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Cervical Cancer ASTRO 2022 - Coggle Diagram

- - - - LACC
        Radical Hyst vs MIS
        
        3y OS 99% vs 94% (RH better)
        
        ConCerv Trial
        Is there early stage pop that can get conization or simple hyst.
        
        early results: 5% LN+
        
        2Y LR 3.5%
        
        mF/U 36 mo
        
        maybe
        
        SLNBx
        best for tumors < 2cm
        
        99% SN, 97-100% NPV
        
        SENTICOL III (RCT)
        
        4Y similar DFS, less morbidity
        
        watch for
        
        SENTICOL III
        
        SentiX
        
        SLNMICC
    - - Intermediate Risk: Adj RT only
        
        Sedlis Trial, Rotman 2006
        (Intermediate risk) IB upfront Sx
        
        Needed
        
        LVSI
        
        stromal inv (depth strat)
        
        tumor size (strat)
        
        mostly SCC (75%)
        RCT: Obs :telescope: vs RT :radioactive_sign:
        
        PFS (HR 0.58)
        
        OS not different
        
        ACA failed more with obs :telescope:
        
        ACA improved more with RT
        
        Levinson, Gyn Oncol 2021
        Histology specific nomogram
        NRG hypothesis generating ancillary study
        
        3 studies analyzed
        
        GOG 49, Delgado 1990: Prospective analysis
        
        Stage I cancer, SCC, DOI > 3mm
        
        Size >3cm, DOI, LVSI predict DFS
        
        GOG 92: Sedlis
        
        Size >4cm, deep 1/3 DOI, LVSI influence PFS and LR
        
        GOG 14, Eddy 2007
        
        Stage IB bulky cancer
        
        Surgery vs NAC w/ Surgery
        
        Death RR (0.98)
        
        Recurrence RR (1.008)
        
        Stage 1
        SCC : ACA (7:1)
        3Y recurrence factors
        SCC
        
        DOI
        
        size :baseball:
        
        LSVI :potable_water:
        
        ACA
        
        size ≥ 4 cm :baseball:
        
        LVSI :potable_water:
        
        Showed for those who meet Sedlis crit, the 3Y recurrence risk is variable
      - High Risk: CRT
        
        Peters Trial, JCO 2020
        IA2, IB, IIA upfront Sx
        
        Needed
        
        margin + :cookie:
        
        parametria + :tada:
        
        pelvic LN + :izakaya_lantern:
        
        Mostly SCC (80%)
        PA included if Com iliac + to 45 Gy
        RCT: Pelvic RT (49.3 Gy) vs. P. RT w/ CHT (Cis/5FU x 4 cycles/adjuvant)
        
        adj CHT is not typically given in modern era
        
        4Y PFS 63% vs 80% (CRT)
        
        4Y OS 71% vs 81% (CRT)
        
        ACA had worse outcomes
        
        ACA had best response (though not sig diff in multivar anal)
      - Postop Future directions
        
        Chemo Sequencing
        
        STARS trial
        IB-IIA
        Sedlis or Peters (adverse path)
        
        CRT vs CRT (Cis weekly) vs Sequential CRT (2x cycles carbo/taxol before and 2 after RT)
        Improved 3Y DFS and cancer death with Sequential CRT.
        probs w/ trial
        Concurrent is SOC
        
        GOG 263, Huang JAMA Onc 2021
        
        not released at time of rec
        
        Intermediate RF
        RCT: RT vs CRT
        
        Chemo intensification
        
        NRG 0724
        
        High RF
        RCT: CRT vs CRT w/ 4x cycles carbo/taxol
      - RT technique
        2 studies show IMRT > 3D
        
        RTOG 1203 TIME-C (RCT)
        
        postop Cervix or Endo
        
        45-50 w/ w/o brachy boost (6Gy x 2)
        
        25% got CHT
        
        1* endpoint EPIC bowel
        
        change in bowel reported worse in 3D
        
        n = ~300
        
        PARCER (RCT)
        Postop Cervix
        Pelvis only 50 Gy w/ brachy boost (6Gy x 2)
        CHT ~25%
        3y ≥ G2 late GI
        21% vs 42%
        DFS no diff.
        
        n = ~300
        
        PARCER (update) patterns of failure, Mittal 2022, Small 2021
        
        old vs new guidelines
        
        8% pelvic relapses
        
        9/19 relapses by old guidelines
        
        12/19 relapses by new guidelines
        
        PARCER guidelines covered more anterior (post bladder) and vesicovaginal space
        
        Updated NRG postop contouring atlas
        Small W IJROBP 2021
        
        CI LN go ant/post
        
        EI LN stop at deep circumflex
        
        Ob LN stop at Ob Notch
        
        PS 1-1.5 cm ant to sacrum
        
        Postop brachy boost
        
        ASTRO Cervix Consensus
        Brachy boost conditionally recommended if + margin (low quality evidence)
        NCCN doses (no true std)
        
        5.5 Gy x 2 @ 5mm
        
        6 Gy x 3 dosed at surf.
        
        data is mostly large studies
        
        NCBD showed ~7% improvement in 3Y OS w/ brachy boost.
- - - - Cochrane MA, Vale 2010
        
        Why CRT > RT
        
        6% improvement in 5y OS CRT vs RT (HR 0.81, p<0.001)
      - RTOG 9001, Eifel 2004
        
        LA Cervical Ca rand to CRT vs EFRT
        
        Rx to pt A
        
        brachy not image guided.
        
        OS 60-80%
        
        DFS 55-75%
        
        LRF 10-30%
        
        5y ≥ G3 toxicities 14%
      - Brachy advances: IGRT
        
        used dose points with flouro
        
        now use CT or MRI ensure tumor coverage
        
        Volume based IGABT, Haie-Meder, 2005
        MRI definitions
        
        White – Gross disease (GTV) Gross tumor at time of BT
        
        Yellow – High Risk CTV (HR-CTV) GTV+entire cervix+gray zones
        
        Orange – Intermediate Risk CTV (IR-CTV) HR-CTV+asymmetric expansion not extending into OARs, and including sites of initial disease involvement
        
        Gray zone: area of inv. that returns to normal after EBRT
        
        CT based contouring guidelines
        Mahantshetty U et al, 2021
        
        Point A vs Volume-based brachy – Meta-analysis, Hande V, 2022
        24 studies, 5488 pts
        Vol based vs Pt A based
        
        3Y LC 86% vs 92% (+6%)
        
        3Y DFS 67% vs 79% (+12%)
        
        3 Y OS: no diff
        
        Late GU/GI ≥3: no diff
        
        COMBAT Trial, ongoing
        RT w/ Pt A vs MRI
        
        EMBRACE Studies
        
        retroEMBRACE
        HR-CTV D90 ≥ 85 Gy in 7 weeks 3y LC:
        
        94% for HR-CTV 20 cm3
        
        93% for HR-CTV 30 cm3
        
        86% for HR-CTV 70 cm3
        
        Incr HR-CTV vol by 10 cm3 requires additional 5 Gy for equivalent local control
        
        more vol drops local control at a set dose
        
        Dose of 5 Gy to HR-CTV is required to overcome increase in Overall Treatment Time of 1 week
        
        The pattern of recurrence has shifted to Dist. Recurrence
        in MA comparing IGABT vs pt A sudies.
        
        pelvic only failures have decreased (~16% vs 6%)
        
        distant failures have increased (12% vs 17%)
        
        greater benefit of Intercav/Interstit w/ larger HR-CTV and safe to use needles
        
        Fokdal 2016
        `HR-CTV > 30cc had +10% LC if needles were used
        
        23% needles (IS) ≥1 fx
        
        Av D90 HR-CTV 9 Gy higher w IC/IS (83 vs 92 Gy)
        
        Similar OAR doses
        
        Similar toxicities
        
        Needles improve coverage and limit OAR dose
        
        asymmetry: can be a benefit
        
        asymmetric location of OARs.
        
        EMBRACE I
        prostpective
        
        > 1,000 pts
        
        43% IC/IS, OTT 46 d
        
        Median HR-CTV 28 cm3
        
        Median D90 90 Gy
        
        5y LC 92%
        
        5y DFS/OS 68%/74%
        
        5y cumulative incidence G3-5 tox:
        
        GU – 7%
        
        GI – 9%
        
        Vaginal – 6%
        
        Fistula – 3%
        
        OARs
        
        Spampinato 2022
        combined dose EBRT & BT, Rectum D2cc < 65 Gy
        
        greater bleeding and proctitis
        
        Bladder D2cc < 80 Gy
        
        more G2 fistulas, bleeding, cystitis
        
        ICRU Bladder Pt correlates
        
        to pain (keep < 70 Gy)
        
        to incontinence (more than bladder D2cc) (keep < 75 Gy)
        
        5y actuarial estimate ≥ G2 incontinence:
        
        20% > 75Gy
        
        11% ≤ 65Gy
        
        Ureter
        no agreed upon constraint, Fokdal, 2019
        
        5y risk G3-4 stricture:
        
        T1-2 ≤1%
        
        T3-4 without hydro at diagnosis 5%
        
        T3-4 with hydro at diagnosis 12%
        
        Retrospective U Pitt, Rodriguez-Lopez, 2020
        
        D0.1 cm3 ≤ 77 Gy correlates with late ≥ G3 ureteral stenosis
        
        Sexual function
        
        50% still sexually active after tx
        
        20% still find sex enjoyable
        
        Higher doses to Post Inf Border Symphysis +2, PIBS, RectoVag-Ref Pt associated with ≥ G2 vaginal stenosis
        
        keep RV-RP < 65 Gy
        
        also associated with higher risk
        
        Vaginal involvement at dx,
        
        shorter Vag Ref length,
        
        use of T+O
        
        In summary, use the EMBRACE II protocol: D90 > 85 Gy
        
        also look at NCCN and ASTRO cervix practice guidelines
        
        Duodenal dose constraint
        Need to think about changes in target and bowel especially with SIB approaches
        
        Duodenal dose V55 <15 cm3 and V60 < 2 cm3
        
        Duo Tox: 3y 49% vs 7%
        
        Median V55 3.5 cm3 (IQR 0.2-8.1 cm3)
        
        Median V60 0.3 cm3 (IQR 0.0-1.8 cm3)
        
        4 more items...
    - - Outback CHT doesnt improve OS, PFS
        
        Horeweg N et al. Critical reviews in Oncol Hematol. 2022.
        
        IO in definitive setting
        
        NRG GY017
        
        ATEZOLACC
        
        CALLA
        
        ATOMICC
        
        KETNOTE A18
        
        KEYNOTE 826
        Persistent, recurrent, metastatic cervical CA
        Colombo N et al. NEJM. 2021.
        Chemo +/- bev + Pembro vs. CHT +/- bev
        
        PD-1-blocking Ab
        
        Need to be PDL1+
        
        2y OS 50% vs 40%
        
        CR rate ~20%
        
        EMPOWER Cervical 1/ GOG- 3016/ENGOT-cx9
        Tewari K et al. NEJM. 2022.
        Disease Progression after 1st line platinum chemo
        
        Cemiplimab PD-1-blocking Ab vs. single agent CHT
        
        Any PDL1 status
        
        Median OS 12.0 vs 8.5 m, p<0.001