC: ORR 9.5% (mainly without liver mets)
⏳ Median PFS: 23.2 mo (MSI) vs 4.0 mo (MSS)
💡 MSI-like GES does not enrich for sensitivity beyond standard MSI

🔗 https://t.co/YHWcnkmycE

[Dr Rishabh Jain @DrRishabhOnco]

🧠✨ STELLAR Trial (JCO 2025): A Big Win for Recurrent IDH-mut Grade 3 Astrocytoma

🚨 Huge neuro-oncology update!
Adding Eflornithine + Lomustine shows major survival gains but only in the right molecular group.
Let’s break it down 👇🧬

🎯 Trial Essentials
📌 Phase III, randomized, open-label
👥 343 patients, recurrent grade 3 astrocytoma
💉 Prior RT + TMZ

🔀 Arms:
•💊 Eflornithine + Lomustine
•💊 Lomustine alone

🎯 Primary endpoint: OS

🧠 Reclassified per WHO 2021 into:
•IDH-mut Grade 3
•IDH-mut Grade 4 (CDKN2A/B del)
•IDH-wt GBM

🔥 Key Results (IDH-mut Grade 3 - the REAL target group)
✨ Defined before unblinding as the biologically appropriate subset

🕒 OS: 34.9 vs 23.5 months
➝ +11.4 months ⭐
➝ HR 0.64

🧭 PFS: 15.8 vs 7.2 months
➝ >2× improvement 🚀
➝ HR 0.57

📈 Higher radiographic responses
⚠️ No benefit in IDH-mut Grade 4 or IDH-wt GBM (expected for cytostatic therapy)

🧬 Mechanism (Why it Works)
Eflornithine = ODC inhibitor ❌🧪 polyamine synthesis
👉 Cytostatic, not cytotoxic
👉 Works best in slower-growing IDH-mut Grade 3 tumors
👉 Perfect biological match with the results

⚠️ Safety (Manageable)
•🩸 Myelosuppression: 42% vs 29%
•👂 Hearing impairment: 24% vs 0% (mostly reversible)
•🤢 Diarrhea, nausea, fatigue (expected)
•❗No grade 5 events

📌 Takeaway
For recurrent IDH-mut Grade 3 astrocytoma
➡️ Eflornithine + Lomustine = meaningful survival advantage 🧠💪
A potential new option in a setting with very limited therapies.

📖 Full paper in comment ⬇️

#OncoTwitter #MedTwitter #NeuroOncology #Glioma
@OncoAlert @myesmo @esmo_open @ASCO @JournalofCO

[Dr Rishabh Jain @DrRishabhOnco]

🚀 New hope for atypical EGFR mutations in NSCLC?

Amivantamab + Lazertinib delivers strong results in CHRYSALIS-2 🧬🔥

🧪 Population (n=105)

Atypical EGFR mutations only (G719X, L861X, S768I, etc.)
No Ex19del / L858R / Ex20ins overlap.

🎯 Key Results

Overall
• ORR: 52%
• mPFS: 11.1 mo
• mDoR: 14.1 mo
• mOS: NE

Treatment-naïve
• ORR: 57%
• mPFS: 19.5 mo 🤯
• mDoR: 20.7 mo
• 24-mo OS: 77%

Previously treated
• ORR: 48%
• mPFS: 7.8 mo
• mOS: 22.8 mo

🧬 Mutation subsets

• PACC: ORR 45%
• Classical-like: ORR 64%
• T790M-like: ORR 67%

⚠️ Safety
Mostly Grade 1–2.
Common: rash, paronychia, hypoalbuminemia, IRRs.
VTE: 30% (mostly ≤4 months) → Prophylactic anticoagulation now recommended.

💡 Takeaway
Atypical EGFR tumors are tough.
This is the largest prospective study in this population - and Amivantamab + Lazertinib shows clinically meaningful, durable activity, especially first-line.

📖 Full paper in comment ⬇️

#OncoTwitter #MedTwitter #LCSM #ESMO25
@OncoAlert @myesmo @esmo_open @ASCO @JournalCancer @JTOonline

[Dr Rishabh Jain @DrRishabhOnco]

🔥 New JAMA Oncology study: The hidden burden of metastatic recurrence in AYAs (15–39 yrs)

Even without metastasis at diagnosis… 1 in 10 adolescents & young adults STILL develop metastatic recurrence.

And survival is often worse than de-novo stage IV.

🎯 Key Findings (48,406 patients, 2006–2018)

📌 5-year metastatic recurrence (after early-stage diagnosis):
•Sarcoma: 24.5%
•Colorectal: 21.8%
•Cervical: 16.3%
•Breast: 14.7%
•Stage III (all cancers except thyroid): >30%

📈 Cervical cancer recurrence is rising - from 12.7% → 20.4%
📉 Colorectal & melanoma recurrence falling over time.

💀 Survival after metastatic recurrence vs metastatic at diagnosis

Worse in almost every cancer type:
•Breast: HR 2.87
•Cervical: HR 2.10
•Melanoma: HR 1.61
•Sarcoma: HR 1.57
•Colorectal: HR 1.53

🔥 Only testicular & thyroid cancer were exceptions.

Late recurrence (≥24 months) = better prognosis in breast/cervix
Late recurrence = worse in testicular/thyroid.

🧠 Why this matters?
AYA survivors often “graduate” from oncology follow-up early.
But this data shows:

Metastatic recurrence is common, deadly, and varies hugely by cancer type + stage.

This is a survivorship problem, not just a treatment problem.

A must-know dataset for oncologists, registries, policy makers, and AYA survivorship programs.

📖 Full study in comment ⬇️

#OncoTwitter #AYAOncology #CancerSurvivorship #CancerEpi #OncologyResearch
@OncoAlert @ESMO_Open @myESMO @ASCO

[Dr Rishabh Jain @DrRishabhOnco]

🔥 Did we finally find the subgroup of HR+/HER2− patients who actually respond to immunotherapy?

A new Nature Communications pilot trial tested neoadjuvant nab-paclitaxel + pembrolizumab with a 2-week chemo-first vs ICI-first run-in.

Here’s what stood out 👇

🌸 29 patients, mostly node-positive
🎯 Primary endpoint missed — PD-L1 didn’t increase post run-in
💥 pCR = 17%, but biology mattered:
• CPS <1 → 0%
• CPS ≥1 → 28%
• CPS ≥10 → 43%

🧬 Favorable responders = “inflamed biology”
↑ IFN-γ
↑ Allograft rejection
↑ CD8+ T cells, M1 macrophages

🧬 Poor responders = “estrogen-driven biology”
↑ Estrogen-response genes
↓ Antigen processing/presentation
→ A clear immune-escape signature

💊 Safety: No new signals (13% grade 3-4 irAEs)
⏳ 3-year EFS: 86%

🔥 Key Takeaway:
HR+/HER2− isn’t uniformly immunogenic but a biologically distinct subgroup (PD-L1 high + inflamed TME) may benefit from ICI.
Estrogen-high tumors appear intrinsically resistant.

📌 Implication: Better biomarkers → better selection. Sequencing (chemo-first vs ICI-first) needs more data.

🔖 Save for exam prep & journal club!
📖 Full paper in comment ⬇️

#OncoTwitter #BreastCancer #Immunotherapy #MedTwitter @OncoAlert @myESMO @esmo_open @ASCO @stolaney1

[Daniel Castellano @cdanicas]

🎯🎯.- How to apply the current evidence in the treatment of mCSPC!! Excellent review.🙌
https://t.co/OFccsZ439w

👉.- The new molecular precision "triplet intensification" is here.
👉.- A HRR (BRCA2+) alt and pTEN loss population have a poor prognosis.
👉.- We need to better biomarkers profile in this setting
@OncoAlert @APCCC_Lugano @ANZUPtrials @myESMO @GuardConsortium @fedelosco

[Dr Rishabh Jain @DrRishabhOnco]

🚀 KRAS: From “Undruggable” to the Hottest Target in Oncology 🔥🧬

KRAS is the most mutated oncogene in cancer - yet for decades it was “undruggable.”
2025 marks a turning point.

A brand-new Signal Transduction & Targeted Therapy review lays out the ENTIRE evolution:
• Why KRAS drives PDAC, CRC, NSCLC
• Why G12C inhibitors work but only partly
• Why resistance is inevitable
• What the next wave of KRAS therapies looks like

🔑 Key takeaways:

🧩 KRAS mutations = ~30% of all cancers
– PDAC: 80–90%
– CRC: ~40%
– NSCLC: ~20% (G12C dominant)

🧬 Approved “OFF-state” inhibitors:
•Sotorasib
•Adagrasib
➡️ ORR ~30–40%, PFS ~6 months.
➡️ Resistance? Guaranteed.

🔥 Major resistance mechanisms:
– Secondary KRAS mutations (Y96D/S, G13D, A59…)
– RTK pathway upregulation
– EMT & squamous transformation
– KRAS amplification
– KEAP1/STK11/TP53 co-mutation biology

💡 The future = multi-modal KRAS targeting:
– Pan-RAS inhibitors
– G12D inhibitors (MRTX1133-like)
– SOS1/SHP2 inhibitors combos
– KRAS degraders (PROTACs)
– KRAS vaccines & cell therapies
– RNA & antisense therapeutics

🧠 The review beautifully shows KRAS as a signaling “master switch” with MAPK, PI3K, Ral, RAC1, Hippo/YAP-TAZ crosstalk explaining why single-agent inhibition fails.

🎯 Bottom line:
KRAS is no longer undruggable - it’s just very hard to drug.
The next breakthroughs will come from combos + pan-KRAS + epigenetic modulation + TME targeting.

🔖 Save this - it’s THE 2025 roadmap for KRAS-targeted therapy.
📖 Full paper cited below.

#OncoTwitter #MedTwitter #LCSM #GIOnc #TargetedTherapy @myESMO @OncoAlert @ESMO_Open

[Oscar Arias @OACerebro]

Guía básica para leer una revisión sistemática + metaanálisis y aplicar los resultados a los pacientes.

Una guía obligada para los profesionales de la salud.

https://t.co/uGgEd3p9BF

[Pierre Blanchard, MD @PBlanchardMD]

Practical step by step guidance on how to perform pancreatic #SBRT by @lauren_henke at #SABR2025

#SBRT is the best way to deliver BED&gt;100Gy to this tumors, which likely drives superior survival in #PancreaticCancer

[JAMA Oncology @JAMAOnc]

Among patients with advanced urothelial cancer, upfront enfortumab vedotin dose reduction was linked to a 50% reduction in treatment interruption risk but did not compromise overall survival. https://t.co/0vqWHuJ9tm

[Dr Rishabh Jain @DrRishabhOnco]

🫀 ICI Cardiotoxicity - What Every Oncologist Must Know

IC-OS Position Statement | JAMA Oncology 2025

⚡ Key CV Toxicities
❤️ Myocarditis
💥 Arrhythmias (AF, VT, CHB)
🫁 Pericarditis
💔 HF ± inflammation
🧠 ACS & stroke (accelerated atherosclerosis)

🔥 Myocarditis = Highest Concern
•Incidence: 0.75 percent single ICI | 1 to 2 percent dual ICI
•Fatality improving but still serious
•Peak window: first 90 days

🎯 Who Is High Risk?
•Dual ICI therapy
•Thymic tumors
•Pre-existing autoimmune disease
•Anti-AChR antibodies
•Older adults

🧪 Diagnosis
•Troponin + ECG first
•Always rule out ACS
•CMR for confirmation
•EMB for unclear/urgent cases

💊 Management
Nonsevere: stop ICI, high-dose IV steroids → slow taper
Severe: ICU, 1000 mg methylpred, early abatacept, ± ruxolitinib/IVIG/PLEX, MCS if needed

🔄 Rechallenge
•Only after full resolution
•Prednisone ideally <10 mg/day
•Prefer PD-1/PD-L1 monotherapy
•Close biomarker monitoring

🧭 Takeaway
Early suspicion + cardio-oncology teamwork saves lives.
Keep myocarditis high on the radar.

🔖full paper in comments below ⬇️

#OncoTwitter #MedTwitter #CardioOncology #Immunotherapy #ICI #CancerResearch

@myesmo @esmo_open @ASCO @OncoAlert @JAMA_current

[Applied Radiation Oncology @Applied_RadOnc]

The Use of Adaptive Radiation in a Retroperitoneal Seminoma Patient with Poor Candidacy for Chemotherapy: A Teaching Case

🔗 https://t.co/wdm9wI1s2p

#radonc #radonced #menshealth #movember

[Dr Rishabh Jain @DrRishabhOnco]

🎯 Belzutifan breaks new ground in rare neuroendocrine tumors!
#LITESPARK015 | #NEJM | #ESMO25

🧠 Advanced pheochromocytoma / paraganglioma (n = 72)
💊 Belzutifan 120 mg QD

📈 Results:
• ORR 26 % (95 % CI 17–38) – all partial responses
• Disease control 85 %
• Median DOR 20.4 mo | PFS 22.3 mo
• 32 % reduced ≥ 50 % of antihypertensive dose
• OS 76 % at 24 mo
• Main AE: anemia (88 %, G3 22 %)

🩸 Takeaway:
Durable tumor and BP responses with manageable safety → HIF-2α inhibition emerges as a real option for metastatic pheo-para!

📖 Full paper: Jimenez et al. NEJM 2025.
🔗 https://t.co/CUpq6rXDMs

#OncoTwitter #EndocrineOncology #Belzutifan @NEJM @esmo_open @OncoAlert @myesmo

[Dr Rishabh Jain @DrRishabhOnco]

🎯 KEYNOTE-905 (EV-303): Setting a New Standard in Cisplatin-Ineligible MIBC! 💥

💊 Arms:
🔹 EV + Pembrolizumab (Perioperative)
🔹 RC + PLND (Control)

🧪 Population: Muscle-invasive bladder cancer (T2–T4aN0M0 / T1–T4aN1M0)

80% cisplatin-ineligible (Galsky criteria)

📊 Results:
✅ EFS: NR vs 15.7 mo | HR 0.40 (95% CI 0.28–0.57; P<.001)
✅ OS: NR vs 41.7 mo | HR 0.50 (95% CI 0.33–0.74; P<.001)
✅ pCR: 57.1% vs 8.6% (Δ 48.3%; P<.001)
⚠️ Gr ≥ 3 AEs: 71% (EV+pembro) vs 46% (control) – mainly skin reactions

💬 Takeaway:
Perioperative EV + pembro markedly improves EFS, OS & pCR with manageable toxicity.
➡️ First regimen to outperform RC + PLND in cisplatin-ineligible MIBC — potential new SoC! 🏆

#ESMO25 #BladderCancer #OncoTwitter #Immunotherapy
@esmo_open @OncoAlert @myesmo @ASCO

[Dr Rishabh Jain @DrRishabhOnco]

🎯 HARMONi-6 delivers new hope in 1L advanced squamous #NSCLC 🫁

📍 Phase III | n=532 | 1L Stage IIIB–IV sqNSCLC
💊 Arms:
🔹 Ivonescimab + chemo (20 mg/kg Q3W)
🔹 Tislelizumab + chemo (200 mg Q3W)
→ Followed by monotherapy maintenance

📈 Results:
• PFS: 11.1 mo vs 6.9 mo (HR 0.60 [0.46–0.78], p<0.0001)
• PD-L1 < 1%: 9.9 vs 5.7 mo (HR 0.55)
• PD-L1 ≥ 1%: 12.6 vs 8.6 mo (HR 0.66)
✅ Consistent benefit across subgroups

⚕️ Safety:
• SAE 32.3 % vs 30.2 %
• Grade ≥3 hemorrhagic events 1.9 % vs 0.8 %

🧩 Takeaway:
Ivonescimab-chemo shows superior PFS vs tislelizumab-chemo - emerging as a potential new 1L standard for advanced sqNSCLC.

#OncoTwitter #MedTwitter #LungCancer #Immunotherapy #ESMO25 @OncoAlert @myesmo @esmo_open