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Head and Neck ASTRO Refresher 2022 - Coggle Diagram

- - - - Intergroup Adelstein, JCO, 2003: Where Cisplatin :pill: comes from
        
        randomized Stage III&IV OPX, HPX, OC, Lx
        N=295
        
        RT: 70 Gy
        
        :trophy:ChemoRT: 70 Gy w/ CDDP 100mg/m2 in 1,4,7 week
        
        ~~Split course chemo RT: 30-40 Gy + CDDP 75mg/m2 and 5FU 1g/m2 x 4 days Q3wk~~ (ignore)
        
        OS ChemoRT: 3y 37%
        OS RT: 3y 23%
        :biohazard_sign: Acute Toxicity
        OS ChemoRT: 3y 89%
        OS RT: 3y 52%
        
        GORTEC: Carbo/5FU also works
        
        n=266
        86% T3-T4
        
        RT: 70 Gy in 35 fx
        
        chemoRT: 70/35 + CHT
        
        carbo 70mg/m2 x4
        
        5 FU 600 mg/m2 x4 on day 1,22,43
        
        OS ChemoRT: 5y 22%
        OS RT: 5y 16%
        :biohazard_sign: Late Toxicity
        ChemoRT: 5y 56%
        RT: 5y 30%
        
        MACH-NC: Metaanalysis for concurrent chemo: single agent CRT is the best
        
        n = 19805
        H&N SCC trials comparing local treatment with chemo or without
        Meta-analysis of 107 randomized trials
        concurrent chemo 5-yr OS benefit of +6.5%.
        Concurrent chemo improves LRF
        Induction and adjuvant improve DM
        Efficacy decreases with increasing age and performance status
        No OS improvement with induction chemo
        Meta-analysis confirms an OS benefit with the addition of concurrent chemotherapy to RT in H&N tumors. There is no benefit with induction chemotherapy.
        
        NRG-HN009 ongoing trial
        
        P16+/-
        
        weekly CDDP vs high dose CDDP
        
        can weekly be proven adequate in definitive chemoRT setting?
      - Alternative CHT?
        
        Carboplatin/paclitaxel
        The data is conflicting on benefit vs. Cetuxumab
        not a realistic alternative
        
        2 studies
        
        Xiang et al
        
        Karivedu et al
        
        Cetuxumab :elephant:
        
        IMCL Phase III :elephant:
        
        Dealers Choice RT +/- Cetuximab
        
        Stage III / IV
        
        definitive Tx, no postop patients
        
        RT only
        
        RT & Cetuximab :elephant:
        RT conventional 70 Gy, or hyperfrac 72-76.8 Gy/ 1.2 BID, or CCB 72 Gy/ 42 fx
        
        most pts have AFx
        were randomized w/ or w/o Cetuximab
        LRC better in cetixumab arm
        Median LC 24 vs. 15 mos
        2-yr LC 50% vs 41%
        median OS 49 vs. 29 mos
        3-yr OS 55% vs 45%. Acneiform rash and infusion reactions more common, but otherwise not more toxic.
        OS for grade 2-4 acneiform rash 69 mos vs 25 without
        Favorable factors on analysis: oropharynx, EGFR >50%, hyperfx, CCB, node positive, age <65
        
        Deintensification studies
        focus on p16+ OPX
        
        excellent outcomes in the past
        
        high sensitivity to CHT and RT
        
        focus on minimal smoking hx
        
        nonbulky primary and nonextensive pattern of disease spread
        
        RTOG 0129 Phase III trial : Concomitant CRT with standard vs Accelerated fractionation RT in advanced SCCHN
        
        in combo w/ CDDP
        
        no positive primary endpoint
        
        analysis showed p16+ OPX cancers into a low risk (for death) category.
        
        HPV positive vs. negative has different prognosis.
        3-yr OS by RPA group (see commentary for classes):
        Low risk: 93%
        Int risk: 71%
        High risk: 46%
        3-yr OS HPV+/HPV-: 82% vs. 57%
        3-yr DM HPV+/HPV-: 9% vs. 15%
        3-yr LRC HPV+/HPV-: 86% vs. 65%
        "Good risk" HPV+ (T1-2N1-2b or T3N0-N2b, and ≤10 py):
        8-yr LRF 86%, OS 81%, DM 8.3%
        For RT regimens, No difference in 8-yr OS, PFS, LRF, DM, or toxicity
        
        RTOG 1016 randomized ph3: Cetux is inferior
        
        1st head to head with Cisplatin vs. Cetuximab :elephant:
        
        for chemoRT
        
        p16+ as surrogate for HPV
        
        toxicity events considerable for Cetuximab :elephant: and CDDP
        
        included all risk patients
        
        HPV+ locally advanced oropharynx p16+. T1-2 N2a-3 or T3-4, any N
        →RT 70 Gy in 6 weeks (DAHANCA) SIB 56 & 52.5 Gy with concurrent cisplatin
        vs.
        →cetuximab
        5-yr OS 85% vs. 78%
        5-yr PFS 78% vs. 67%
        5-yr LRF 10% vs. 17%
        5-yr DM 9% vs. 12%
        Severe and acute toxicity similar
        Cetuximab clearly inferior in LRC and OS
        
        De-ESCaLATE-HPV
        
        European study
        Stage III-IV (T3N0, T4N0, T1N1-T2N3) HPV+ oropharynx cancer. Excludes N2b, N2c, >10 PY
        
        :elephant: Cetuximab vs CDDP
        
        endpoint was toxicity :biohazard_sign:
        
        reconfirmed RTOG 1016
        
        →70 Gy in 7 weeks with
        cisplatin
        vs.
        →cetuximab
        2-yr OS 98% vs. 89%
        2-yr any recurrence 16% vs. 6%
        Severe and any grade toxicity similar
        
        p16+ as surrogate for HPV
        
        toxicity events considerable for Cetuximab :elephant: and CDDP
        
        included low risk
        
        TROG 12.01
        
        Australian study
        
        reconfirmed RTOG 1016
        
        More Deintensification Studies
        
        NRG-HN002: Interest in "de-intensification" within RT based context eg "The 60 Gy trial"
        
        randomized phase II for p16+, non/low-smokers, LR advanced OPC
        
        RT only- 60Gy / 5 wks
        
        RT & CDDP - 60 Gy / 6 wks
        
        ChemoRT arm had better PFS (91% vs 88%) and LRC
        
        NRG HN005: Phase II/III deintensification RT for patients with early stage, p16+ nonsmoking OPC
        
        ECOG 1308: Single arm phase II trial of Induction CHT followed by reduced dose and weekly cetuximab :elephant: in patients with HPV associated resectable OPSCC
        
        older study
        
        n = 80
        
        can you give cetuximab, paclitaxel, cistplatin induction to complete response prior to RT with 54gy at primary?
        
        PFS unimpressive 78%
        
        Patients with
        
        < 10 pk year smoking
        
        <T4N2c by AJCC7
        
        PFS was 95%
        
        ECOG 3311; Transoral Endoscopic N&N Surgery :hocho:
        
        randomized phase II trial
        
        in a specific arm: intermediate risk features.
        Resectable oropharynx cancer stage III-IVA AJCC 7, p16+, who undergo TORS
        
        • Low risk (negative margins, no ECE, 0-1 nodes):
        -observation
        • Intermediate risk (close margin <3 mm, 2-4 nodes, ENE ≤1 mm):
        -50 Gy vs. 60 Gy
        • High risk (>1 mm ENE, positive margins, or ≥5 nodes):
        -66 Gy RT weekly cisplatin
        Int Randomized
        
        50 Gy PORT
        
        60 Gy PORT
        
        2-yr PFS (1⁰ endpoint)
        Low risk (obs): 97%
        Int risk (50 Gy vs. 60 Gy): 95% vs. 96%
        High risk (chemoRT): 91%
        3-yr PFS
        Low risk: 97%
        Int risk: 95% and 93%
        High risk: 91%
        (no signficant differences between groups in exploratory comparisons)
        Grade 5 toxicity in n=1
        Decline in QOL and FACT-HN for all arms with recovery to baseline in low-int risk groups, however not for high-risk (P=0.005)
        
        PATHOS
        active European trial
        
        same randomization for intermediate risk as ECOG 3311
        
        60 Gy/30 PORT
        
        50 Gy/25 PORT
        
        High Risk arm randomized for CDDP with PORT vs. PORT alone
        Going to a Phase III with an overall survival endpoint
        
        Mayo DART trial :dart:
        study also looked at PORT
        p16+
        Sx resectable :hocho:
        No DM<10 pack-yr smoking :smoking:
        
        30 Gy (BID) & docetaxol
        
        36 Gy (BID) & docetaxel
        
        in phase 3 it was randomized to 60 Gy w/ or w/o CDDP
        with patients with bilateral disease or ENE
        
        PFS in the 50%s
        
        raised concerns if this, or any deintensification study is adequate after TORS
        
        Comparative study for Chemorad vs TORS upfront
        
        ORATOR: randomized phase 2 of standard CRT vs TORS +adjuvant
        
        Used MDADI swallow instrument for QoL
        
        RT was superior at 1 year, statistically
        
        clinically no difference
        
        but this was the opposite of the expected endpoint (10 point favor to TORS)
        
        PFS similar
        
        1 more item...
        
        HPV Negative disease
        
        the opposite: Intensifications
        
        HPV Intensification: JAVELIN head and neck 100: Chemoradiation combined with anti-PD-1 in LR advanced SCCHN
        
        attempt at intensification
        
        St. III & IVa or IVb SCC
        
        OC
        
        LRx
        
        HPx
        
        OPX p16-
        
        T4, N2c, N3 p16+ OPX
        
        CCDP + RT (70Gy/35)& avelumab
        
        anti PDL1
        
        CDDP + RT & placebo
        
        avelumab underperformed in 1º EP (PFS)
        
        Keynote 412
        Concomitant and Maintenance Pembro
        
        Event free survival, endpoint maturing
        
        SMAC Mimetics
        
        antitumor effects via caspase regulate apoptosis.
        
        apoptosis proteins act on tumor cells
        
        Randomized Phase 2 with CRT with Zuvinipant
        
        met primary endpoint of locoregional control
        
        PFS improved.
        
        currently in phase III
        
        Induction?
        Phase 3 trials showed no benefit over CRT in OPC, Larynx, HPX
        
        Induction is standard for NPC :nose::skin-tone-4:
        
        can use induction for special circumstances.
        
        optimizing for medical status, delays, local issues preventing surgery, very advanced disease.
        
        associated with mortality and worse compliance with CRT
        
        Paradigm: Phase III North America
        
        randomized
        
        Induction Docetaxel CDDP 5FU & CRT
        
        randomized CRT CDDP vs. Docetaxel
        
        CDDP CRT
        
        OS not significant diff
        early study termination due to low accrual
        
        Decide: Phase III North America
        
        TPF regimen induction w/ TPF CRT
        
        TPF CRT
        
        OS not significant diff
        
        Post treatment Followup
        
        PET-NECK
        
        84% OPX, n=564
        
        75% were p16+
        
        PET-CT surveillance :money_with_wings:
        
        planned neck dissection
        
        QoL similar
        
        fewer neck diss. Cheaper :money_with_wings:
        
        PET is now standard
        
        typically 12-14 weeks after RT
        
        so no early false positive
        
        HPV DNA f/u
        
        in HPV +
        
        emerging research, not std of care
        
        promising assay
        
        not yet worked out
- - - - T1 Tumors
        
        LC 85-95%
        • Ultimate LC with surgical salvage ~ 95%
        
        T2 Tumors
        
        LC 65-85%
        • Ultimate LC with surgical salvage about 90%
        • Surgical salvage most often with total laryngectomy
        
        Lateral Opposed Fields :radioactive_sign:
        • If anterior 1⁄2 cord involved and the patient has a thin neck, use 5 mm bolus
        • Make sure there is always anterior flash on skin
        • I recommend using CT based planning with real bolus placed on the field
        • Do not over-wedge or you risk anterior failures
        
        Hypofractionated
        
        Japanese T1N0 fractionation study
        
        Std fx 66Gy/33
        
        63Gy/28fx :trophy:
        
        Local control 5 Y
        77% vs 92%
        Most Desquamation not an issue.
        10% coval cord edema more than 6mo
        
        Korean KROG 0201: T12N0 fractionation study
        
        Hypofx
        
        T1: 63Gy/28fx
        
        T2: 67.5Gy/30fx
        
        standard fx
        
        T1: 66/33
        
        T2: 70
        
        Local PFS
        
        IMRT for early stage
        
        Advantage
        
        Carotid sparing
        
        Disadvantages
        
        Geographical miss from contouring or intrafraction motion
        
        Toxicity from dose inhomogeneity
        
        Voice Quality After Treatment of Early Vocal Cord Cancer :speaking_head_in_silhouette:
        
        Randomized trial
        
        CO2 laser
        
        RT to 66 Gy
        
        60 patients with T1a glottic SCCA in Finland
        
        At 6 and 24 months, compared voice quality, roughness, breathiness, asthenia, strain, videolaryngostroboscopic findings, self-rated voice quality and impact on daily life
        
        Overall voice quality was similar but RT patients showed improvement in breathiness over time, better glottal closure, and less inconvenience in their daily lives
        
        • Conclusion: “Radiation therapy may be the treatment of choice when the requirements for voice quality are demanding.”
        
        Stross says that this isnt a fair comparison if there are multip bx on the same VC. Need to educate patient.
        
        Radonc tables Oral Boards
        2D traditional: (in context of new CTV guidelines, traditional fields may be anachronistic)
        Opposed lat,
        sup=thyroid notch
        inf=bottom of cricoid
        ant=flash
        post=ant VB
        Some rotate gantry to make posterior border non-divergent or place isocenter at anterior edge of vertebral body
        Wedge
        Bolus only if AC involved/bolus if lesion is anterior
        Treatment Planning Slides:
        ISO mid thyroid cart. 4-6MV opp lat
        5-10mm above thyroid notch
        10mm behind thyroid cartilage
        inferior edge of cricoid cart
        1cm flash ant
        T1: 5x5cm box, posterior edge ant to VB
        T2: 6x6cm box posterior edge splitting VB
        GTV, GTV + 2cm to guide block edge, PTV: GTV + 1cm
        95% of PTV gets Rx, No less than 90% dose to PTV
        T1: 63/28
        T2: 65.25/29
      - T3 organ preservation options
        
        Partial laryngectomy
        
        Supracricoid
        
        Supraglottic
        
        Vertical hemilaryngectomy
        
        Partial laryngectomy followed by post-op (chemo)radiation therapy
        
        Chemotherapy with sequential radiation
        
        Concurrent chemoradiation
        
        Total Larrys are not popular
        Partial Larrys are not done in the USA
        
        VA Laryngeal Ca Study 1991
        T34N+
        
        :hocho:Surgery (SOC) followed by RT :radioactive_sign:
        
        Induction CHT :pill:
        
        CR or good PR : RT :radioactive_sign:
        
        good PR: :hocho:surgery
        
        CR: nothing
        
        <PR: :hocho:Surgery then RT :radioactive_sign:
        
        no diff 2 year survival – 68%
        
        Larynx Preservation in 64% in CT-RT group with
        
        Fewer Distant Metastases
        
        Higher Local Recurrence
        
        Salvage in 3/4
        
        Long-term (10yr) Quality of Life Follow-Up
        
        speech significantly better in CT-RT group
        
        same incidence of swallowing difficulties in both groups
        
        Less pain and depression with better global mental health
        
        Surgery first = bad
        Large volume T4a laryngeal cancers did not do well
        
        RTOG 91-11
        Sequential :hocho::pill::radioactive_sign: vs. CRT :pill::radioactive_sign:
        loc: glottic or supraglot
        T: 2, 3, early 4
        N: 0,1,2,3
        neck diss. for >3cm node or multiple nodes 8 wks s/p RT
        exc: T4a
        
        Neoadj CT :pill: + RT :radioactive_sign:
        
        concurrent CRT CDDP :pill::radioactive_sign:
        
        RT only :radioactive_sign:
        
        Different toxicities
        
        Same OS
        
        Concurrent: superior
        
        larynx preservation
        
        LRC
        
        10 y followup shows nonsignificant decrease in OS at ~8 years.
        
        could be toxicity related?
        
        LRC and larynx preserve same at 10y
      - T4 :hocho:
        T4: outer cortex of thyroid cartilage
        
        Full thickness destruction of the thyroid cartilage or extension to BoT :tongue:, reflex :hocho:total laryngectomy
        
        Do poorly with failure of CRT and salvage laryngectomy
        
        T4: extralaryngeal extension
        
        Consider pre-existing function (patient’s age)
        
        Consider volume of tumor e.g. >12cc is concerning
        
        Can consider CRT :pill::radioactive_sign: :
    - - Larynx Preservation in Pyriform Sinus Cancer, Lefebvre
        n = 202
        stage III/IV
        
        :hocho:Surgery then PORT :radioactive_sign:
        
        CDDP/5FU :pill: then
        
        CR: RT 70Gy :radioactive_sign:
        
        54% CR after induction
        
        Local failure: not sig
        
        region failure: not sig
        
        distant mets: Surgery (36% vs. 25%
        
        median OS: CHT: 44 mo vs. 24mo
        
        5y OS: not sig
        
        Larynx preservation: 3y: 42%, 5y:35%
        
        GORTEC Phase III, Pointreau 2009
        more aggressive induction
        Docetaxel/CDDP/5FU vs Cisplatin/5FU ICT in Organ preservation in HPX and larynx Ca.
        
        two ICT regimens
        
        responders get RT alone
        
        nonresponders got surgery :hocho: then RT :radioactive_sign:
        
        laryngeal preservation same
        
        DFS and OS favor TPF
- - - - Taiwan Taichung Veterans Phase III: RT vs CRT
        NPX st. III/IV
        
        RT 70-74 Gy
        
        RT 70-74 Gy + CDDP/5FU
        
        no adjuvant
        
        CRT PFS superior
        
        Is adjuvant necessary?
        
        Sun Yat Sen university, Guangzhou trial, Lancet 2012
        NPX st. III/IV, M0
        exc: T3-T4N0
        n=508
        
        RT +66Gy & CDDP weekly
        
        RT +66Gy & CDDP weekly
        
        adjv CDDP/5FU x 3
        
        no difference in local or distant PFS, OS
        
        is there a role for adjuvant among EBV status patients?
        
        EBV DNA is prognostic
        
        within a week, EBV DNA separates recurrence vs no recurrence
        
        Lin NEJM 2004
        
        NRG HN001: Phase II/III Trial of Individualized treatment for Nasopharynx Ca, based on EBV DNA
        
        post CDDP and RT
        
        Phase III: those undetectable are randomized
        
        Adjuvant CDDP/5FU
        
        observation :telescope:
        
        Phase II: detectable
        
        non resistant consolidation: gem/paclitaxel
        
        CDDP/5FU
        
        this will give us the value of observation in low risk patients
        
        HPV is also prognostic
        
        Stenmark IJROBP 2014
        
        prognosis is worse than EBV
        
        double negative EBV HPV is related to loss of locoregional control.
        
        for EBV we are concerned with metastases
        
        for HPV we are concerned with locoregional control
        
        is induction necessary?
        
        SYS induction trial, Chen JCO 2021
        
        induction gem/CDDP then RT/CDDP x3
        
        no induction
        
        Induction superior
        High compliance
        
        better 3yr distant mets (recurrence) by 7%
        
        OS by 4%
        
        ASCO 2021 NPC Guidelines: NPX cancer, if not induction, then offer Adjuvant CRT
        
        For patients with Stage III-IVA (except T3N0) (AJCC 8th) NPC who do not receive induction chemotherapy plus concurrent chemoradiotherapy, then concurrent chemoradiotherapy plus adjuvant chemotherapy should be offered.