onc brain

About · curated by Nick Boehling, MD · @nb2276

    2026-07-31

    digest generated 2026-09-26

    POSEIDON: adding HT to PORT missed OS across 6 RCTs (HR 0.87, p=0.06); OS benefit confined to pre-PORT PSA >0.5 ng/mL (HR 0.72 at 0.51-1.00, 0.69 >1.00).
    TL;DR
    Prostate carried the day. POSEIDON limits HT with PORT to pre-PORT PSA >0.5. GÖTEBORG-1 shows 25-yr PCSS 94% on AS, but only 38% of men were still treatment-free at 22 yr. The RT dose and planning signals are hypothesis-generating: retrospective SIB escalation in MIBC TMT, and a preprint randomized phase II of immune-sparing lung SBRT.

    Kidney

    First international IROCK consensus on iGTV delineation for localized RCC SABR.

    Consensus

    IROCK RCC SABR contouring guidelines

    ForLocalized RCC treated with SABR, incl. IVC thrombus, recurrence, post-RFA

    TL;DRFirst international consensus on target delineation for localized RCC SABR: 16 experts, median DSC 0.85 vs consensus, >0.70 in every case.

    Why it mattersRadiation oncology

    The two contested target calls are settled: include the entire tumor thrombus and the entire RFA cavity, and these were also the cases with most variation (DSC 0.85 and 0.75; HD 64.60 mm in Case 1). The 5 mm PTV assumes 4DCT, vacuum cushion, IV contrast and daily CBCT, so a center without those shouldn't copy the margin.

    Monday clinic

    In a medically inoperable localized RCC with IVC tumor thrombus or recurrence after RFA, this supports covering the full thrombus or full ablation cavity in the iGTV; it does not settle the dose or fraction number, which the panel left institution-specific. The longer read

    10 details
    Design

    Contouring consensus: 16 IROCK radiation oncologists contoured 4 CT-only cases; a STAPLE algorithm produced the 95% consensus contour, refined over 2 online meetings (May and June 2024) until 100% agreement on statements.

    Population & inclusion

    Panel eligibility: ≥10 RCC SABR cases treated; 14 of 16 had treated ≥10 pts in the prior 12 months. Cases: >10 cm tumor with IVC thrombus, central tumor at the hilum, post-nephrectomy recurrence, post-RFA residual.

    Radiotherapy

    iGTV equals ITV since no microscopic-spread margin is added. Most common PTV: uniform 5 mm on iGTV with supine vacuum cushion, 4DCT, IV contrast and daily CBCT. Participants used 1, 3, or 5 fractions; OAR constraints drawn from FASTRACK-II and AQuOS-II protocols.

    Results

    Overall median DSC 0.85 (range 0.40-0.95), MDA 2.17 mm, HD 9.00 mm; median DSC >0.70 in every case. Greatest variation in Case 1 (superior thrombus extent) and Case 4 (cavity inclusion).

    CaseScenarioiGTV recommendation
    1Tumor >10 cm with IVC tumor thrombusPrimary tumor + entire tumor thrombus; exclude bland thrombus
    2Central tumor abutting renal hilumAll visible tumor, account for internal motion; may extend into hilum
    3Local recurrence post-nephrectomyAll visible gross tumor; surgical clips need not be included
    4Residual tumor post-RFAVisible gross recurrence + entire ablation cavity
    CaseDSCMDA (mm)HD (mm)
    10.85, 0.79-0.856.69, 5.88-8.7964.60, 64.44-86.40
    20.90, 0.84-0.931.55, 1.00-2.097.92, 5.35-9.98
    30.91, 0.88-0.931.42, 1.18-1.896.18, 6.00-7.12
    40.75, 0.60-0.792.50, 2.12-2.999.00, 9.00-12.39
    vs leading data

    FASTRACK-II established prospective phase II support for RCC SABR; this document standardizes the target and OAR definitions that trial-era protocols left variable. AQuOS-II is prospectively testing whether ipsilateral parenchyma and hilum contours matter for toxicity.

    Applies to
    localized RCC treated with SABR in centers with 4DCT, contrast and CBCT
    Does not represent MRI-guided or adaptive workflows, where the 5 mm margin may differ.
    Limitations

    CT-only images; MRI might have reduced variation. Participants did not recontour after consensus, so the post-consensus agreement is assumed rather than measured.

    Discussion

    The guideline chooses OAR priority over coverage and accepts heterogeneous target dose, which trades some target coverage for bowel safety. Whether hilum or cortex sparing reduces renal toxicity remains unanswered and is deliberately left optional.

    Rationale

    Expert contouring consensus; agreement metrics measure contour overlap, not outcome. Standardizes target definition for an emerging indication; not validated prospectively.

    Open questions
    • Does renal hilum or cortex sparing reduce renal toxicity?
    • Patterns of failure with the 5 mm PTV margin
    • Does MRI-based contouring reduce target variation?

    Sourced from Dhar, Aneesh et al.

    📚 Sources · 📄 1 paper
    📄 PAPER Dhar, Aneesh; Siva, Shankar; Tan, Vivian S. et al. · International Journal of Radiation Oncology*Biology*Physics (2026-05)
    International Radiosurgery Oncology Consortium of the Kidney (IROCK) Contouring Guidelines for Renal Cell Carcinoma Treated With Stereotactic Ablative Radiation Therapy
    doi

    Radiation Curative Consensus / guideline Consensus

    Prostate

    Two long-horizon datasets: which men get HT with salvage RT, gated by pre-PORT PSA, and 25-yr AS outcomes from the pre-MRI era.

    Caveats dominate

    GÖTEBORG-1 active surveillance, 25-year follow-up

    ForScreen-detected very-low/low/intermediate-risk localized PC on AS

    TL;DR25-yr PC-specific survival 94% (CI 91-98%) on AS, but 22-yr failure-free survival 68% and treatment-free survival 38%.

    Why it mattersRadiation oncology

    RT was the exit for 44 of 488 men, but the paper reports no outcomes by treatment, so the efficacy of delayed RT after AS can't be separated out. Failure kept accruing past 10 yr in every risk group. For a man choosing AS over upfront RT, the trade is decades of monitoring, not a 10-15 yr window.

    Monday clinic

    In a screen-detected very-low or low-risk man, this supports AS as low risk for PC death out to 25 yr. In intermediate-risk disease (24-yr PCSS 85%, 19-yr FFS 55%), it supports discussing upfront definitive therapy as a real alternative. It does not extend to high-risk PC. The longer read

    12 details
    Design

    Observational AS cohort inside the GÖTEBORG-1 PSA screening trial (1995 to 2014 diagnoses, follow-up to Dec 31, 2023). Data were collected prospectively, but AS was not randomized and followed no predefined protocol. Kaplan-Meier estimates plus a multivariable Cox model for failure.

    Population & inclusion

    Of 1052 screen-detected PCs, 494 (47%) were on AS and 488 were included: 251 very-low, 129 low, 108 intermediate risk. High-risk excluded. Median age 66, PSA 4.1 ng/ml, PSA density 0.12.

    Endpoints

    Treatment-free, failure-free (noncurative PSA relapse, starting HT, metastasis, or PC death), PC-specific, and overall survival, all measured from diagnosis.

    Radiotherapy

    RT was the active treatment for 44 men leaving AS, against 141 RP. Post-RT relapse was defined as nadir +2 ng/ml. No dose, technique, or RT-specific outcome is reported.

    Results

    PCSS 94% at 25 yr against FFS 68% at 22 yr; 14 PC deaths and 81 failures. Gleason score (HR 3.12) and PSA density (HR 1.78) predicted failure.

    Endpoint15 yr20 yr22 yr25 yr
    PC-specific survival97% (CI 95-99%)95% (CI 93-98%)n/a94% (CI 91-98%)
    Overall survival63% (CI 58-67%)46% (CI 41-51%)n/a32% (CI 26-38%)
    Treatment-free survival48% (CI 43-54%)43% (CI 37-50%)38% (CI 31-46%)n/a
    Failure-free survival81% (CI 77-85%)74% (CI 68-81%)68% (CI 60-78%)n/a
    EndpointVery low (n=251)Low (n=129)Intermediate (n=108)
    TFS 19 yr55% (CI 48-63)35% (CI 26-47)30% (CI 18-48)
    FFS 19 yr85%74%55%
    PCSS 24 yr99% (CI 97-100)92% (CI 83-100)85% (CI 75-95)
    OS 24 yr38% (CI 30-48)34% (CI 26-45)22% (CI 12-37)
    vs leading data

    PC mortality falls in the range of ProtecT (3.4%) and the Toronto cohort (5.7% at 15 yr). It is roughly half of PIVOT (11.4%) and well below SPCG-4, a gap the authors attribute to screen detection versus clinical diagnosis.

    Applies to
    screen-detected very-low, low, and intermediate-risk localized PC followed with PSA and sextant-era biopsies
    Does not represent high-risk PC or MRI-selected, MRI-monitored contemporary AS cohorts.
    Limitations

    Gleason reclassification after 2005 means some low-risk pts here would be intermediate risk today. Failure lumps PC death with untreated low-level PSA relapse. Risk-group differences in PCSS were not formally tested.

    Discussion

    Failure hazard stayed roughly constant over time, and nearly half of failures came >10 yr after diagnosis, so there is no safe point to stop monitoring. Failures in Gleason 6 pts show that some Gleason 6 tumors do progress.

    Rationale

    Nonrandomized AS cohort with no comparator arm and no predefined surveillance protocol. Pre-MRI sextant selection limits how far the result transfers to contemporary AS.

    Open questions
    • Does MRI-based selection and monitoring lower long-term AS failure?
    • Is there any safe point to stop AS monitoring?
    • How does intermediate-risk AS perform under modern grading?

    Sourced from Palmstedt, Emmeli et al.

    📚 Sources · 📄 1 paper
    📄 PAPER Palmstedt, Emmeli; Månsson, Marianne; Hugosson, Jonas et al. · European Urology (2025-10)
    Active Surveillance for Screen-detected Low- and Intermediate-risk Prostate Cancer: Extended Follow-up up to 25 Years in the GÖTEBORG-1 Trial
    doi

    Curative Caveats dominate

    Challenges SOC

    POSEIDON

    ForPost-RP prostate cancer receiving PORT, median pre-PORT PSA 0.3 ng/mL

    Overall survival

    HR 0.87

    95% CI 0.76–1.01, p=0.06; not met

    TL;DRIPD meta-analysis of 6 RCTs: adding HT to PORT did not improve OS (HR 0.87, 95% CI 0.76–1.01, p=0.06); benefit confined to pre-PORT PSA >0.5 ng/mL.

    Why it mattersRadiation oncology

    MFS improved (HR 0.79) but never cleared the ICECaP 0.81 surrogate threshold at any pre-PORT PSA, so the bPFS/MFS gains behind GETUG-AFU 16 and RTOG 0534 were not expected to translate to OS. Duration showed no interaction (p=0.17); long-term HT OS benefit on splines appears only at PSA ≥1.6 ng/mL, above most modern early salvage.

    Monday clinic

    In PET-negative BCR after RP heading to early salvage PORT at PSA ≤0.5 ng/mL, this questions adding HT for survival; above 0.5 ng/mL it supports HT, with no OS evidence favoring 24 over 4–6 mo; it does not extend to PSMA PET-positive nodal disease. The longer read

    14 details 5 trials watching
    Design

    IPD meta-analysis of six randomised phase 3 trials via the MARCAP consortium (PROSPERO CRD42019134376), one-stage Cox stratified by trial. 6057 pts, median follow-up 9.0y (IQR 7.2–10.7).

    Population & inclusion

    Men receiving PORT after radical prostatectomy for recurrent prostate cancer. Median pre-PORT PSA 0.3 ng/mL in the any-HT and short-term sets, 0.5 ng/mL in the long-term set. Race and ethnicity data not available.

    Regimen

    Short-term HT 4–6 mo (GETUG-AFU 16, NRG/RTOG 0534, RADICALS-HD two-way and three-way), predominantly GnRH agonist. Long-term HT 24 mo (RADICALS three-way, RTOG 9601); RTOG 9601 used high-dose bicalutamide monotherapy.

    Endpoints

    Primary: overall survival. Secondary: MFS, event-free survival, biochemical recurrence; prespecified interaction tests for pre-PORT PSA and HT duration.

    Results

    No OS benefit overall (HR 0.87, p=0.06) despite MFS gain (HR 0.79, p<0.001). OS benefit limited to pre-PORT PSA >0.5 ng/mL (interaction p=0.02), with NNT 22 at 0.51–1.00 and 12 at >1.00 ng/mL.

    ComparisonNOS HR (95% CI)MFS HR (95% CI)
    Any HT + PORT vs PORT50260.87 (0.76–1.01), p=0.060.79 (0.70–0.89), p<0.001
    Short-term HT (4–6 mo)39380.93 (0.77–1.11)0.82 (0.71–0.95)
    Long-term HT (24 mo)10880.79 (0.63–1.00), p=0.0490.74 (0.60–0.91), p=0.004
    Short → long prolongation15230.89 (0.68–1.16), p=0.370.76 (0.61–0.95), p=0.02
    Pre-PORT PSA (ng/mL)OS HR (95% CI)10y OS PORT vs PORT+HT10y NNT (death)
    ≤0.201.14 (0.83–1.57)89.9% vs 87.4%negative
    0.21–0.500.94 (0.74–1.19)84.9% vs 84.5%negative
    0.51–1.000.72 (0.54–0.96)76.4% vs 80.9%22
    >1.000.69 (0.48–0.98)72.4% vs 80.5%12
    vs leading data

    GETUG-AFU 16 and RTOG 0534 established HT with salvage RT on biochemical endpoints; per the ASCO Post write-up only RTOG 9601, a late-salvage trial, had shown an OS benefit. POSEIDON pools these trials and finds the OS signal tracks pre-PORT PSA rather than HT duration.

    Applies to
    PET-negative biochemical recurrence after RP treated with PORT, mostly early salvage
    Does not represent PSMA PET-positive nodal or metastatic disease, or biomarker-selected (Decipher) decisions.
    Limitations

    Duration comparison is confounded: long-term HT trials enrolled higher-PSA, higher-risk pathology. The PSA interaction is model-dependent (continuous PSA: one-stage p=0.19, two-stage p=0.04) and no multiplicity correction was applied. RT dose and field detail not reported in source excerpt.

    Discussion

    The trial-level MFS gains held but did not clear the ICECaP surrogate threshold, so the historical case for routine HT with low-PSA salvage rests on endpoints that do not predict OS here. Short-term HT may suffice where HT is used; NRG GU006 (PAM50, apalutamide) tests biomarker selection.

    Rationale

    Pooled randomised IPD with prespecified OS primary not met, undercutting routine HT with low-PSA PORT. The PSA >0.5 benefit rests on subgroup interaction, not a primary comparison.

    Open questions

    Sourced from Kishan, Amar U et al.

    📚 Sources · 📄 2 papers
    📄 PAPER Kishan, Amar U; Sun, Yilun; Parker, Christopher C et al. · The Lancet (2026-03)
    Hormone therapy use and duration with postoperative radiotherapy for recurrent prostate cancer: an individual patient data meta-analysis
    doi
    📄 PAPER · The ASCO Post
    For Most Men With Prostate Cancer, Hormone Therapy With Postprostatectomy Radiotherapy Confers No Survival Benefit
    article →
    Abstract
    Adding hormone therapy to postprostatectomy radiotherapy may provide little survival benefit for most men with prostate cancer, especially those with very low prostate-specific antigen (PSA) levels be...
    📝 https://ascopost.com/issues/march-25-2026/for-most-men-with-prostate-cancer-hormone-therapy-with-postprostatectomy-radiotherapy-confers-no-survival-benefit/

    Combined Curative Meta-analysis Challenges SOC

    Bladder

    Caveats dominate

    Dose-escalated RT for MIBC (retrospective)

    ForMIBC T2-3, M0 (node+ allowed), post-TURBT curative RT ± concurrent chemo

    TL;DR2y invasive local recurrence 5.5% vs 27.5% with SIB dose escalation in MIBC TMT (adjusted SHR 0.20, p=0.035); no OS, MFS or G2+ toxicity difference.

    Why it mattersRadiation oncology

    Pattern of failure is the RT read: standard-dose invasive failures sat at the original tumour site (14 within vs 2 outside), and the escalated cohort had 1 invasive failure inside the boost. A 60Gy/20fx or 70Gy/32fx SIB to the primary on daily CBCT carried no G2+ GU/GI cost, which supports testing primary-tumour escalation in TMT.

    Monday clinic

    In a unifocal MIBC TMT candidate without hydronephrosis, this supports a primary-tumour SIB as a trial-worthy option rather than routine practice; it does not extend to multifocal disease, which the escalated cohort never included. The longer read

    12 details 1 trial watching
    Design

    Multicentre retrospective cohort from 3 centres, March 2015 to May 2025. N=107: 39 dose-escalated vs 68 standard. Median follow-up 23 mo (range 3-104).

    Population & inclusion

    Curative-intent MIBC after TURBT, RT with or without concurrent chemo; node-positive allowed if M0. Metastatic or palliative-intent pts excluded. 51% received no chemo, mostly for poor PS or comorbidity.

    Radiotherapy

    Standard: 55Gy/20fx or 64Gy/32fx whole bladder. Escalation: SIB up to 60Gy/20fx or 70Gy/32fx to the primary lesion. Empty-bladder CT sim, daily CBCT, MRI/FDG PET fusion in select pts.

    Endpoints

    2-year local control for invasive and non-invasive disease, metastasis-free survival, OS, bladder preservation and toxicity. Invasive recurrence analysed by Fine-Gray competing-risk models.

    Results

    Invasive recurrence was the only endpoint that separated (adjusted SHR 0.20, p=0.035); non-invasive recurrence, metastasis and OS did not differ. Full arm values in the table.

    EndpointEscalated (n=39)Standard (n=68)Effect
    2y invasive local recurrence5.5%27.5%SHR 0.20 (0.05-0.89), p=0.035 (MVA, T stage)
    2y non-invasive recurrence6.7%9.9%SHR 0.88 (0.23-3.33); MVA p=0.79
    2y metastasis21.1%32.3%MVA p=0.75
    2y OS71.1%64.4%p=0.5
    G2+ GU toxicity17.9%22.1%p=0.8
    G2+ GI toxicity5.1%7.4%p=0.9
    Cohort / siteInvasiveNon-invasive
    Escalated, within boost field10
    Escalated, outside boost field13
    Standard, within original tumour site142
    Standard, outside original tumour site25
    Safety

    G2+ GU 17.9% vs 22.1% and G2+ GI 5.1% vs 7.4% (escalated vs standard), no difference (p=0.8, p=0.9). G3 toxicity only in 2 standard-dose pts; no early cessation.

    vs leading data

    BC2001 and BCON built modern TMT on radiosensitisation of whole-bladder RT, not on dose to the primary. RAIDER tested tumour-focused adaptive escalation prospectively; this series adds a routine-practice, CBCT-era hypofractionated experience in the same direction.

    Applies to
    unifocal, predominantly T2, M0 MIBC treated with curative hypofractionated TMT under daily CBCT
    Does not represent multifocal disease, metastatic or palliative-intent pts.
    Limitations

    Asymmetric outcome ascertainment: 3 standard-arm recurrences were imaging-only and presumed invasive, while every escalated recurrence was cystoscopy-confirmed. Chemo use (56% vs 44%) and hypofractionation (97% vs 87%) also favoured the escalated cohort, and f/u starts at 3 mo, short for late bladder toxicity.

    Discussion

    The in-field failure pattern in the standard cohort gives escalation a mechanistic rationale; the magnitude is not trustworthy given selection. Bladder preservation was high in both groups partly because relapsed pts were unfit for cystectomy, so it conflates control with fitness.

    Rationale

    Retrospective, non-randomised; escalated cohort selected (all unifocal, less hydronephrosis). Few invasive events (2 vs 16), adjusted for T stage only, so dose cannot be separated from selection.

    Open questions

    Sourced from Chan, Li et al.

    📚 Sources · 📄 1 paper
    📄 PAPER Chan, Li; Anzela, Anzela; Do, Viet et al. · Advances in Radiation Oncology (2026-07)
    Dose-Escalated Radiotherapy for Muscle Invasive Bladder Cancer: A retrospective analysis
    doi

    Radiation Curative Retrospective Caveats dominate

    Thoracic / Lung

    Early signal

    Proactive immune cell sparing SBRT (NCT04273893) NCT04273893

    PREPRINTnot peer-reviewed

    ForEarly-stage NSCLC, inoperable or declining surgery, SBRT without systemic therapy

    Overall all-timepoint ALC reduction improvement surrogate

    13.4% (5.3%)

    95% CI 2.8 to 24.0; p = 0.01

    TL;DRImmune-sparing lung SBRT planning cut ALC loss: overall improvement 13.4% (95% CI 2.8-24.0), G3 lymphopenia 0% vs 15.4%; survival trend unpowered.

    Why it mattersRadiation oncology

    The dosimetric lever is low-dose spill, not the target: V5 to thoracic spine fell 87% and LN stations 58% with lung V5 down only 8%, all within RTOG 0813/0915 criteria. Benefit concentrated in central tumors (29.5% ALC gain) and was absent for peripheral PTV <20cc, so arc and beam-angle choices for central SBRT are where this plan change applies.

    Monday clinic

    In a central early-stage NSCLC going to 5-fx SBRT without systemic therapy, this supports treating heart, great vessels, thoracic spine and LN stations as low-dose avoidance structures; it does not change planning for small peripheral PTVs under 20cc or establish a survival gain. The longer read

    16 details
    Design

    Randomized phase II, 1:1, stratified by tumor location, permuted blocks, not masked. Enrolled Feb 2020 to Apr 2023; 55 randomized, 51 analyzed (25 vs 26). Survival and subgroup analyses were unplanned and exploratory.

    Population & inclusion

    Early-stage NSCLC (AJCC v8), ECOG 0-2, unable or unwilling to undergo surgery; recurrent NSCLC eligible. Excluded RT within 2 yr and systemic therapy within 1 yr prior or 6 mo after. Median age 74 both arms.

    Radiotherapy

    45-60 Gy in 5 fx (majority 60 Gy/5), IMRT or VMAT, 4DCT ITV plus 5mm radial / 8mm sup-inf PTV margin. Optimized plans met standard RTOG 0813/0915 criteria while minimizing dose to heart, great vessels, thoracic spine and lymph-node-stations, contoured to a 40 cGy/fx low-dose envelope.

    Endpoints

    Primary: in vivo lymphocyte depletion at end of treatment, 4 wk and 6 mo; safety/toxicity (co-primary). Algorithm performance reported separately. OS and EFS descriptive only.

    Results

    Central tumors drove the effect (29.5% overall ALC improvement, p=0.004); peripheral PTV <20cc showed no difference. G3 lymphopenia 0% vs 15.4% (p=0.04).

    TimepointOptimizedStandardBetween-group diff
    End of SBRT-16%-31%15.1% (3.7-26.5), p=0.01
    4 weeks-22%-34%12.3% (0.2-24.5), p=0.05
    6 months-16%-26%10.4% (-4.7-25.5), p=0.17
    Population · endpointOptimizedStandardp
    All pts · OS82.1%65.1%0.23
    All pts · EFS62.3%56.7%0.27
    Tx-naive · OS93.4%69.4%0.14
    Tx-naive · EFS75.0%59.8%0.10
    Safety

    G3 AEs 2 (lung infection) optimized vs 4 standard (dyspnea, hypoxia, lung infection); all recovered. No G2+ pneumonitis or G4+ events in either arm.

    vs leading data

    Both arms sat inside RTOG 0813/0915 planning criteria, so the comparison isolates immune-OAR avoidance on top of current SBRT constraints. Prior lymphopenia-outcome links in thoracic RT are largely associative; this is a randomized test that planning alone moves ALC.

    Applies to
    inoperable early-stage NSCLC treated with 5-fx SBRT alone, especially central tumors
    Does not represent SBRT combined with immunotherapy or chemotherapy, conventionally fractionated chemoRT, or small peripheral PTVs under 20cc.
    Limitations

    Arm imbalance in central (36.0% vs 23.1%) and treatment-naive (64.0% vs 88.5%) pts biases the survival comparison. Tx-naive OS reported as 93.4% and 94.1% in different sections. LN V5 OS split is a non-randomized dosimetric stratification.

    Discussion

    Establishes feasibility and an ALC effect, not a clinical one. Whether sparing lymphocytes during SBRT translates to EFS/OS, or to better IO response when combined, needs the multi-institutional powered trial the authors call for.

    Rationale

    Preprint, small randomized phase II with unmasked lymphocyte surrogate primary; survival analyses unplanned and unpowered. Arm imbalance in central and treatment-naive pts.

    Open questions
    • Does lymphocyte-sparing SBRT improve EFS or OS in a powered trial?
    • Does immune-sparing planning enhance SBRT plus immunotherapy outcomes?
    • Optimal dose limits for thoracic spine and lymph-node-stations

    Sourced from Wijesooriya, Krishni et al.

    📚 Sources · 📄 1 paper
    📄 PAPER Wijesooriya, Krishni; Nguyen, Cam; Conaway, Mark R et al. · medRxiv (2025-01)
    First Measurement: Proactive Immune Cell Sparing in Radiation Therapy
    PMID 16111586 → doi
    Abstract
    Abstract Purpose Radiation Therapy (RT) can modulate the immune system and generate anti-tumor T cells. However, this anti-tumor-activity is countered by radiation-induced immunosuppression (RIIS). Clinical advantages of proactively sparing RT dose to immune rich organs have not previously been evaluated. Methods We conducted a phase II randomized trial from 2020 to 2023, enrolling 51 early-stage lung cancer patients treated with SBRT, to evaluate the effect of dose reduction to immune rich organs on RIIS. Two groups were: RIIS-optimized-treatment (lowering the dose to blood, bone-marrow and lymph-node-stations) and standard-treatment. All treatments followed national protocol guidelines. Peripheral blood was collected at baseline, immediately, 4-weeks and 6-months post-treatment. Results ALC changes from baseline immediately, 4-weeks and 6-months post-SBRT are: optimized-arm: -16%, -22%, -16%, standard-arm: -31%, -34%, -26%, leading to an overall-all-time-point improvement in ALC reduction in the optimized-arm compared to the standard-arm of 13.4 (5.3) % (95% CI, 2.8 to 24.0; p = 0.01). Central tumors had the largest improvement in ALC from baseline: optimized-arm: - 8%, -18%, -14%, standard-arm: -39%, -43%, -47%, leading to an overall-all-time-point improvement in ALC reduction in the optimized-arm compared to the standard-arm of 29.5 (9.6) % (95% CI, 10.1 to 48.9; p = 0.004). Grade 3 lymphopenia occurred in 15.4% of standard arm patients but was absent in the optimized arm. Additionally, 2.8 times more patients in the optimized arm experienced an ALC increase post-SBRT. Dose to organs such as the heart, great vessels, thoracic spine, and lymph nodes significantly correlated with RIIS. A trend towards increased Event-Free-Survival (two-year: 75.0% (SE = 10.8%) versus 59.8% (SE = 11.2%), p =0·10) and Overall Survival (two-year: 93.4% (SE=6.1%) versus 69.4% (SE=10.5%), p =0·14) was observed with optimized-planning compared to standard-planning in treatment naïve patients. Conclusion Reducing RT dose to immune rich organs significantly reduces RIIS compared to standard-of-care. This has implications in enhancing immune system mediated anti-tumor-activity. (Funded by National Cancer Institute and others. ClinicalTrials.gov number, NCT04273893 )

    Radiation Curative Phase 2 trial Early signal