1. Challenges in Optimal Delivery of Radiation in Head and Neck Cancers Dr. J P Agarwal Associate Professor Department of Radiation Oncology Tata Memorial Hospital, India TMH ESTRO EBM 2005

2. Accounts for about 4,50,000 cases worldwide* 20% of cancer burden - 1,50,000 new cases in 2000 in India* TMH - 25% of all new cases annually > 75 % present with advanced disease Head and Neck Squamous Cell Carcinoma *Globocan,2002 IARC

3. General Management Guidelines for H & N Cancers Aim Highest loco- regional control Anatomical with functional preservation Stage I / II Single modality ( Surgery or RT ) Stage III / IV Combined modality Surgery + RT (in most patients) Chemotherapy + RT in selected patients When different modalities available, one with maximum chance of cure should be used When different modalities have same results, one offering better quality of life, with organ, function preservation and good cosmetic results should be used

4. Head And Neck Radiotherapy A Challenge for The Radiation Oncologist Tumor Very Close proximity Of Tumor and Critical structures Total Dose Delivery Limited by Tolerance of Normal structures Dosimetric Challenges Due to Varying Contour/Tissue Heterogeneity Patient Compromised Tolerance To Treatment Poor Nutritional Status and Weight Loss Inadequate oral Intake Treatment Induced Mucositis

5. The Goal Optimal Dose Delivery …With Minimum Acute And Long Term Toxicity

6. Evolution Of Head And Neck Radiotherapy 1970-2005 Escalation Of Doses Through Precise Immobilization Tissue Compensation/Customized Blocks Better Skin Sparing (Megavoltage) Integration of brachytherapy 3DCRT /SRT/ IMRT

7. Key Issues In Head And Neck Radiotherapy Set up Uncertainties Target Volume Delineation Precise Treatment Planning & Delivery Locoregional control & Overall Survival Overall Treatment Time Nutritional support & Quality of Life

8. The changing paradigm Wide field radiation Conformal radiation Clinical motivation for high-precision techniques More conformality = Better sparing

9. Key Issues In Head And Neck Radiotherapy Set up Uncertainties Target Volume Delineation Precise Treatment Planning & Delivery Overall Treatment time Locoregional control Overall Survival. Nutritional status & Quality of life

10. Conformal Radiotherapy ……The Need For Higher Accuracy Immobilization Devices used Head Rest alone POP with Head Rest Mouth Bite, Nasion & Chin support Thermoplastic Moulds Varying levels of level of Uncertainty Set up errors 5 mm-1 cm.

11. Head and Neck Immobilization devices 3 Clamp 4 Clamp5 Clamp Random Errors with different Fixation devices Radiotherapy Oncology,2001

12. Incorporation of EPID. Cone beam CT Correction Software IGRT Verification Of Patient Positioning

13. Radiotherapy And Oncology 2001. Systemic & Random Errors

14. Immobilization and Set Up Uncertainties Needs with the changing Paradigm Permissible Errors with State of Art equipment: Recommendations for Good Clinical Practice

15. Guidelines for patient positioning in head and neck cancer Setup the patient with neutral neck position. minimizes intra-fraction patient motion Use a customized head and neck support and face mask for each patient. improves accuracy of field matching (Neck and LAN fields) Index immobilization apparatus to the treatment table. Improves treatment setup efficiency and accuracy Use active patient position monitoring system (LED camera System) Improves setup accuracy and reproducibility, and minimizes intra- fraction patient motion These strategies can reduce the setup random errors to less than 2 mm for upper neck.

16. Tackling The Time…The Fourth Dimension Asselen et al IJROBP:56:2004 Range:7mm

17. Key Issues In Head And Neck Radiotherapy Set up Uncertainties Target Volume Delineation Precise Treatment Planning & Delivery Locoregional control & Overall Survival Overall Treatment Time Nutritional support & Quality of Life

18. Challenges In Planning Radiation Treatment Shoot The Tumor….Save The Man

19. Guidelines For Target Volume Delineation 7 Different Groups……Variations in the Target Volume Delineation Novak et al, Vijjers et al, Som et al, Gregoire et al, Palazzi et al, Van Triest et al, Gregoire et al Implications on Target Volume Delineation

20. Heterogeneity In Target Volume Delineation Sanguinetti et al IJROBP,2004

22. Imaging for target volume delineation Does Fusion Help ?

23. Variations In Target Coverage with CT/ MRI Where Do we Stand?.....Where Do we Go? Emami et al IJROBP,2003

24. Variations In Target Coverage with CT/ MRI fusion In Nasopharyngeal Primary MRI & CT are complementary

25. Is PET-CT the way ahead ?

26. Heron et al IJROBP,2004

27. PET CT Fusion And Effect On PTV Reduction In size of PTV at Primary Primary GTV CT/GTV PET = 3 Node Node PET/Node CT= 0.7 Heron et al IJROBP,2004

28. Integration Of Biological Imaging In Target Volume Delineation Ling et al IJROBP:47:2001

29. Key Issues In Head And Neck Radiotherapy Set up Uncertainties Target Volume Delineation Precise Treatment Planning & Delivery Locoregional control & Overall Survival Overall Treatment Time Nutritional support & Quality of Life

30. Variation of Neck Contour at Different Levels causes Under and Overdosage….

31. Close Proximity of Target Volume & Critical structures

32. Heterogeneities within the H & N pose difficulty in treatment planning delivery Air Sinuses Bone Varying Contour & Tissue Heterogeneities Soft Tissue

33. Is Planning At the Initiation of Treatment Enough?

34. ASTRO,2004 Evaluation on 13 patients Mean time to rescanning 37 days Results of Replanning Reduction of dose to CTV &PTV (upto 8 Gy underdosage. Over dosage to the Spinal Cord (Spinal Cord D Max exceeded 45 Gy in 92% patients). Recommendations Should be undertaken in patients having significant weight loss during chemoradiotherapy.

35. Key Issues In Head And Neck Radiotherapy Set up Uncertainties Target Volume Delineation Precise Treatment Planning & Delivery Locoregional control & Overall Survival Overall Treatment Time Nutritional support & Quality of Life

36. Dose escalation Altered Fractionation Schemes Chemoradiotherapy Biological Therapy And Molecular Targetting Improving Efficacy of Irradiation

37. Higher doses up to 70 Gy are related with better locoregional control,however with enhanced acute and long term complications Tata Memorial Hospital Dinshaw et al (in press)

38. Altering The Physical Dose Tissue Compensators Wedges Integration of Brachytherapy/3DCRT/SRS Boost. Altering The Biological Dose Altered Fractionation Schedules. Chemoradiotherapy Schedules Aids In Escalating Dose

39. Attempts in precise dose delivery with minimal toxicity Conformal RT/ 3DCRT/ IMRT/IMPT Conventional 3-D CRT IMRT IMPT

40. Averaged End Point doses for T1/T2 tumors Averaged End Point doses for T3/T4 tumors IJROBP,2004

41. 15 Randomized Trials of Varied Fractionation (1970-1998) 7073 patients 3% Increase In absolute Survival 7% Increase in locoregional control Maximum Benefit in Hyper fractionated RT with Increased Total Dose

42. ChemoRadiotherapy Absolute benefit of CT – 5% at 5yrs Higher For Platinum Based Regimens. No Benefit of NACT (MACH- NC update) However NACT may still have a role in organ and function preservation as in Laryngeal tumors

43. Can this depiction of enhanced tumor control translated into the clinics?

44. Fractionation IMPACT (Intergroup Merger of Patient Data from Altered Or Conventional Treatment Schedule) EORTC 22791,22811,22851, PMH Trial, CHART

45. Comparison of toxicity profile Conventional Vs Altered Fractionation Trotti et al IJROBP,2000

46. Toxicity Profile with Chemoradiotherapy Trotti et al IJROBP,2000

47. Key Issues In Head And Neck Radiotherapy Set up Uncertainties Target Volume Delineation Precise Treatment Planning & Delivery Locoregional control & Overall Survival Overall Treatment Time Nutritional support & Quality of Life

48. Effect of Interruptions on Local control 0.9 Gy loss Per day of Interruption. 0.7-1.4% decrease in probability of local control for every missed day 14-20% decrease in locoregional control for a gap of 7 days

49. N= 22 PORT within 7 weeks / later LRC 70% (PORT within 7 weeks) 27%(PORT more than 7 weeks) Importance of the Time interval between surgery and postoperative radiation therapy in the combined management of head and neck cancers Bhadrasain V,IJROBP,1979

50. Effect of delay in PORT on survival Bastit et al, IJROBP,2001

51. Key Issues In Head And Neck Radiotherapy Set up Uncertainties Target Volume Delineation Precise Treatment Planning & Delivery Locoregional control & Overall Survival Overall Treatment Time Nutritional support & Quality of Life

52. Effect of Hb Levels on locoregional control in HNSCC Macdonald et al Clin Onco,2004IJROBP,1997 Effect of Anemia on Locoregional control & Survival: Analysis of results fro RTOG 85-07 HemoglobinLRCSurvivalLate RT complications Low =28936 %21%13% High =16263%36%19% P=0.06P=0.0003P=0.054 Hb > 13 Hb < 13

53. The Children of lesser GOD….effect of poverty and low socioeconomic status on outcome Clinical Oncology,2002

54. Socio-demographic variables influence outcome in Radiation Therapy Oncology Group head and neck trials 9111,9003,9703. Income Marital status Baseline nutrition Education Level Independent prognostic value in determining Locoregional Control & Overall survival ASTRO Proceedings 2002,2004

55. Issues in Quality Of life Xerostomia Swallowing Dysfunction, Dysphagia and Aspiration Speech Dysfunction Post Treatment Nutritional Intake Adjustments with Body Image especially in patients with extensive Facial Distortion following Surgery. Depression

56. Is this Data Applicable in Developing World ?

57. Infectious diseases are the main killers Patients present in an advanced stage Fund allocation to Health is less than that of developed Countries No Social Health Security System Geographic Clustering of facilities to urban areas Linear accelerators are expensive, with high operational costs. High precision facilities available in only selected centers.

58. Radiotherapy Oncology,2001Lancet oncology,2004 India Quantitative Resources of Radiation Therapy in Asia Pacific region

59. Radiotherapy units per million population USA 8.3 machines/Million Population

61. How to optimize treatment for developing countries?

62. Optimization of Treatment Good Nutritional Support. Avoidance of Treatment Breaks Integration of Chemotherapy Altered fractionation & abbreviated schedules Integration of high-precision techniques

63. Acceptable local control Acceptable late complication No difference in either groups Early Glottic Ca : Stage I / II Dinshaw et al IJRO BP 48(3) 723-35, 2000 (1975-89) (1975-89) Less protracted schedules can be used

64. Outcomes of response adapted therapy Radiotherapy and oncology,2004

65. 14% 30 Day Mortality Optimal Infrastructure support required for implementation of CTRT/AFRT schedules in developing countries Shaleen K, R & O,2004

66. Lancet Oncology,2004 Three Tier System Primary RT centers EBRT Units Secondary RT centers EBRT/ Brachy Simulators/TPS Tertiary RT Centers Virtual Simulation 3DCRT/IMRT/SRT

67. Take Home Message Set up Uncertainties Restrict systematic and random errors Target Volume Delineation Optimum modality yet to be defined Treatment Planning & Delivery Aim for optimal target coverage Address heterogeneities Locoregional control & Overall Survival. Still A long way to go Overall Treatment time Avoid and correct treatment breaks Nutritional Support & QOL Merits more attention

68. Thank you for your kind attention