1. Conformal Therapy for Lung Cancer B. Schicker, F.J. Schwab*, U. Götz Institute of Radiotherapy and Radiation Oncology St. Vincenz-Krankenhaus Limburg *Clinic of Radiotherapy University of Würzburg B. Schicker, F.J. Schwab*, U. Götz Institute of Radiotherapy and Radiation Oncology St. Vincenz-Krankenhaus Limburg *Clinic of Radiotherapy University of Würzburg

2. Definition INTRODUCTION For lung cancer radiotherapy is an essential treatment mode. The major problem for the treatment planning is the fact that the target volume is surrounded by organs at risk. Acute or late reactions of the lung, the myelon and the heart are dose limiting factors. If curative doses are aspired the old fashioned opposed fields techniques are not applicable because of the high dose load to the organs at risk. Curative doses for lung cancer, however, usually exceed 70 Gy. Therefore conformal treatment techniques have to be developed aiming at the reduction of the normal tissue complication probability and the high tumor control probability.

3. ADJUVANT TREATMENT For local advanced tumor stages the postoperative irradiation of the regional lymphatics and of the bronchial stump is indicated. The mediastinum should always be included in the clinical target volume if involved nodes were found but no systematic lymph node dissection was performed. The supraclavicular lymph nodes are not included in the CTV for adjuvant treatment with curative intent. The involvement of these lymph nodes probably improves local control, whereas the improvement of survival remains questionable. The lymph nodes included in the CTV are: the intrapulmonary, the subcarinal, the tracheobronchial, the paratracheal and the preaortic group. For lower lobe primaries the inclusion of the lymph nodes along the ligamentum pulmonale and the paraesophageal nodes should be considered.

4. Radiotherapy decades ago

5. Conventional Opposed Fields Technique based on radiographs

6. Conventional Opposed Fields Technique Change from Radiograph to Target Volume Traditional irradiation portals recommended in textbooks for irradiation of lung cancer patients. selected clinical target volume based on the oncological prin- ciples (no inclusion of the supraclavicular and contra- lateral hilar lymph nodes in the CTV for curative RT).

7. Development of Conformal Treatment Techniques u first step: precise definiton of the planning target volume based on oncological criteria u conformal treatment = precise irradiation of a precisely defined PTV u first step: precise definiton of the planning target volume based on oncological criteria u conformal treatment = precise irradiation of a precisely defined PTV

8. Target Volume for adjuvant treatment Z +8 Z +3 Z +0 Z -2 Z -4 Z -8

9. Definition CONFORMAL RADIOTHRAPY A high dose to the PTV means a high tumour control probability were as a low dose to the normal tissue or organ at risk means a low normal tissue complication probability Low side effects = live quality for the Patient BENEFIT FOR PATIENT

10. Ideal Treatment vs. Reality Ideal: D(PTV) = 100% D(NT,OAR) = 0% Real: D(PTV) ~ 100% D(NT,OAR) >> 0% Dose Distribution

11. Dose Volume Histogram Dose [%] Volume [%] 100 PTV Dose [%] Volume [%] 100 Normal Tissue, Organ at Risk Ideal Treatment vs. Reality

12. u High TCP and low NTCP: high dose within the PTV and a good protection of the OAR u Reduction of the dose to the OAR below critical values (tolerance doses) u Concentration of the therapeutic dose on the PTV: Dose homogeneity within the PTV (ICRU recommendations -5 %... +7 %) u High TCP and low NTCP: high dose within the PTV and a good protection of the OAR u Reduction of the dose to the OAR below critical values (tolerance doses) u Concentration of the therapeutic dose on the PTV: Dose homogeneity within the PTV (ICRU recommendations -5 %... +7 %) Aim of the Optimization - minimum requirements -

13. Development of a 3-D Conformal Standard Technique for Lung Cancer u From opposed fields to conformal technique => => ??? ??? u From opposed fields to conformal technique => => ??? ???

14. Definition 3 Dimensional Conformal - CT based Treatment planning - Slice distance 1.0 or 0.5 cm - Definition and delineation of PTV and Organ at risk in every slice - using other imaging procedures as MR, PET etc. -Calculation and optimisation of the dose distribution in every CT slice to achieve a homogenous dose distribution

15. PTV Lung Heart Myelon Development of a Standard Technique for Lung Cancer

16. PTV Lung Heart Myelon Development of a Standard Technique for Lung Cancer

17. PTV Lung Heart Myelon Development of a Standard Technique for Lung Cancer

18. PTV Lung Heart Myelon Development of a Standard Technique for Lung Cancer

19. PTV Lung Heart Myelon Development of a Standard Technique for Lung Cancer

20. PTV Lung Heart Myelon Development of a Standard Technique for Lung Cancer

21. PTV Lung Heart Myelon Development of a Standard Technique for Lung Cancer

22. Development of a Standard Technique Standard Beam Set up - Isocenter – placed at the ventral tip of the vertebral body - easy to find uneder X-Ray controll from 0° and also 90° gantry angle

23. Development of a Standard Technique Standard Beam Set up Aim of Field 1 is to spare a maximum volume of both lungs

24. F1 0°

25. Development of a Standard Technique Standard Beam Set up The gantry angle and blocking of field 2 (135°) was chosen to protect the myelon

26. F2 135°

27. Development of a Standard Technique Standard Beam Set up Field 3 (40°) reduce the high dose regions in the left lung and contribute to a better adaptation of the isodoses to the PTV

28. u 3 fields: 0° fixed wedge (lung) ~ 140° fixed wedge (myelon) 40°... 80° fixed or arc, wedge ? (heart, contralateral lung, myelon) start with dose contribution 1 : 1 : 1 u field shaping using beams eye view u good protection of the contra-lateral lung u myelon dose (adjustable from 30% to 70%) below critical values for curative total doses u 3 fields: 0° fixed wedge (lung) ~ 140° fixed wedge (myelon) 40°... 80° fixed or arc, wedge ? (heart, contralateral lung, myelon) start with dose contribution 1 : 1 : 1 u field shaping using beams eye view u good protection of the contra-lateral lung u myelon dose (adjustable from 30% to 70%) below critical values for curative total doses Standard Technique at the ISRO Limburg

29. Clinical Case 1 Adjuvant Treatment The 72 year old patient with a non small cell left localized lung cancer was operated. The primary lung cancer infiltrated the left pulmonary artery. A questionable R0 resection was performed. An adjuvant radiotherapy was indicated. From 12 examined lymph nodes 5 were found involved. A total dose of 66.6 Gy was applied in this clinical case. For the main series the target volume was treated with a dose of 50.4 Gy and for the boost technique a dose of 16.2 Gy was given. For both series a dose per fraction of 1.8 Gy was chosen.

30. ZV +4 cm

31. ZV -1 cm

32. ZV -3 cm

33. Clinical Case 1

34. Field 3 (35°) and 4 (100°) reduce the high dose regions in the left lung and contribute a better adaption of the isodoses to the PTV.

35. Clinical Case 1 Full homogeneity over all slices requires two further fields (5 and 6).

36. Technique for Case 1 Variation of the Standard Technique Conformal Therapy for Lung Cancer First International Symposium on Target Volume Definition F.Schwab

37. HS +6 cm95%85%70%50%95%85%70%50% Clinical Case 1

38. HS +4 cm95%85%70%50%95%85%70%50% Clinical Case 1

39. HS 0 cm95%85%70%50%95%85%70%50% Clinical Case 1

40. HS -1 cm95%85%70%50% Clinical Case 1

41. HS -3 cm95%85%70%50%95%85%70%50% Clinical Case 1

42. HS - 4 cm95%85%70%50%95%85%70%50% Clinical Case 1

43. Clinical Case 1 frontal / sagittal dose distribution 100% 95% 90% 85% 80% 70% 50% 30% 10% frontal sagittal

44. Clinical Case 1 DVH PTV Lung Myelon

45. Clinical Case 1 DVH Box / 3 Field Technique PTV Lung Myelon

46. Clinical Case 1 Boost

47. Clinical Case 1 Boost – Beam Setup

48. BST -1 cm 95%85%70%50%95%85%70%50%

49. Clinical Case 2 Radiotherapy after Pneumonectomy A 46 year old male patient with a left located non small cell lung cancer of the upper lobe with infiltration of the upper lung vein. Nine involved nodes from 29 examined nodes were described. In many of the examined lymph nodes a capsule disruption was found. The CTV includes the paratracheal area, the upper mediastinum, the aortic pulmonary window, the left hilus and the subcarinal area. The lymph node capsule disruption and the infiltration of the upper pulmonary vein determine the necessity of a high total dose (at least 66 Gy).

50. Clinical Case 2

51. 100% 95% 90% 85% 80% 70% 50% 30% 10% + 8 cm Clinical Case 2

52. 100% 95% 90% 85% 80% 70% 50% 30% 10% +6 cm Clinical Case 2

53. 100% 95% 90% 85% 80% 70% 50% 30% 10% - 2 cm Clinical Case 2

54. PTV Myelon Lung 100% 95% 90% 85% 80% 70% 50% 30% 10%

55. Clinical Case 3 Definitive radiotherapy A primary inoperable periphery non-small cell lung cancer of the right upper lobe was diagnosed for the 77 year old female patient. In this case the CTV included only the tumor with small margins as shown in figure 23A and B. A total dose of 68.4 Gy was applied.

56. Clinical Case 3

57. 95%85%70%50%95%85%70%50%

58. 95%85%70%50%95%85%70%50%

59. u do the isodoses only look nice or can the patient profit from the conformal technique? u => analysis of the DVHs u Treatment Index TI TI := QI(PTV)/(Dmax(m)*QI(m)+Dmean(l)*QI(l)+Dmean(h)*QI(h)) TI := QI(PTV)/(Dmax(m)*QI(m)+Dmean(l)*QI(l)+Dmean(h)*QI(h)) m = myelon l = lung (left and right) l = lung (left and right) h = heart / myocard side condition: no violation of critical doses u do the isodoses only look nice or can the patient profit from the conformal technique? u => analysis of the DVHs u Treatment Index TI TI := QI(PTV)/(Dmax(m)*QI(m)+Dmean(l)*QI(l)+Dmean(h)*QI(h)) TI := QI(PTV)/(Dmax(m)*QI(m)+Dmean(l)*QI(l)+Dmean(h)*QI(h)) m = myelon l = lung (left and right) l = lung (left and right) h = heart / myocard side condition: no violation of critical doses Evaluation of the Treatment Plans

60. TI=QI(PTV)/(Dmax(m)*QI(m)+Dmean(l)*QI(l)+Dmean(h)*QI(h))TI=QI(PTV)/(Dmax(m)*QI(m)+Dmean(l)*QI(l)+Dmean(h)*QI(h)) Evaluation of the Treatment Plans Treatment Index

61. The prerequisite for a conformal therapy is a precisely defined target volume in a 3D patient model. The target volume has to be defined on the basis of oncological criteria and the success of the therapy has to be checked in clinical studies. The clinical target volumes presented here for the adjuvant and definitive radiotherapy are different from that nowadays usually shown in the clinical textbooks. Conclusions and Discussion

62. One of the advantages of conformal treatment planning is the reduction of the dose load to the normal tissue and to the organs at risk compared to an opposite field technique. The dose at the organs at risk is lowered in two ways: First the total dose is reduced on the basis of the conformal treatment and second the dose per fraction is reduced resulting in a lowering of the biological effective dose at the organs at risk. Both effects in combination allow the application of curative doses to the target volume. The conformal techniques, however, also require an improvement in patient positioning. Finally, modern techniques like intensity modulated therapy may in future help to improve the homogeneity of the dose distribution. Conclusions and Discussion

63. u conformal therapy => improvement of the treatment quality u conformal therapy => reduction of the high dose region for the OARs (responsible for side-effects) u lowering of the daily dose to the OAR additionally reduces the biological effective dose u IMRT for enhanced dose homogeneity u optimized depth doses (proton facilities) u conformal therapy => improvement of the treatment quality u conformal therapy => reduction of the high dose region for the OARs (responsible for side-effects) u lowering of the daily dose to the OAR additionally reduces the biological effective dose u IMRT for enhanced dose homogeneity u optimized depth doses (proton facilities) Conclusion and Future