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Del Regato Gold Medal 2002, Baltimore, May 6 2002 Radiation Therapy, a young centenarian: a diagnosis based upon research achievements Jean-Claude Horiot,

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Presentation on theme: "Del Regato Gold Medal 2002, Baltimore, May 6 2002 Radiation Therapy, a young centenarian: a diagnosis based upon research achievements Jean-Claude Horiot,"— Presentation transcript:

1 Del Regato Gold Medal 2002, Baltimore, May Radiation Therapy, a young centenarian: a diagnosis based upon research achievements Jean-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 maturity –Missed opportunities A few guesses for the near future

3 Juan A. del Regato. Forty-four dollars and 50 cents…. The French connection The Cuban connection The 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 Brand –Textbook of Radiotherapy, G.H. Fletcher –The Physics of Radiology, Johns & Cunningham A model I had in mind for the second edition of the Oxford textbook of Oncology.

5 The French connection The 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 Regatos US-trained radiation oncologists and Foundation: –At least 5/26 of the previous del Regatos medallists were either French or had an educational French touch… –G.H. Fletcher, M. Tubiana, F. Eschwège, A. Dutreix and myself.

6 The Cuban connection His name was Augusto Guttierrez St Joseph Hospital, Houston Texas. 1970, 1971, 1972 With Gilbert Fletcher, Vera Peters, Luis Delclos and many Spanish speaking friends…

7 The ICR 89 farewell…

8 Other Credits. Jean Papillon, Gilbert Fletcher and his team, Emmanuel van der Schueren, Members of the EORTC group….

9 Jean Papillon 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 researcher capable even beyond retirement of transmitting his enthusisasm for what he believed in his achievements in rectal cancers (among many others..)

10 Gilbert H. Fletcher 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 disease Multidisciplinary approach for strategies Physics, 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. Hyperfractionation –22791 Accelerated radiotherapy –22851 Outside the RT group: –Dahanca 7 –German radiotherapy research group –a 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 cancers –Malignant Gliomas –Lung –Bladder, Cervix, Endometrium

15 Conventional vs. Hyperfractionated RT in oropharyngeal carcinoma T2 T3 (excluding base of tongue) N0 or N1 (less than 3 cm) random 70 Gy 35 fr 7 wks80.5 Gy 70 fr 7wks EORTC 22791, 366 patients entered. Updated analysis, April 1998

16 Time to local failure April 98 (years) ONNumber of patients at risk : CF HF EORTC Logrank P = 0.02

17 Fibrosis free (grade 3/4) February 98 (years) ONNumber of patients at risk : CF HF EORTC Logrank P = 0.90

18 Overall survival April ONNumber of patients at risk : CF HF EORTC Logrank P = (years)

19 Conventional vs. Accelerated RT in Head & Neck carcinoma Advanced (T3/T4 any N, N2/N3 any T, excluding hypopharynx) Amenable to curative RT alone random 70 Gy 35 fr 7 wks72 Gy 45 fr 5wks EORTC 22851, 511 patients entered Analysis, August 1995

20 EORTC Accelerated RT regimen: 72 GY in 5 wks. 3 x 1.6 Gy per day, (4hrs interfractions) Ist course: 28.8 Gy in 7 days Stop 2wks 2nd course: 43.2 in 12 days

21 EORTC 22851, Loco-regional control P = (logrank test) years Conv. RTX Acc. RTX

22 EORTC 22851, Specific Survival p=0.06

23 ONNumber of patients at risk : CF AF Logrank P < (years) Time without severe late toxicity (EORTC 22851) AF CF

24 Time without severe connective tissue damage P < (logrank test)

25

26 FRACTIONATION STUDIES IN HEAD & NECK CANCER

27

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 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. Conclusions (2)

30 Chemoradiation is More Effective than Dose Escalation in Locally Advanced H&N-Cancer - 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 Trial V.Budach 1, S. Dinges 1, I. Lammert 2, M.Stuschke 3, H. Sack 3, K.-D. Jahnke 4, M. Baumann 5, T. Herrmann 5, W. Budach 6, M. Bamberg 6, G. Grabenbauer 7, P. Wust 8, W. Hinkelbein 9, H. Frommhold 10, J. Dunst 11, M.-L. Sauter-Bihl 12, K.-D. Wernecke 13 ARO 95/6 trial, IJROBP 51, 3, Suppl 1, , Strahlenklinik und 2 HNO-Klinik, Charité-Campus-Mitte, Berlin; 3 Strahlenklinik und HNO-Klinik, UK-Essen; Strahlenkliniken 5 UK Dresden; 6 UK Tübingen; 7 UK Erlangen; 8 Charité-Campus-Virchow, Berlin; 9 UKBF-Berlin; 10 UK Freiburg; 11 UC-Halle; GH-Karlsruhe; 13 Institut für Medizinische Biometrie, Berlin

31 10 Gy/ 2 Gy 20 Gy/ 2 Gy 30 Gy/ 2 Gy 44 Gy/ 2x 1.4 Gy 58 Gy/ 2x 1.4 Gy 70,6 Gy/ 2x 1.4 Gy Arm B WE X 5-FU, 600mg/m 2 c.i. MMC, 10mg/m 2 10 Gy/ 2 Gy 21,6 Gy/ 2 / 1.4 Gy 35,6 Gy/ 2x 1.4 Gy 49,6 Gy/ 2x 1.4 Gy 63,6 Gy/ 2x 1.4 Gy 77,6 Gy/ 2x 1.4 Gy WE Arm A xxxxx V. Budach et al., DEGRO 2001 ARO Study STRATA (Centers, tumor site, N-stage)

32

33 Arm A - RT:Cum. Surv. CIMedian 36 mos. 30.6% % 15 mos. Overall Survival [OS] (i.t.t.) Last Update: 13.08/01 Hazard Ratio B vs. A: 0.80* (Cl: ) Arm B - CRT: Cum. Surv. CI Median 36 mos. 36.9% % 23 mos. Log-Rank: p=0.043*; p=0.057**;p=0.029***; Breslow: p=0.029*; p=0.004**;p=0.012*** *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)Loco-regional Tumor Control (p = 0.004) Overall Survival (p = 0.043)Overall Survival (p = 0.043) and Progression-free Survival (p = 0.040)and Progression-free Survival (p = 0.040) Last Update: 12/01 Courtesy of Prof. Volker Budach, March 2002.

35 Breast cancer: Conservative management 1950: Radical mastectomy +/- RT 1970: Simple mastectomy + RT 1980: Tumorectomy + RT : –Role of RT for in situ disease –Role of radiotherapy in more advanced T –Refinements: Quality of surgery & RT, Cosmesis, Boost?

36 10853 DCIS Trial design DCIS local excision randomisation no further treatment external irradiation 50Gy /25 fractions

37 DCIS : Local recurrence Julien JP, Lancet 2000 (years) ONNumber of patients at risk :TRT LE LE+RT Overall Logrank test: p<0.001 (HR=0.54) EORTC RT No RT

38 Conclusions EORTC trial At a median follow-up of 6 years, LR rate: LE 20% Overall15% 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 recurrence with a 6 yr-follow-up, no survival difference. Courtesy of Harry Bartelink

39 Boost versus no Boost trial. coordinators: H. Bartelink, J.C. Horiot, E. Van der Schueren, data manager: M. Pierart, statistician: L.Collette EORTC Invasive breast cancer 0-5 cm, post complete excision no boost External RT 50GY R 16 Gy boost Same with incomplete excision (microscopic) External RT 50 Gy + 10 Gy versus 26 Gy boost

40 EORTC BOOST TRIAL (BREAST CANCER) 5,569 patients( ) France 1185 UK 146 Belgium 817 NL 2603 Switzerland 306 Israel 102 Spain 21 Germany 374

41 Data Maturity (analysis July 2000) 5569 patients entered –5318 with complete resection (CR) 2657 to No boost and 2661 to Boost –251 with incomplete resection (IR) Median follow-up 5.1 years –54% of patients with CR followed 5 years or more –9% of patients with CR followed 10 years or more 479/5318 have died so far

42 (years) ONNumber of patients at risk : CR No Boost CR 15 Gy Breast recurrence free Overall Logrank test: p=0.0001, HR= % CI: ( ) At 5 years: No boost: 93.2% ( ) Boost: 95.7% ( )

43 Local Failures

44 Fibrosis in whole breast (worst grade)

45 (years) ONNumber of patients at risk : CR No Boost CR 15 Gy Time to Severe palpable fibrosis in whole breast Overall Logrank test: p=0.2790

46 (years) ONNumber of patients at risk : CR No Boost CR 15 Gy Time to severe palpable fibrosis (WB or boost) Overall Logrank test: p=0.0001

47 EORTC 22881, Local failure by age No boost Boost

48 (years) ONNumber of patients at risk : CR No Boost CR 15 Gy Local control No adjuvant treatment Overall Logrank test: p=0.0021

49 (years) ONNumber of patients at risk : CR No Boost CR 15 Gy Local control Adjuvant treatment Overall Logrank test: p=0.0008

50 Conclusions A 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 patients For patients older than 50, a boost may not be necessary This 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-Chemotherapy Demonstration 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 EORTC A phase III randomized study on post-operative radio-chemotherapy in patients with locally advanced head and neck carcinoma Jacques Bernier, (Bellinzona, Switzerland) Study coordinator

55 A phase III randomized trial on post-operative concomitant radio-chemotherapy in patients with locally advanced head and neck Ca ( EORTC 22931) Joint Protocol:Head & Neck, Radiotherapy Groups Activation:February 1994 Closure: October 2000 Accrual:334 patients Median follow-up: 34 months ( actuarial estimate )

56 Treatment scheme

57

58

59 EORTC study 22931: Conclusions Patient selection:Patient selection: –high risk Head and Neck carcinoma –post-operative setting Compared to RT alone, CT-RT yields significantly higher local control and disease-free/overall survival rates, with no undue objective acute toxicity.Compared 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:At a median follow-up of 34 months, it is too early to draw conclusions regarding: – time to metastasis and second primary – incidence of late effects in normal tissues

60 MACH-NC, Institut Gustave Roussy MACH-NC, Bourhis et al. 1998: data based meta-analysis of randomized trials with chemotherapy in HNSCC # absol. 5 yr-benef.P. adjuvant CT %.74 induction CT %.10 concurrent CT % <.0001 total % <.0001

61 Pending issues: Prognostic factors Biological predictors of tumor response –proliferation –resistance to drugs H&N sub-sites and stages Appropriate assessment of T response Frail patients Elderly 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 coordinator Eligibility criteria n T3-T4 N0 or any T, N1-N3 proven anal S.C.Carcinoma n PS < 2 (WHO) - age < 75 years n no prior cancer or treatment Randomization n RT: Radiotherapy 45 Gy (1.8 Gy/day, 5 weeks) n RT+CX: Same radiotherapy + 5FU 750 mg/m2, d MMC 15 mg/m2 iv, d.1 Patients n 110 recruited eligible (RT: 52, RT+CX: 51)

64 Radio-chemotherapy in locally advanced anal cancer (22861) RESULTS: Colostomy free survival ( P = 0.002) years 110 patients JCO,1997

65 Radio-chemotherapy in locally advanced anal cancer (22861) Radiotherapy with concomitant chemotherapy allows: B etter local control I mproved colostomy free survival no difference in overall survival no difference in acute and late toxicity in a randomized comparison with radiotherapy alone JCO, Vol 15, No 5, 1997

66 New study: Anal Cancer EORTC (T3T4 or N+ any T) Phase II-III 36 Gy - 4 weeks 5FU 200 mg/m²/d1-26 MMC 10 mg/m²/d1 R A B 36 Gy - 4 weeks CDDP 25 mg/m²/w d1 - d8 - d15 - d22 MMC 10 mg/m²/d1 Gap 2 weeks 23.4 Gy weeks 5FU 200 mg/m²/d1-17 MMC 10 mg/m²/d Gy weeks CDDP 25 mg/m²/w d1 - d8 - d15 MMC 10 mg/m²/d1

67 RT + hormonal treatment: Prostatic ca

68 EORTC RT AND GU GROUPS (22863) (M. Bolla et al., N Engl J Med, 337 (5), 1997: ) 415 patients entered between 1987 and 1995 Median duration of follow-up 45 months Adjuvant 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) R T1-T2 G3 or T3-T4 any G Prostatic Adeno Ca

69 EORTC RT & GU GROUPS LOCAL CONTROL (years) ONNumber of patients at risk :Treatment RTX RTX+LHRH 97% (93-100%) 77% (68-86%) P=0.001 RTX + LHRH RTX alone

70 EORTC RT & GU GROUPS OVERALL SURVIVAL (years) ONNumber of patients at risk :Treatment RTX RTX+LHRH P= % (72-86%) 62% (52-72%) RTX + LHRH RTX alone

71 Radiotherapy and prostatic cancer coming soon …. In high risk locally curable prostatic cancers EORTC 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 trials Rectal cancers Developing countries

73 Has Hyperfractionation become a standard? Yes, however seldom implemented …. A critical look at the practices

74 Is there an active on-going research? Not really… Other priorities in laboratory and clinical research…. Not much demand from the radiotherapy community…... A critical look at the practices (hyperfractionation and accelerated radiotherapy)

75 Why did hyperfractionation (either pure or with AF), fail to be implemented? Most RT departments cannot treat twice a day –shortage of equipment and staff –problems of transportation and/or day hospital admission –problems 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 regimes The 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 size –insufficient or too long overall treatment time –inadequate target volumes –absence of quality assurance

79 Lessons Slowly responding normal tissues will express a lower late radiation damage when treated with hyperfractionation. There is a steep dose response curve beyond 70 Gy Optimised biological and high precision delivery of radiotherapy are achieved by combining: –Hyperfractionation, –Reduction of the overall treatment time, –Brachytherapy whenever applicable –Better treatment planning (conformal, IMRT)

80 Missed opportunities Rectal cancers…..

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 Surgery vs. pre-operative RT pts. T2 T3 T4 Nx M0 34,5 Gy/15 fr/18 d, L3, AP/PA. Surgery alone 30% vs. Pre-op 15% p=0.003 Conservative surgery: 77 % vs. 86 % Survival benefit in favour of Pre-op in pts with curative resection (69% vs. 59%). Gérard A et al: Ann Surg 208: , 1984 Surgery alone 30% vs. Pre-op 15% p= yr local relapse:

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 survival with pre-operative radiotherapy in resectable rectal cancer * The New England Journal of Medicine: (1997; 336:980-7.) April 3, * Dr Lars Pâhlman & al.

85 from March 1987 to Feb 1990 Patients' selection: Resectable rectal adenocarcinoma (including T1). Age < 80 non metastatic Study design: Surgery alone versus pre-operative Radiotherapy (surgery 1week later) The Swedish rectal cancer trial

86 Radiotherapy scheme: 25 Gy in 5 fractions and 5 days 4 fields box-technique PTV: pelvis to L5 included. Accrual: 1168 patients accrued from the six regional oncological centres of Sweden (in fact 70 hospitals) The Swedish rectal cancer trial

87 At 5 years: The Swedish rectal cancer trial Results Local relapse rate: 27% Surgery alone vs. 11% Pre-operative RT p<0.001

88 Overall 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) The Swedish rectal cancer trial Results

89 Local recurrence rate per stage and treatment Surgery 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 % The Swedish rectal cancer trial Results

90 Preoperative radiotherapy of resectable rectal cancers improves significantly: –Loco regional control (of at least 50%) –Overall survival –Disease free survival (of about 20%) Preoperative radiotherapy is now the standard approach for clinically staged resectable T2 T3 T4 The Swedish rectal cancer trial Conclusions

91 TME ± Pre-op XRT % Local Failures, Follow-up > 2 years XRT + TME TME alone Upsalla Stockholm (3/213) (18/168) Sweden + Norway Confirmed in 2001 by the Dutch randomised trial.

92 RT in rectal cancers Hopefully 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 : a 4-arm multi-factorial design. Pre-op XRT 45 Gy in 5 wks + 5FU-LV + 5FU-LV SURGERY No further Trt Post-op Post-op + 5FU-LV + 5FU-LV Cooperative Group of Radiotherapy:J.F. BOSSET Study coordinator

95 EORTC TRIAL Inclusion Criteria Rectal adeno Ca T3 T4 Nx M0 UICC 87 TR Ultrasound Clin. resectable WHO 0-1 Age < 75 Stratification: Institution Sex Tumor location Stage Exclusion: Unfit for post-op. Trt Metastases Unresectable or incomplete surgery

96 EORTC TRIAL Status as of April 8, Entered: 932 Required: 992 Projected 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)

98 A few guesses for the near future…

99 A few guesses for the near future (1) High precision radiotherapy Resulted 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) Adopted by the Academys Committee for Head & Neck Surgery and Oncology Robbins et al, 1991 The present … which CTV for the neck ?

101 Oropharyngeal Carcinoma Which CTV for the neck? StageIpsilateral neckContralateral neck N0-N1II-III-IV + RP for post. II-III-IV + RP for post. pharyngeal wall tumor N2a-N2bI 1 -II-III-IV-V +RP II-III-IV + RP for post. pharyngeal wall tumor N2cAccording to N stage on According to N stage on each side of the neck N3 I-II-III-IV-V +RP ± adjacent II-III-IV + RP for post. structures according to clinical pharyngeal wall tumor judgment 1 Ib only for N2a Courtesy of V. Grégoire (Brussels)

102 CT-based delineation of lymph node levels in the neck: Brussels-Rotterdam consensus guidelines Ant.symphysis menti / platysma Post.hyoid bone / submandibular gland Lat.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 bone Level Ia and Ib RP LII LIb LIa Courtesy of V. Grégoire (Brussels)

103 Ant.submandibular gland post. belly of digastric m. Post.sternocleidomastoid m. Lat.sternocleidomastoid m. Med.paraspinal m. int. carotid artery Cra.lateral process of C1 Cau.hyoid bone Level II LV LII LIb CT-based delineation of lymph node levels in the neck: Brussels-Rotterdam consensus guidelines Courtesy of V. Grégoire (Brussels)

104 Ant.sternohyoid m./ sternocleidomastoid m. Post.sternocleidomastoid m. Lat.sternocleidomastoid m. Med.paraspinal m. int. carotid artery Cra.hyoid bone Cau.cricoid cartilage Level III LV LIII CT-based delineation of lymph node levels in the neck: Brussels-Rotterdam consensus guidelines Courtesy of V. Grégoire (Brussels)

105 Ant.sternocleidomastoid m. Post.sternocleidomastoid m. Lat.sternocleidomastoid m. Med.paraspinal m. int. carotid artery Cra.cricoid cartilage Cau.2 cm cranial to sternoclavicular joint Level IV LIV LVI CT-based delineation of lymph node levels in the neck: Brussels-Rotterdam consensus guidelines Courtesy of V. Grégoire (Brussels)

106 Ant.sternocleidomastoid m. Post.trapezius m. Lat.platysma / skin Med.paraspinal m. Cra.hyoid bone Cau.transverse cervical vessels Level V LV LIII LVI CT-based delineation of lymph node levels in the neck: Brussels-Rotterdam consensus guidelines Courtesy 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.

111 A truly last word… Thank you…


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