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Radiothérapie Amiens Actualités VADS 2015

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Actualités 2015 en radiothérapie des cancers des voies aéro-digestives supérieures. Revue subjective des congrès et publications. Présentation CRONOR 21/11/2015. Thèmes : radiochimiothérapie, modification du fractionnement, biothérapie,

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Radiothérapie Amiens Actualités VADS 2015

  1. 1. ACTUALITÉS 2015 en PATHOLOGIE ORL Dr Alexandre COUTTE Radiothérapie – CHU Sud Amiens CRONOR – 21/11/2015
  2. 2. Head & Neck Radiotherapy IMRT Chemotherapy Fractionation TEP & MRI Induction CT Biotherapy Immunotherapy SBRT
  3. 3. PUBLICATIONS VADS 2015
  4. 4. CHIRURGIE  1 Chirurgie-RT vs RT-CT  Analyse à 10 ans des 119 patients randomisés, pas de différence en OS  Opérons les cavités orales et cavités sinusiennes !  Discutons le reste !  2 Curage premier dans les ganglions sans porte d’entrée ?  n = 66 (37 curages puis RT vs 29 RT+/-CT)  Le curage premier augmente le contrôle locorégional sans impact sur la survie globale (96.7% vs 54.1%, p = 0.003)  3 T3-T4 laryngeal cancer in The Netherlands Cancer Institute : 10-year results  60 laryngectomies (T4+++) et 122 RT+/-CT (T3+++)  Pas de différence en survie en fonction du T (5yOS: T3 52%, T4 48%) ou de la stratégie employée (5yOS: RT 50%, CRT 43%, laryngectomie+RT 52%) 1 Gopalakrishna Cancer 2015 2 Amsbaugh ASTRO 2015, Abst 2804 3 Timmermans Head and Neck 2015
  5. 5. CDDP hebdo SERIE BRAS A CDDP 3w (n) BRAS B CDDP w (n) EFFICACITE TOXICITE « VAINQUEUR » Wong ASCO 2015, PD 6019 Prospective MDA 2005-2010 ≥75mg/m2 (757) ≤40mg/m2 (334) A > B p<0,0001 Toxicité limitante Ttt complet = 2/3 3 semaines Dose intensité A > B (p<0,001) Zhang ASCO 2015, P 6035 Méta-analyse (x10) 1982-2015 80-100mg/m2 (390) 30-40mg/m2 (390) A = B 2yOS HR 1,05 (0,61- 1,85) A < B 3w = - de mucites 0 Mohamed ASCO 2015, P 6055 Méta-analyse (x23) 1970-2013 ? mg/m2 (1388) ? mg/m2 (915) A = B 5yOS: 63% (3w) vs 81% (w), p 0,18 A = B G3-5: 56,5% (3w) vs 46% (w), p 0,23 0 Kumar ASTRO 2015, 2773 Inde, Phase IIb 2013-2014 100mg/m2 (31) 40mg/m2 (25) A = B 1yDFS: 80,3% (3w) vs 68,6% (w), p 0,42 A < B Dysphagie A, + importante bras w 0 Compliance Cddp = 35% (3w) vs 60% (w) Melotek ASTRO 2015, 2816 Chicago, Rétrospectif CT à base de platine (144) CBDCA > CDDP (68) Patients + âgés et + de comorbidités A = B LRC: p 0,72 DFS: p 0,28 OS: p 0,71 A > B rein 0 Conclusion : Ref = CDDP 100 mg/m2 (J1-22-43). Il existe d’autres alternatives en cas de CI, de RT hypofractionnée ou de RT accélérée…
  6. 6. RT-CHIMIO vs RT-CETUXIMAB (CTX)  Controverse 2  Le plus souvent, CTX proposé en cas de CI au CDDP, ou sujet âgé (!), ou comorbidités  Equivalence ? Ghi ASTRO 2013  Supériorité du CDDP ? Nombreuses mini-séries rétrospectives monocentriques aux populations pour le moins inégales  CTX réservé aux patients âgés…  Smith ASTRO 2015, A 2855 :  Analyse rétrospective monocentrique de cohorte appariée  CDDP = 48 patients vs CTX = 49 patients  Suivi médian = 2,6 ans  Résultats équivalents entre 2 groupes  Décès / comorbidité = 37% groupe CTX, 0% groupe CDDP  Attente résultats RTOG 1016 pour population oropharynx HPV+
  7. 7. RT-CHIMIO vs INDUCTION-RT-CHIMIO  Controverse 3  L’équivalence n’est pas recherchée  Supériorité induction ? Ghi ASCO 2014  Matuschek ASTRO 2015, A 3168 & Budach ASCO 2014, PD 6012 :  Méta-analyse : 1060 patients, 5 études (critiquables) testant TPFRTCT vs RTCT  Additional induction TPF before RTCT did not result in a significant improvement of overall survival (HR: 0.950, 95% confidence limits (CL) 0.791-1.140, p 0.579)  Attente résultats GORTEC 2007-02 (ASCO 2016) testant TPFRTCTX vs RTCT ASCO 2014
  8. 8. NCIC CTG HN.6 Siu ASCO 2015, Abst 6000  Cancers VADS localement avancés stade III-IV  81% Oropharynx (68% HPV+), 86% N2-3  Pas d’effet p16  Pas de différence en qualité de vie non plus  + de décès autres causes bras RT-CT…?...  Etude négative (cf CONCERT-1 et CONCERT-2) Ringash & al, ASCO 2015, Abst 6053
  9. 9. NIMORAZOLE (Nim) IAEA-Hypox Metwally Radioth Oncol 2015 Dahanca-18 Bentzen Acta Oncol 2015 RTOG 0522 Ang JCO 2014 Design RT acc vs RT acc-Nim 66-70 Gy, 6f/w RT acc-Nim + Cddp week 66-68 Gy, 6f/w RCT acc vs RCT acc-CTX 3 protocols n 43 39 227 444 447 HPV+ (%) Stage III-IV (%) IMRT (%) 7 84 28 5 90 33 51 79 * 36 100 86 39 100 87 2y OS 51 29 82 80 83 2y PFS * * 76 64 63 2y LRC 48 44 83 83 78 EORTC 1219 / DAHANCA 29 compare schéma Dahanca-18 avec schéma sans Nim, population HPV-
  10. 10. HPV Effet de la dose intensité du CDDP associé à la radiothérapie en fonction du statut HPV  n = 659, PMH (584) & Istituto Nazionale dei Tumori (75)  HPV+ = 61%, HPV- = 39%  Dose intensité = rôle majeur chez HPV- (cf RTOG 0129 et GORTEC 99-02)  Pas d’impact pour HPV+ = déflation ????? Spreafico ASCO 2015, Abst 6020
  11. 11. PATIENTS AGES  Suivi médian = 5,2 ans, N = 2688 :  RTOG 9003 (modification fractionnement, 4 bras)  RTOG 0129 (RCT vs RCT accérélée)  RTOG 0522 (RCT vs RCT-Cetuximab)  Pas de différences de toxicité si RT seule  RCT : plus de thrombopénie (p=0,02), d’anémie (p=0,03), de néphrotoxicité (p=0,06), mais moins de mucites (p=0,04)  Les patients âgés de 70 ans et plus traités par RCT avec cisplatine ont une survie réduite liée à des défaillances d’organe, notamment cardio-pulmonaires  La RCT avec cisplatine n’est pas recommandée chez les patients âgés  RTOG 91-11 et protocoles associés avec troubles de déglutition tardifs et sévères  Essais ELAN !!!! Kish ASCO 2015, Abst 6003 Ward ASCO 2015, Abst 1140
  12. 12. PATIENTS AGES  Suivi médian = 5,2 ans, N = 2688 :  RTOG 9003 (modification fractionnement, 4 bras)  RTOG 0129 (RCT vs RCT accérélée)  RTOG 0522 (RCT vs RCT-Cetuximab)  Pas de différences de toxicité si RT seule  RCT : plus de thrombopénie (p=0,02), d’anémie (p=0,03), de néphrotoxicité (p=0,06), mais moins de mucites (p=0,04)  Les patients âgés de 70 ans et plus traités par RCT avec cisplatine ont une survie réduite liée à des défaillances d’organe, notamment cardio-pulmonaires  La RCT avec cisplatine n’est pas recommandée chez les patients âgés  RTOG 91-11 et protocoles associés avec troubles de déglutition tardifs et sévères  Essais ELAN !!!! Kish ASCO 2015, Abst 6003 Ward ASCO 2015, Abst 1140
  13. 13. RT-3D vs IMRT  Princess Margaret Hospital, 2000  2010  n = 181 hypopharynx  IMRT > 3D pour LRC sans traduction en OS Mok Head and Neck 2015
  14. 14. FRACTIONNEMENT  La seule modification du fractionnement ne peut raisonnablement compenser l’absence de chimiothérapie  Gupta Clin Oncol 2015 :  Méta-analyse (5 études – 1117 patients)  RT-CT conventionnelle vs RT à fractionnement modifié  Budach IJROBP 2015 :  n = 384, RT hyperfractionnée accélérée HART (70.6 Gy) + CT > HART (77.6 Gy)
  15. 15. TEP (1)  1-2 Curage systématique ou TEP à S12 ?  Survie identique  Le TEP est moins onéreux  Moins de complications avec le TEP !  Les patients HPV+ ont une meilleure QOL que HPV+ mais qui se détériore plus vite à la phase aigue… 1 Mehanna ASCO 2015 – Abst 6009 2 Mehanna ECC-ESMO 2015 – Abst 11 LBA HR = 0,92 (0,65-1,32) OverallSurvival
  16. 16. TEP (2)  3 Etude DDFMISO  2 cohortes (25+25), RT-CT hyperfractionnée, HPV- (82%)  Définition d’un paramètre robuste basé sur la réoxygénation individuelle, avec un seuil de 20 % à S2  4 A Prospective Phase 2 Study of SPECT/CT-guided Volume De-escalation  Irradiation prophylactique inutile dans une large proportion de cous cN0  n=21, SPECT/CT après injection de 99mTc autour de la tumeur  les régions du cou comprenant jusqu’à 4 ganglions sentinelles étaient incluses dans le CTV et traitées (CTVSPECT <<<<< CTVstandard)  Suivi médian = 14 mois, pas de récidive régionale, 2 récidives locales, dose diminuée aux OAR 3 Seidlitz ECC-ESMO 2015 – Abst 10 LBA 4 Longton ASTRO 2015 – 161
  17. 17. DELINEATION  1 Enfin !  2 18FDG-TEP-planification < CT-planification (volumes)  41 patients & 3 centres (Bruxelles UCL, Namur, Lille)  Segmentation automatique GTVTEP  CTVs  PTVs  dosi  ttt  Puis rétrospectivement délinéation GTVCT  CTVs  PTVs  comparaison  3y OS = 43% et 0 récidive dans CTVCT et hors CTVTEP 1 Brouwer Radioth Oncol 2015 2 Leclerc Radioth Oncol 2015
  18. 18. CAVUM  MACH-NPC  19 études  4806 patients  +++ concomitant plus adjuvant (HR 0·65, 0·56–0·76)  ++ concomitant (HR 0·80,0·70–0·93)  - adjuvant (HR 0·87, 0·68–1·12)  --- induction (HR 0·96, 0·80–1·16)  Wang Radioth Oncol 2015  2679 cas revus rétrospectivement avec nouvelle classification (répartition en %)  Suggestions / rapport aux épidermoïdes : augmenter limite craniale niveau II & limite postérieure niveau V Induction Adjuvant Concomitant + AdjuvantConcomitant Blanchard Lancet Oncol 2015 0 4,3 67,1 87,4 44,2 13,1 1 37,1 37,1 44,2 1,8 0 0 0 75,16,62 0,1 0,1 0,1 0,1 0,1 2
  19. 19. RÉIRRADIATION Author / Center Reference n Radiation Therapy Recurrence/ 2nd primary (%) Postop / Definitive (%) CT (%) Median OS (m) OS / DFS / LRC Toxicities (%) Edson / MDA ASCO 6065 72 134 IMRT > 60 Gy IMRT > 60 Gy + CT +/- induction * * 0 100 * * 5y : 49 / * / 55 5y : 35 / * / 69 Grade 4-5  8 Grade 4-5  28 Kevelin / Mayo Cl ASCO 6064 89 Postop, median = 60 Gy Definitive, median = 69,6 Gy 75 / 25 53 / 47 74 22,2 < 60 Gy : 9,5 > 60 Gy : 25,2 2y : 47 / * / 61 * Garg / Winston Salem Head and Neck 50 IMRT = 72% Median = 60 Gy 68 / 32 46 / 54 40 18 1y : 41 / 33 / 53 Grade 4-5  14 Ramasamy / PMH ASTRO 2776 85 IMRT = 88% Hyperfractionated 44-66 Gy = 82% 66 / 34 60 / 40 25 * 2y : 52 / * / 88 Grade 3-5  7 Yao / Multi-site ASTRO 1143 46* IMRT CTV = 60 Gy & GTV = 66 Gy * 100 Ctx Ddp * 1y : 64 / 37 / * Grade 3-4  22 (?) Zakem / Cleveland ASTRO 2850 32 IMRT Postop, median = 64 Gy IMRT Definitive, median = 72 Gy 72 / 28 40 / 60 81 * 2y : * / * / 67,6 Grade 3-5  25 Zhang / Long Island ASTRO 1036 41 SBRT Postop, median = 35 Gy / 5 f SBRT Definitive, median = 40 Gy / 5 f 100 / 0 46 / 54 0 * 1y : 53 / * / 90 Grade 3-5  2 Vargo / Pittsburgh IJROBP 48* Cyber 35% - Trilogy 23% - TBeam 42% Median = 40-44 / 5 f 79 / 21 67 / 33 100 Ctx 10 1y : 40 / 33 / 37 Grade 3-4  6 Kress / Georgetown Head and Neck 85 SBRT - Cykerknife Median = 30 Gy / 5 f 87 / 13 29 / 71 70 12,2 2y : 24 / * / 28 Grade 3-5  5,9 * phase II Ctx = Cetuximab Ddp = Cisplatin weekly 30 Intervalle RT1-RT2 Second cancer = meilleure survie vs récidive Chirurgie dès que possible Dose > 60 Gy Volume limités Faut-il ajouter CT conco ? IMRT = oui, SBRT ?
  20. 20. CONCLUSION  CDDP 100 mg/m2 J1-22-43 = standard en RT-CT  Vie, mort et sans résurrection du Panitumumab (en ORL !)  HPV + = faire moins ? & HPV - = faire plus ?  Alors que revoilà l’hypoxie ! Affaire à suivre  TEP à S12 post RT-CT = standard  Est-ce que les patients âgés bénéficient au moins de l’irradiation ?  Le contourage : qui peut le moins  La réirradiation : peu de bénéficiaires mais avec quel protocole ?

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