Recent trends in radiotherapy for advanced head and neck carcinoma ! Phuc Félix Nguyen-Tân MDCM, FRCP(C) ! Assistant Professor ! Department of Radiation-Oncology ! CHUM Notre-Dame !
Goal of Radiotherapy ! • Treat the target volume while sparing normal tissue !
Intensity-Modulated Radiotherapy (IMRT) ! Radiotherapy delivered with variable beam intensities across the irradiated field !
Conventional Radiotherapy ! Conventional ! Beam Shaper ! Actual Dose Desired Dose Distribution ! Distribution !
Principles of IMRT ! • Each broad radiation beam is divided into a number of smaller beams (beamlets) • Intensities of neighboring beamlets differ • Beams/beamlets enter target from different angles and combine to deliver conformal dose
Intensity Modulated Radiotherapy (IMRT) ! Intensity ! Transmitted ! Modulator ! Beamlets ! Desired Dose Actual Dose Distribution ! Distribution !
Intensity Map ! Port Film ! E.H. !
Patient Immobilization !
30%, 50%, 75%, 88% ! 30%, 50%, 70%, 85% !
BEV 240 ! BEV 80 ! BEV AP !
Advantages of IMRT ! • High dose volume conforms to the 3-D configuration of the tumor ! • Sparing of nearby normal tissues ! • Option for tumor dose escalation ! • Biologically more effective dose to tumor ! • Improved therapeutic ratio !
Potential Disadvantages ! • Requires greater technical expertise ! • Labor intensive ! • Time consuming ! • Greater target dose inhomogeneity ! • Requires reproducible immobilization ! • More stringent Quality Assurance !
IMRT Methods ! • SMLC : Segmental Multileaf Collimator ! step-and-shoot, stop-and-shoot, ! multisegment ! • DMLC : Dynamic Multileaf Collimator ! sliding window technique ! • IMAT : Intensity-Modulated Arc Therapy ! • Tomotherapy : Sequential (Peacock) ! Helical !
IMRT vs conventional XRT for advanced oropharyngeal carcinoma: The Notre-Dame experience ! (Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):582-9) !
Rational for using IMRT ! • Target delineation improved ! • Dose volume more conformal to the target volume ! • Dose per fraction higher to GTV ! • Treatment time shorter ! • Mean dose higher ! • Better therapeutic ratio !
Objectives ! • Compare acute toxicity and initial response of IMRT vs conventional XRT for patients with advanced carcinoma of the oropharynx treated with concurrent chemotherapy !
Materials ! • 249 patients with oropharyngeal carcinoma ! • 194 men (78%) et 55 women (22%) ! • Median age 57 y.o. (range: 31-79) ! • Stage III (12%) and stage IV (88%) ! • Two groups studied: ! • 100 patients with IMRT ! • 149 patients conventional XRT !
Materials ! • IMRT: ! – 70 Gy in 33 fractions of 2.12 Gy per day ! – Mean dose 73 Gy ! – 6 and a half weeks ! • Conventional XRT ! – 70 Gy in 35 fractions of 2 Gy per day ! – 7 weeks !
Materials ! • Chemotherapy: ! – Carboplatin (70 mg/m2/d x 4 days bolus) ! 5FU ( 600 mg/m2/d continuous infusion) ! !
Results !
IMRT results ! Author ! Site ! No. Patients ! Follow-up Control ! (months) ! Chao ! Oropharynx ! 74 ! 33 ! 87% ! Lee ! Oropharynx ! 41 ! 31 ! 95% ! Eisbruch ! Varied ! 60 ! 32 ! 82% ! De Arruda ! Oropharynx ! 50 ! 18 ! 98% ! Mendenhall ! Base of 22 ! 24 ! 90% ! tongue ! Mendenhall ! Tonsil ! 17 ! 37 ! 100% ! Notre-Dame ! Oropharynx ! 100 ! 35 ! 92% !
Experience with sw-IMRT ! Local F/U control median( Studies Centers N Dose to parotids Xero ≥ Gr2 (%) month) Washington Chao et al 74 33 87 < 26 Gy 30% university De Arruda et 2 Pd <26Gy (26%) 33% MSKCC 50 18 98 al. 1 Pd <26Gy (72%) à 9 months M.D. Anderson Pd Ipsi : <26 Gy Cancer Setton et al. 442 37 95 28% at 3 yr Pd Contro:<22Gy center Pd (lobe sup): mean = Huang et al. USCF 71 33 94 33% at 2 yr 25,5 Gy 1 Pd <26 Gy 2 Pd >20cc <20Gy Clavel et al. CHUM 100 33 95 20% at 2 yr 2 Pd 50% <30Gy
Sw-IMRT vs conventional RT ! Median Doses to parotids Study Centers N F/U LCR (%) Xéro ≥ Gr2 (Gy) (month) PARSPORT Nutting et al., No diff 74% vs 38% (multi- 94 44 Pd Contro: < 24Gy The Lancet (1an) 12 months centrique) oncology 2011 1 Pd <26 Gy 95 82% vs 31% Clavel et al. CHUM 2 Pd >20cc <20Gy 249 42 vs 85 IJROBP 2011 1 year (p=0.042) 2 Pd 50% <30Gy
Conclusion ! • Less grade 3-4 radiodermatitis with IMRT ! • More grade 3-4 mucositis with IMRT ! • Other acute toxicities similar with conventional XRT ! • Better usage of radiobiological principles with IMRT could lead to potential improvement in locoregional control ! • Predict that long term toxicities might decrease, especially xerostomia ! • Potential for better quality of life ! • Effect is difficult to quantify with concurrent chemotherapy !
¹⁸ F-FDG-PET imaging in radiotherapy tumor volume delineation in treatment of head and neck cancer (Radiother Oncol 2011 Dec;101(3):362-8) !
Objectives/Method ! • Prospective study ! • Evaluate impact of PET/CT to CT alone ! • 29 patients with H&N carcinoma ! • PET-CT done at planification ! • Images reviewed independently ! • Contours done in collaboration with neuroradiologist and nucleist on CT then PET ! – GTV primary et GTV nodes !
Volume of GTVp: CT vs TEP ! • CT • TEP p=0.001
Example of GTV ! • CT • TEP
Volumes of GTVgg: CT vs TEP • CT ! • TEP p=0.08
Negatif adnp on CT and positive on PET ! Ultrasound guided bx: 0/8 were positive !
Metastasis found incidentally !
Conclusions ! • Volume of primary GTV ! – CT > TEP in 80% of cases ! • No difference in volume for adenopathies ! • Treatment altered in 14% of pts ! • Influence on clinical outcome? ! – Potential for decrease toxicities ! – Potential for better locoregional control and survival ! – More studies required !
Is Helical Tomotherapy (HT) superior to sw-IMRT for advanced oropharyngeal carcinoma? The CHUM Notre-Dame experience !
Apparatus and software ! – sw-IMRT: - Eclipse ! ! ! - CORVUS ! ! ! ! – TH: - Helical tomotherapy !
TH vs dose to parotids ! ! Numerous dosimetric studies shown decreased dose to the parotid when comparing sw-IMRT to TH ! ! ! ! ! ! ! ! !
Hypothesis ! • TH compared to sw-IMRT will diminish the dose to the parotids which will translate to similar locoregional control while clinically decrease the incidence of longterm xerostomia !
Objectives " Compare the dose received to the parotids in patients with advanced oropharyngeal carinoma treated with sw-IMRT vs TH and concomittant chemotherapy ! Compare longterm xerostomia in each group and correlate this with the dose received to the parotids and the XRT technique "
Retrospective study " Eligibility criteria " – Treatments between January 2007 and September 2010 at Notre-Dame Hospital CHUM ! – Locally advanced oropharyngeal ca ! – Curative intent ! – Concomittant chemotherapy with platinum regimen !
Treatment: ! Volumes ! • GTV (Gross tumor volume): primary and adp " " " • CTV1 (clinical tumor volume): ! Tumor + margin + lymphatic drainage ! at high risk ! ! • CTV2: lymphatic drainage at low risk " • PTV1: (Planning target volume): CTV1 + 3-5 mm ! • PTV2: CTV2 + 3-5 mm "
Treatments: ! • Dose " • GTV: 70 Gy in 33 fractions of 2,12 Gy ! • CTV1: 59,4 Gy in 33 fractions of 1,8 Gy " • CTV2: 50,4 Gy in 28 fractions of 1,8 Gy "
Results ! – N = 89 (sw-IMRT = 45 vs TH = 44) ! – Median follow-up 26 months ! !
Locoregional control ! Median F/U 26 months ! !
TH vs mean dose to ipsilateral parotids ! P<0,0001
TH vs dose controlateral parotid ! P<0,0001
Grade of xerostomia: sw- IMRT vs TH ! 100% 90% 80% Grade 3 Grade 2 70% Grade 1 60% Grade 0 50% 40% 30% 20% 10% P < 0,001 0% sw-IMRT 6 mois sw-IMRT 12 mois HT 6 mois HT 12 mois
Discussion ! • Multivariate analysis demonstrated in this series that the XRT technique and the dose to the parotid were the two most predictive factor for the degree of xerostomia ! • IMRT techniques which allow for better sparing of normal tissue such as the parotids leads potentially to a better therapeutic ratio !
Conclusion ! • Recent advances in radiotherapy techniques has translated into better clinical outcome including quality of life issues ! • Evaluation of new technologies is of prime importance to justify not only its clinical relevance but also its costs !
Patients characteristics !
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