Presentation on theme: "Del Regato Gold Medal 2002, Baltimore, May"— Presentation transcript:
1 Del Regato Gold Medal 2002, Baltimore, May 6 2002 Radiation Therapy, a young centenarian:a diagnosis based upon research achievementsJean-Claude Horiot, M.D., Ph. D.;Centre de Lutte contre le Cancer de Dijon, Université de Bourgogne, Dijon, France.
2 Too much to say… May be I should have selected a simpler topic…. Juan A. del Regato.Other credits.Lessons from (half) a century.From infancy to maturityMissed opportunitiesA few guesses for the near future
3 Juan A. del Regato.Forty-four dollars and 50 cents….The French connectionThe Cuban connectionThe ICR 89 farewell…
4 Forty-four dollars and 50 cents…. A good investment…Cancer, Diagnosis, Treatment and Prognosis Lauren V Ackerman and Juan A. del Regato,1947, 1954, 1962, 1970 editions.One of my four best friends for many years with:Therapeutic radiology, Moss and BrandTextbook of Radiotherapy, G.H. FletcherThe Physics of Radiology, Johns & CunninghamA model I had in mind for the second edition of the Oxford textbook of Oncology.
5 The French connectionThe Del Regato heritage at the « Fondation Curie »:Part of a glorious lineage: Coutard, Regaud, Baclesse, Fletcher, Ennuyer, Bataini and so many pupils all over the world.A deep bilateral sympathy which seems transmitted to Juan del Regato’s US-trained radiation oncologists and Foundation:At least 5/26 of the previous del Regato’s medallists were either French or had an educational French touch…G.H. Fletcher, M. Tubiana, F. Eschwège, A. Dutreix and myself.
6 The Cuban connectionHis name was Augusto GuttierrezSt Joseph Hospital, Houston Texas.1970, 1971, 1972With Gilbert Fletcher, Vera Peters, Luis Delclos and many Spanish speaking friends…
8 Other Credits.Jean Papillon,Gilbert Fletcher and his team,Emmanuel van der Schueren,Members of the EORTC group….
9 Jean Papillon 1914-1993 He was responsible of my RT vocation (1962) the President of my MD thesis (1965)the Director of my french RT training (65-69)an intuitive clinician and researchercapable even beyond retirement of transmittinghis enthusisasm for what he believed inhis achievements in rectal cancers (among many others..)
10 Gilbert H. Fletcher 1911-1992 We met in 1965 in Paris, I had my US training with him from 1969 to 1972,could have worked with him much longer...a genius for synthesis,RT of subclinical diseaseMultidisciplinary approach for strategiesPhysics, Biology and Radiation therapy
11 Emmanuel van der Schueren One of the most effective builders of European Oncology during the last three decades of the XX century.The companion of so many research, education and organisational ventures.My lost best friend.
12 Lessons from (half a) century. From childhood to maturity Fractionation trials (H&N ca, RT alone)Breast cancer (optimisation RT/Surgery)Radio-chemotherapy (H&N, Anus)RT + hormonal treatment: Prostatic Ca
13 Altered fractionation schemes. 20 years of efforts and a beautiful example of translational research before the definition was invented.Hyperfractionation22791Accelerated radiotherapy22851Outside the RT group:Dahanca 7German radiotherapy research groupa meta-analysis to come soon
14 EORTC trials of hyperfractionated and/or accelerated radiotherapy From 1978 to March 1998:2398 patients accrued in phase II and III trials on:Head and neck cancersMalignant GliomasLungBladder, Cervix, Endometrium
15 Conventional vs. Hyperfractionated RT in oropharyngeal carcinoma T2 T3 (excluding base of tongue)N0 or N1 (less than 3 cm)random70 Gy 35 fr 7 wks 80.5 Gy 70 fr 7wksEORTC , 366 patients entered. Updated analysis, April 1998
16 Time to local failure EORTC 22791 April 98 (years) 2 4 6 8 10 12 14 16 246810121416182030405060708090100ONNumber of patients at risk :7915958332371CF631662919HFEORTC 22791Logrank P = 0.022
17 Fibrosis free (grade 3/4) February 98Fibrosis free (grade 3/4)(years)2468101214162030405060708090100ONNumber of patients at risk :1185151CF13567331811HFEORTC 22791Logrank P = 0.905
18 Overall survival EORTC 22791 Logrank P = 0.05 100 90 80 70 60 50 40 30 April 98Overall survival10090EORTC 2279180706050403020(years)10Logrank P = 0.0524681012141618ONNumber of patients at risk :11815975492817941CFHF1131669359362219816
19 Conventional vs. Accelerated RT in Head & Neck carcinoma Advanced (T3/T4 any N, N2/N3 any T, excluding hypopharynx)Amenable to curative RT alonerandom70 Gy 35 fr 7 wks 72 Gy 45 fr 5wksEORTC , 511 patients entered Analysis, August 1995
20 EORTC 22851 Accelerated RT regimen: 72 GY in 5 wks . 3 x 1.6 Gy per day, (4hrs interfractions)Ist course: 28.8 Gy in 7 daysStop 2wks2nd course: 43.2 in 12 days
21 EORTC 22851, Loco-regional control P = 0.019 (logrank test) Conv. RTXAcc. RTX0.80.60.40.24-years local control:CF: 49% ( )AF: 59% ( )246810years
28 Conclusions (1)The radiobiological principles of hyperfractionation and accelerated fractionation are supported by the results of EORTC trials.A 15-20% gain in loco-regional control is obtained.Hyperfractionation with moderate acceleration is transferable to standard practice.The loco-regional control gain now results in a significant improvement of the overall survival in oropharyngeal cancers T2 T3, N0, N1.HF did not increase late normal tissue damage.
29 Conclusions (2) Pure acceleration should be used with caution. Full dose, 3 fractions per day and 5 wks split-course do not allow full repair of sub-lethal damage.Full dose, 2 fractions per day, a 5 to 6 wks RT single course allows the AF delivery in better conditions.Acceleration during the last 2 weeks is also feasible and of benefit (MDAH and RTOG 9003).Working on Saturday (6fr per week) is an alternative…Acceleration with a decrease of the total dose is feasible (CHART). Benefit seems marginal (except for larynx cancers).We have not yet good predictors of tumor response. Progress in that direction is needed to select the patients for AF regimes.
30 3-Years Results of a German Multicenter Randomized Trial Chemoradiation is More Effective than Dose Escalation in Locally Advanced H&N-Cancer -3-Years Results of a German Multicenter Randomized TrialV.Budach1, S. Dinges1, I. Lammert2, M.Stuschke3, H. Sack3, K.-D. Jahnke4, M. Baumann5, T. Herrmann5, W. Budach6, M. Bamberg6, G. Grabenbauer7, P. Wust8, W. Hinkelbein9, H. Frommhold10, J. Dunst11, M.-L. Sauter-Bihl12, K.-D. Wernecke13ARO 95/6 trial, IJROBP 51, 3, Suppl 1, , 20011Strahlenklinik und 2HNO-Klinik, Charité-Campus-Mitte, Berlin; 3Strahlenklinik und HNO-Klinik, UK-Essen; Strahlenkliniken 5UK Dresden; 6UK Tübingen; 7UK Erlangen; 8Charité-Campus-Virchow, Berlin; 9UKBF-Berlin; 10UK Freiburg; 11UC-Halle; GH-Karlsruhe; 13Institut für Medizinische Biometrie, Berlin
33 Overall Survival [OS] (i.t.t.) Last Update: 13.08/01Arm A - RT: Cum. Surv CI Median36 mos % % 15 mos.Log-Rank: p=0.043*; p=0.057**;p=0.029***; Breslow: p=0.029*; p=0.004**;p=0.012***Arm B - CRT: Cum. Surv. CI Median36 mos % % mos.Hazard Ratio B vs. A: 0.80* (Cl: )*stratified per centres**stratified per sites***stratified per sites and centres
34 Conclusion - II Conclusion Accelerated Chemo-RT with 70.6 Gy + MMC/5-FU is more effective than accelerated radiotherapy alone with 77.6 Gy for (univariate Log-Rank-test):Loco-regional Tumor Control (p = 0.004)Overall Survival (p = 0.043)and Progression-free Survival (p = 0.040)Conclusion - IICourtesy of Prof. Volker Budach, MarchLast Update: 12/01
35 Breast cancer: Conservative management 1950: Radical mastectomy +/- RT1970: Simple mastectomy + RT1980: Tumorectomy + RT:Role of RT for in situ diseaseRole of radiotherapy in more advanced TRefinements: Quality of surgery & RT, Cosmesis, Boost?
36 10853 DCIS Trial design DCIS local excision randomisation no further treatmentexternal irradiation50Gy /25 fractions
37 DCIS : Local recurrence (years)24681012142030405060708090100ONNumber of patients at risk :TRT995034513412039741115650747737320610139LELE+RTOverall Logrank test: p<0.001 (HR=0.54)EORTC 10853RTNo RTJulien JP, Lancet 2000
38 Conclusions EORTC trial 10853 At a median follow-up of 6 years, LR rate:LE 20%Overall 15%LE+RT 11%RT allows a the 46% reduction of local recurrence risk (p < 0.001, HR=0.54)Similar reductions of DCIS and invasive recurrencewith a 6 yr-follow-up, no survival difference.Courtesy of Harry Bartelink
39 Boost versus no Boost trial. coordinators: H. Bartelink, J. C Boost versus no Boost trial coordinators: H. Bartelink, J.C. Horiot, E. Van der Schueren, data manager: M. Pierart, statistician: L.ColletteInvasive breast cancer 0-5 cm,post complete excisionno boostExternal RT 50GY R16 Gy boostincomplete not discussedSame with incomplete excision (microscopic)External RT 50 Gy + 10 Gy versus 26 Gy boostEORTC2
41 Data Maturity (analysis July 2000) 5569 patients entered5318 with complete resection (CR)2657 to ‘No boost’ and 2661 to ‘Boost’251 with incomplete resection (IR)Median follow-up 5.1 years54% of patients with CR followed 5 years or more9% of patients with CR followed 10 years or more479/5318 have died so far
42 Breast recurrence free 1009080At 5 years:No boost: 93.2% ( )Boost: % ( )706050403020Overall Logrank test: p=0.0001, HR= % CI: ( )10(years)24681012ONNumber of patients at risk :1822657246417347481271CR No Boost109266125011761749143CR 15 Gy
45 Time to Severe palpable fibrosis in whole breast 1009080706050403020Overall Logrank test: p=0.279010(years)24681012ONNumber of patients at risk :242657250218027891361CR No Boost32266125061785767154CR 15 Gy
46 Time to severe palpable fibrosis (WB or boost) 1009080706050403020Overall Logrank test: p=0.000110(years)24681012ONNumber of patients at risk :372657249817957851361CR No Boost92266124851752749151CR 15 Gy
47 EORTC 22881, Local failure by age years12345678+102030405060708090100Age <= 40p<0.01Age 41-50p=0.02Age 51-60p=0.07Age >60p>0.1156 <=35 and 314 between470 <=40 yearsNo boostBoost
48 Overall Logrank test: p=0.0021 Local controlNo adjuvant treatment1009080706050403020Overall Logrank test: p=0.002110(years)24681012ONNumber of patients at risk :1381911178312935971051CR No Boost90187017721290590108CR 15 Gy
49 Overall Logrank test: p=0.0008 Local controlAdjuvant treatment1009080706050403020Overall Logrank test: p=0.000810(years)246810ONNumber of patients at risk :4474668144115122CR No Boost1979172947115935CR 15 Gy
50 ConclusionsA 16 Gy boost results in a 41% reduction (P<0.001) of the risk of local failure.Young patients have the largest benefit : The 5-year local failure rate drops from 19.5% to 10.2%The risk reduction ranges from 54% in the younger patients to 32% in the older patientsFor patients older than 50, a boost may not be necessaryThis benefit is associated with a slight impairment of the cosmetic outcome.Chemotherapy does not spare the need for the boost.
51 22881: unexpected outcomes. Continuous quality assurance resulted in: Harmonisation of dose prescription and reporting.Improved treatment planning.National recommendations for Surgery/RT techniques and boost indications upon first publication.
52 22881: unexpected outcomes.the huge size and quality of the data base will allow:An unmatched long-term evaluation of late effects and cosmesis.The retrospective analysis of individual genomic abnormalities in specific groups (< 40 year-old, negative nodes and poor prognosis…)
53 Radio-ChemotherapyDemonstration made one or several decades ago in some cancer types (e.g. lymphoma, breast, paediatric oncology…)Was much longer to show up in most solid tumors (Head and neck, cervix, lung, anus, oesophageal cancers)Evidence still missing or questionable in other cancers
54 Jacques Bernier, (Bellinzona, Switzerland) Study coordinator EORTC 22931A phase III randomized study on post-operative radio-chemotherapy in patients with locally advanced head and neck carcinomaJacques Bernier, (Bellinzona, Switzerland) Study coordinator
55 Joint Protocol: Head & Neck, Radiotherapy Groups A phase III randomized trial on post-operative concomitant radio-chemotherapy in patients with locally advanced head and neck Ca (EORTC )Joint Protocol: Head & Neck, Radiotherapy GroupsActivation: February 1994Closure: October 2000Accrual: 334 patientsMedian follow-up: 34 months ( actuarial estimate )
59 EORTC study 22931: Conclusions Patient selection:high risk Head and Neck carcinomapost-operative settingCompared to RT alone, CT-RT yields significantly higher local control and disease-free/overall survival rates, with no undue objective acute toxicity.At a median follow-up of 34 months, it is too early to draw conclusions regarding:time to metastasis and second primaryincidence of late effects in normal tissues
60 data based meta-analysis of randomized MACH-NC, Bourhis et al. 1998:data based meta-analysis of randomizedtrials with chemotherapy in HNSCC# absol. 5 yr-benef. P.adjuvant CT % .74induction CT % .10concurrent CT % <.0001total % <.0001MACH-NC, Institut Gustave Roussy
61 Pending issues: Prognostic factors Biological predictors of tumor responseproliferationresistance to drugsH&N sub-sites and stagesAppropriate assessment of T responseFrail patientsElderly patients
62 Pending issues: optimal management and follow-up of H&N cancers Surgery (mutilating, non-mutilating)?RT alone (including HF, AF, conformal,BT).Concomitant CT-XRT: always better?Optimal strategy per tumor site & sub site?New (chemotherapy?) agents?Reliability of salvage surgery after HF/AF XRT or after concurrent CT-XRT?Quality of life during and after Trt?Cost-effectiveness?
63 Radio-chemotherapy versus Radiotherapy in T3 T4 anal Ca (EORTC 22861), H. Bartelink, study coordinatorEligibility criteriaT3-T4 N0 or any T, N1-N3 proven anal S.C.CarcinomaPS < 2 (WHO) age < 75 yearsno prior cancer or treatmentRandomizationRT: Radiotherapy 45 Gy (1.8 Gy/day, 5 weeks)RT+CX: Same radiotherapy FU 750 mg/m2, d MMC 15 mg/m2 iv, d.1Patients110 recruited eligible (RT: 52, RT+CX: 51)
64 Radio-chemotherapy in locally advanced anal cancer (22861) RESULTS: Colostomy free survival (P = 0.002)110 patientsJCO,1997years
65 Radio-chemotherapy in locally advanced anal cancer (22861) Radiotherapy with concomitant chemotherapy allows:Better local controlImproved colostomy free survivalno difference in overall survivalno difference in acute and late toxicityin a randomized comparison with radiotherapy aloneJCO, Vol 15, No 5, 1997
66 New study: Anal Cancer EORTC 22011-40014 New study: Anal Cancer EORTC (T3T4 or N+ any T) Phase II-III23.4 Gy weeks5FU 200 mg/m²/d1-17MMC 10 mg/m²/d1A36 Gy - 4 weeks5FU 200 mg/m²/d1-26MMC 10 mg/m²/d1Gap2 weeksRB36 Gy - 4 weeksCDDP 25 mg/m²/wd1 - d8 - d15 - d22MMC 10 mg/m²/d123.4 Gy weeksCDDP 25 mg/m²/wd1 - d8 - d15MMC 10 mg/m²/d1
68 EORTC RT AND GU GROUPS (22863) (M. Bolla et al EORTC RT AND GU GROUPS (22863) (M. Bolla et al., N Engl J Med, 337 (5), 1997: )415 patients entered between 1987 and 1995Median duration of follow-up 45 monthsAdjuvant hormonal treatment improves pelvic control & survival (P=0.001)Pelvic RT alone (50 Gy/ 5 weeks +20 Gy boost / 2 weeks) Same Pelvic RT + 3-year adjuvant LHRH (3.6 mg Zoladex s.c. monthly, starting Dl of RT)T1-T2 G3 or T3-T4 any GProstatic Adeno CaR
69 EORTC RT & GU GROUPS 22863 LOCAL CONTROL 97%(93-100%)100RTX + LHRH9080RTX alone7077%(68-86%)60504030P=0.0012010(years)12345678910ONNumber of patients at risk :Treatment30208180127825531191061RTX5207190142111825438187RTX+LHRH
70 EORTC RT & GU GROUPS 22863 OVERALL SURVIVAL 10079%(72-86%)908070RTX + LHRH605062%(52-72%)40RTX alone3020P=0.00110(years)12345678910ONNumber of patients at risk :Treatment58208183139966739231061RTX35207190144111825539197RTX+LHRH
71 Radiotherapy and prostatic cancer coming soon ….In high risk locally curable prostatic cancersEORTC trial : positive margins in resected T3 prostatic Ca: Rt versus observation.Another pivotal trial on hormonal treatment:22961: 3yr vs. 0.5 yr hormonal trt in LA Prostatic Ca as of 9/01: 1110 registered/1100 required
72 Lessons from (half a) century. Missed opportunities Fractionation trialsRectal cancersDeveloping countries
73 A critical look at the practices Has Hyperfractionation become a standard?Yes, however seldom implemented ….
74 Is there an active on-going research? Not really… A critical look at the practices (hyperfractionation and accelerated radiotherapy)Is there an active on-going research?Not really…Other priorities in laboratory and clinical research….Not much demand from the radiotherapy community…...
75 Most RT departments cannot treat twice a day Why did hyperfractionation (either pure or with AF), fail to be implemented?Most RT departments cannot treat twice a dayshortage of equipment and staffproblems of transportation and/or day hospital admissionproblems of expense refunding (health care insurance coverage for a single fraction/day)
76 Why did hyperfractionation fail to be implemented? Some oncologists said they were waiting for duplication of results….but did not change their behaviour when consistent results were published.
77 Why did hyperfractionation failed to become implemented? The major reason however is the challenge of medical oncology trials and the widespread prescription of miscellaneous (often) unproven chemo-radiotherapy regimesThe huge disproportion between the lack of support of a small group of RT equipment manufacturers and the powerful lobby of pharmaceutical industries.
78 We did not loose our time… The combination of radiobiology and clinical experience led to significant progress in our understanding of normal tissues and tumor radiation response.Poor curative radiotherapy is almost eradicated:large fraction sizeinsufficient or too long overall treatment timeinadequate target volumesabsence of quality assurance
79 LessonsSlowly responding normal tissues will express a lower late radiation damage when treated with hyperfractionation .There is a steep dose response curve beyond 70 GyOptimised biological and high precision delivery of radiotherapy are achieved by combining:Hyperfractionation,Reduction of the overall treatment time,Brachytherapy whenever applicableBetter treatment planning (conformal, IMRT)
81 Three dogmas survived a long time (and are not yet dead.…) Upfront surgery is the standard curative management of rectal cancers.The Dukes (or modified Dukes) staging system only allows a realistic estimate of tumor extension.Rectal cancers cannot be cured without surgery
82 EORTC Pre-op trial 40761Surgery vs. pre-operative RT pts.T2 T3 T4 Nx M034,5 Gy/15 fr/18 d, L3, AP/PA.Surgery alone 30% vs. Pre-op 15% p=0.003Conservative surgery: 77 % vs. 86 %Survival benefit in favour of Pre-op in pts with curative resection (69% vs. 59%).5 yr local relapse:Surgery alone 30% vs. Pre-op 15% p=0.003Gérard A et al: Ann Surg 208: , 1984
83 Pre-operative RT in rectal cancers or a missed opportunity to be at least 10 years ahead of time… Next step was to…investigate post-operative radiotherapy rather than to try to improve pre-operative radiotherapy techniques…Reasons behind were mainly driven by the reluctance of surgeons to give up surgery first and rely upon clinical staging.It will take another 13 years before confirmation by Swedish trials of the full benefit (pelvis control + survival) of pre-operative RT...
84 The Swedish rectal cancer trial Improved survivalwith pre-operative radiotherapyin resectable rectal cancer *The New England Journal of Medicine:(1997; 336:980-7.) April 3, 1997.* Dr Lars Pâhlman & al.
85 Surgery alone versus pre-operative Radiotherapy (surgery 1week later) The Swedish rectal cancer trialfrom March 1987 to Feb 1990Patients' selection:Resectable rectal adenocarcinoma (including T1).Age < 80non metastaticStudy design:Surgery alone versus pre-operative Radiotherapy (surgery 1week later)
86 The Swedish rectal cancer trial Radiotherapy scheme:25 Gy in 5 fractions and 5 days4 fields box-techniquePTV: pelvis to L5 included.Accrual:1168 patients accrued from the six regional oncological centres of Sweden (in fact 70 hospitals)
87 27% Surgery alone vs. 11% Pre-operative RT The Swedish rectal cancer trialResultsAt 5 years:Local relapse rate:27% Surgery alone vs. 11% Pre-operative RTp<0.001
88 The Swedish rectal cancer trial ResultsOverall 5 year survival rate:Surgery alone: 48%Pre operative Radiotherapy: 58 % ( p<0.004)9 year cancer specific survival in resectable tumors:Surgery alone: 65 %Pre operative Radiotherapy: 74% ( p<0.002)
89 Dukes A (154/181): 12 % versus 4 % Dukes B (173/195): 23 % versus 10 % The Swedish rectal cancer trialResultsLocal recurrence rate per stage and treatmentSurgery alone versus pre-operative RT:Dukes A (154/181): 12 % versus 4 %Dukes B (173/195): 23 % versus 10 %Dukes C (230/177): 40 % versus 20 %
90 The Swedish rectal cancer trial ConclusionsPreoperative radiotherapy of resectable rectal cancers improves significantly:Loco regional control (of at least 50%)Overall survivalDisease free survival (of about 20%)Preoperative radiotherapy is now the standard approach for clinically staged resectable T2 T3 T4
91 TME ± Pre-op XRT % Local Failures, Follow-up > 2 years XRT + TME TME aloneUpsallaStockholm(3/213) (18/168)Sweden + NorwayConfirmed in 2001 by the Dutch randomised trial.
92 Hopefully trial 22921 should be a landmark for improved strategies. RT in rectal cancersHopefully trial should be a landmark for improved strategies.
93 Two major pending questions in T3T4 rectal cancers: Is concomitant pre-op chemo-radiotherapy better than pre-operative radiotherapy?Is there a need for post-operative chemotherapy in patients having received pre-operative radiotherapy?
94 EORTC TRIAL 22921: a 4-arm multi-factorial design. Pre-op XRT 45 Gy in 5 wks+ 5FU-LV FU-LVSURGERYNo further Trt Post-op Post-op+ 5FU-LV FU-LVCooperative Group of Radiotherapy:J.F. BOSSET Study coordinator
96 Projected completion: early 2003 EORTC TRIAL 22921Status as of April 8, 2002.Entered: 932Required: 992Projected completion: early 2003
97 Lessons from (half a) century. Missed opportunities Developing countries (what a poor name for!)Cervix cancers: expertise and tools are present where disease is vanishing.ISRO: A complex venture.Needs, training, transfer of know-how.Also a main political issue.Their (our?) future lies in our ability to integrate their (research?) priorities with ours (e.g. HPV vaccines for cervix cancer prevention)
99 A few guesses for the near future (1) High precision radiotherapyResulted from a very successful cooperation between radiation oncologists, physicists diagnostic radiologists and industry.Brachytherapy, conformal RT, IMRT are the best chance for the evolution of RT in a fast moving scientific environment
100 Cervical lymph node groups (MSKCC classification) The present … which CTV for the neck ?Cervical lymph node groups (MSKCC classification)Adopted by the Academy’s Committee for Head & Neck Surgery and OncologyRobbins et al, 1991
101 Oropharyngeal Carcinoma Which CTV for the neck?Oropharyngeal CarcinomaStage Ipsilateral neck Contralateral neckN0-N1 II-III-IV + RP for post. II-III-IV + RP for post.pharyngeal wall tumor pharyngeal wall tumorN2a-N2b I1-II-III-IV-V +RP II-III-IV + RP for post.pharyngeal wall tumorN2c According to N stage on According to N stage oneach side of the neck each side of the neckN3 I-II-III-IV-V +RP ± adjacent II-III-IV + RP for post.structures according to clinical pharyngeal wall tumorjudgment1Ib only for N2aCourtesy of V. Grégoire (Brussels)
102 CT-based delineation of lymph node levels in the neck: Brussels-Rotterdam consensus guidelines Level Ia and IbRPLIILIbLIaAnt. symphysis menti / platysmaPost. hyoid bone / submandibular glandLat. ant. belly of digastric m. (Ia)mandible / platysma (Ib)Med. ant. belly of digastric m. (Ib)Cra. geniohyoid m./mandible (Ia)mylohyoid m, submandibular gland (Ib)Cau. hyoid boneCourtesy of V. Grégoire (Brussels)
103 CT-based delineation of lymph node levels in the neck: Brussels-Rotterdam consensus guidelines Level IIAnt. submandibular glandpost. belly of digastric m.Post. sternocleidomastoid m.Lat. sternocleidomastoid m.Med. paraspinal m.int. carotid arteryCra. lateral process of C1Cau. hyoid boneLIbLIILVCourtesy of V. Grégoire (Brussels)
104 CT-based delineation of lymph node levels in the neck: Brussels-Rotterdam consensus guidelines Level IIILVLIIIAnt. sternohyoid m./ sternocleidomastoid m.Post. sternocleidomastoid m.Lat. sternocleidomastoid m.Med. paraspinal m.int. carotid arteryCra. hyoid boneCau. cricoid cartilageCourtesy of V. Grégoire (Brussels)
105 CT-based delineation of lymph node levels in the neck: Brussels-Rotterdam consensus guidelines Level IVAnt. sternocleidomastoid m.Post. sternocleidomastoid m.Lat. sternocleidomastoid m.Med. paraspinal m.int. carotid arteryCra. cricoid cartilageCau. 2 cm cranial to sternoclavicular jointLVILIVCourtesy of V. Grégoire (Brussels)
106 CT-based delineation of lymph node levels in the neck: Brussels-Rotterdam consensus guidelines Level VAnt. sternocleidomastoid m.Post. trapezius m.Lat. platysma / skinMed. paraspinal m.Cra. hyoid boneCau. transverse cervical vesselsLVILIIILVCourtesy of V. Grégoire (Brussels)
107 A few guesses for the near future (2) Treatment individualisation will replace « standard strategies »:3D Imaging linked to high precision RT is one already effective example of that trend.molecular targets involved in radiation damage and repair,the understanding of the intimate mechanisms involved in normal to cancer cell biology,Molecular imaging,Should soon interfere with optimised cancer treatment planning.
108 A few guesses for the near future (3) Two main avenues:Selection of choice of treatment will be influenced by the individual genomic pattern,Novel therapies (e.g. Tyrosine Kinase inhibitors, Cyclin Dependent Kinases, Farnesyl Protein Transferase Inhibitors, anti angiogenesis factors) inactivate proliferation rather than destroy tumors, thus opening a new era for Surgery and Radiotherapy.
109 Guesses for the near future (4) An increasing gap between wealthy countries and the rest of the world…
110 A last word of advice to younger oncologists Remain first a clinician,Never loose track of progress in a faster than ever changing world,Translational research also applies to to radiation oncology.