The document discusses standards for precision in radiation oncology, including definitions of target volumes and dose reporting levels according to International Commission on Radiation Units and Measurements (ICRU) reports. It notes unresolved issues for 3D conformal radiation therapy and intensity-modulated radiation therapy, such as margins between gross tumor and clinical target volumes. The document recommends that a new ICRU report is needed to address these modern radiotherapy techniques and provide common guidelines.

1. Precision in Radiation Oncology: what are the standards and how could it apply to IORT Vincent GREGOIRE, MD, PhD, hon. FRCP Radiation Oncology Dept., & Center for Molecular Imaging and Experimental Radiotherapy, Université Catholique de Louvain, St-Luc University Hospital, Brussels, Belgium

2. Bataini et al, 1982 , 4 5 5 5 6 5 7 5 8 5 9 5 T o t a l d o s e ( G y ) 0 2 0 4 0 6 0 8 0 1 0 0 1 2 0 Tumor control (%) Dose-response curve for neck nodes ≤ 3 cm Tumor Control Probability (TCP)

3.  Human  Monkey Baumann et al., Strahlenther Onkol 170: 131-139, 1994 Normal Tissue Control Probability (NTCP)

4. Target J. John, 1974

5. ICRU report 62, 1999 Gross Tumor Volume: GTV Clinical Target Volume: CTV Internal Target Volume: ITV Planning Target Volume: PTV Organ at Risk: OAR Planning Organ at Risk Volume: PRV Target volumes in Radiation Oncology: ICRU 50 and 62:

6. Target volumes in EBRT Before Rx-CH 46 Gy (Rx-CH) Right piriform sinus (ICDO-10: C12.9) SCC grade 2 TNM 6 th ed: T4N0M0 Fiberoptic examination CT MRI T2 FS FDG-PET

7. The Clinical Target Volume (CTV) is a volume of tissue that contains a demonstrable GTV and/or subclinical malignant disease at a certain probability considered relevant for therapy…, The CTV is thus an anatomical-clinical concept. Clinical Target Volume (CTV) ICRU IMRT report Target volumes in EBRT

8. Clinical Target Volume (CTV) Target volumes in EBRT

9. Mesorectal subsite Lymph node regions Posterior PS Selection and delineation of Target Volume Haustermans et al., 2005

10. The Planning Target Volume is a geometrical concept, introduced for treatment planning and evaluation. It is the recommended tool to shape dose distributions that ensure with a clinically acceptable probability that an adequate dose will actually be delivered to all parts of the CTV… Planning Target Volume (PTV) ICRU IMRT report Target volumes in EBRT

11. CTV 2 = GTV 2 ICRU IMRT report Target volumes in EBRT PTV 1 : dose 1 CTV 1 GTV 1 (pre-RxTh CT+ iv contrast) PTV 2 : dose 2 GTV 2 (FDG-PET @ 46 Gy)

12. Target volumes in IORT + EBRT CTV 1 = “tumor bed” PTV 1 = PTV 1 : dose 1 IORT PTV 2 : dose 2 CTV 2 (clinical knowledge) EBRT

13. Normal tissues in EBRT Distinction between “serial-like” (e.g. spinal cord) and “parallel-like organs” (e.g. parotid gland), For “tubed” organs (e.g. rectum) wall delineation, Remaining Volume at Risk (RVR): optimization and late effects (e.g. carcinogenesis). Organ At Risk (OAR) and Remaining Volume at Risk (RVR) ICRU IMRT report

14. PRV is a geometrical concept (tool) introduced to ensure that adequate sparing of OAR will actually be achieved with a reasonable probability , A positive OAR to PRV margin for serial organ. Dose-volume constraints on OAR are with respect to the PRV, Priority rules when overlapping PTVs or PTV-PRV(OAR), Dose is reported to the PRV. Planning Organ at Risk Volume (PRV) ICRU IMRT report Normal tissues in EBRT

15. IORT and Target Volumes GTV is typically absent Clinical definition of the CTV: “the operative bed”… PTV = CTV OAR = PRV are less clearly individualized ICRU report 71, 2004

16. The Human Condition. R. Magritte, 1935

17. Absorbed dose in EBRT Planning aims: PTV 1 : dose x , D-V constraints, …, Spinal cord: D max = x Gy, …, … Prescription: Physician’s responsibility, Acceptance of doses, fraction #, OTT, D-V constraints, beam number, beam orientation, … Treatment delivery: Instruction file sent to the linac and/or RVS. Dose prescription in 3D-CRT and IMRT ICRU IMRT report

18. Level 1: not adequate for 3D-CRT – IMRT, Level 2: standard level for dose reporting, Level 3: homogeneity, conformity and biological metrics (TCP, NTCP, EUD, …) and confidence intervals. Dose recording in 3D-CRT and IMRT Level of reporting Absorbed dose in EBRT ICRU IMRT report

19. ICRU Reference Point Not A “Typical Point” for IMRT Segments 4-7, 9-13 13 segment IM Field From Jatinder Palta, University of Florida Absorbed dose in EBRT Segment 1 Segment 2 Segment 3 Segment 8

20. Dose-volume reporting: D v : i.e. D 50 (D median ), D 95 D mean Near minimum dose: D 98 Near maximum dose: D 2 State the make, model and version number of the treatment planning and delivery software used to produce the plans and deliver the treatment. Metrics for level 2 reporting of PTV Absorbed dose in EBRT ICRU IMRT report

21. “ Serial-like” organs: D near-max (D 98 ). “ Parallel-like” organs: D mean (e.g. parotid) , V d where d refers to dose in Gy (e.g. V 20 for lung). Metrics for level 2 reporting of PRV Absorbed dose in EBRT ICRU IMRT report

22. Homogeneity and Conformity Low Homogenenity – High Conformity High Homogeneity – Low Conformity Dose Dose Dose Dose Vol Vol Vol Vol Absorbed dose in EBRT ICRU IMRT report Vol Dose Vol Dose Vol Dose Vol Dose High Homogeneity – High Conformity Low Homogeneity – Low Conformity

23. IORT and dose prescription, reporting and recording Level 1 (2-D) dose prescription, reporting and recording… Dose prescription at 90% isodose for electron beams Reporting of ICRU reference point dose, and best estimate of D min and D max Recording as for EBRT ICRU report 71, 2004

24. Recommendations for common understanding and proper prescription and reporting especially in combined treatment, e.g. IORT followed by EBRT Less sophisticated prescription and reporting for IORT Volumetric prescription and reporting…? Conclusions

25. Conclusions ICRU recommendations still needed even for 3D-CRT and IMRT to avoid unwanted treatment heterogeneity, New report based on ICRU foundations, e.g. volumes, Adjustments and modifications performed when necessary, e.g. dose-volume reporting, Final draft ready for early 2007 / publication in early 2008 ICRU report on 3D-CRT and IMRT

26. Recording in 3D-CRT and IMRT Electronic archiving for at least the life of patient or 5 years – whatever is longer, Complete reconstruction of the treatment plan and delivery record, For clinical trials, longer archiving if scientifically justified. Absorbed dose in EBRT ICRU IMRT report

27. Sometimes the largest component of the margin between the GTV and CTV will be the delineation error in drawing the GTV, Consideration should be made for this in the clinical margin. Clinical Target Volume (CTV) Target volumes in Radiation Oncology

28. Planning Target Volume (PTV) Target volumes in Radiation Oncology Include both “internal” and “external” variations of the CTV, Separate delineation of the ITV may not be necessary, Expansion of the CTV using “rolling ball” algorithms, CTV to PTV margin recipe based on random and systematic errors, Priority rules when overlapping PTVs or PTV-PRV, Dose is prescribed and reported on the PTV.

29. CTV to PTV margin recipe Target volumes in Radiation Oncology Van Herk, 2003

30. Effect Dose Uncomplicated tumor control: Therapeutic Ratio Unacceptable normal tissue damage Tumour control Uncomplicated tumour control

31. ICRU committee on volume and dose specification for prescribing, reporting and recording special techniques in external photon beam therapy: conformal and IMRT. Vincent GREGOIRE, M.D., Ph.D. and Thomas R. MACKIE, Ph.D.* Radiation Oncology Dept., & Center for Molecular Imaging and Experimental Radiotherapy, Université Catholique de Louvain, St-Luc University Hospital, Brussels, Belgium and * Dept. of Medical Physics, University of Wisconsin, Madison, WI, USA.

32. The stone of Rosette (Champolion)

33. The need for an new ICRU report on 3D-CRT and IMRT Biological Target Volume (BTV): C. Ling, IJROBP 2000, Hypoxic TV (HTV), Proliferation TV (PTV), …: ESTRO physics meeting, 2003, working PTV (wPTV): Ciernik IF, IJROBP, 2005, AAPM 2005: “… with the use of IMRT, ICRU recommendations will not be needed anymore…”. It was published and/or mentioned …

34. ICRU committee for 3D-CRT and IMRT Sponsors Andr é Wambersie MD, PhD, Brussels, Belgium Paul DeLuca PhD, Madison, USA Reinhard Gahbauer MD, Ph.D, Columbus, USA Gordon Whitmore Ph.D, Toronto, Canada Chairmen Vincent Grégoire MD PhD, Brussels, Belgium T. Rock Mackie PhD, Madison, USA Members Wilfried De Neve MD PhD, Gent, Belgium Mary Gospodarowicz MD, Toronto, Canada Andrzej Niemierko PhD, Boston, USA James A. Purdy PhD, Sacramento, USA Marcel van Herk PhD, Amsterdam, The Netherlands Consultants Anders Ahnesjö PhD, Uppsala, Sweden Michael Goiten PhD, Windisch, Switzerland Nilendu Gupta PhD, Colombus, USA

35. ICRU report 62, 1999 Target volumes in Radiation Oncology Unresolved issues for 3D-CRT and IMRT Multiple GTV, e.g. anatomic vs functional imaging; before and during treatment, …, GTV to CTV margins: clinical probability, CTV to PTV margins: geometric probability; overlapping volumes, ITV ??? OAR: open vs closed volume? Remaining normal tissues? PRV: serial vs parallel OAR.

36. Organ At Risk (OAR) PTV Rectal wall Rectum ICRU IMRT report Normal tissues in EBRT

37. Parotid sparing with IMRT ICRU IMRT report Normal tissues in EBRT Superficial lobe Superficial and deep lobe

38. “ Cheating on the PTV margins” The practice of shrinking the CTV to PTV margin to accommodate an OAR is discouraged as it results in a deceptively better PTV homogeneity, In IMRT the trade-off can be accomplished by changing the planning aims in the optimizer, In 3-D CRT, the trade-off can be accomplished with a separate target delineation used to draw the beam boundary. ICRU IMRT report Target volumes in EBRT

39. ICRU report 62, 1999 Absorbed dose in Radiation Oncology: ICRU 50 and 62: Dose prescription: Responsibility of the treating physician. Dose reporting: ICRU reference point, Three-levels of dose reporting, Point-doses: D ICRU point , D min , D max , … Dose recording.

40. ICRU report 62, 1999 Absorbed dose in Radiation Oncology: Unresolved issues for 3D-CRT and IMRT Discrepancy between dose-volume constraint prescription and dose delivery, Single point dose prescription, Single point dose reporting, Biological metrics (e.g. EUD, TCP, NTCP, …), Uncertainties in dose reporting, Quality assurance.

41. Dose-Volume Reporting D 95 D 2 0 10 20 30 40 50 60 70 80 90 100 50 55 60 65 70 Dose (Gy) Percent Volume D98=60Gy D50=60Gy D v with v≠50 may require a change in prescription value D 98 D 50 is close to ICRU Reference Dose at a Point Absorbed dose in EBRT

42. Homogeneity: - Standard deviation in dose to the PTV. Conformity: - Conformity Index: CI = TV/PTV, Dice Similarity Coefficient (DSC): DSC = TV  PTV / TV  PTV  Examples of metrics for level 3 reporting of PTV Absorbed dose in EBRT

43. QA in 3D-CRT and IMRT Appropriate QA of TPS and equipments, Patient QA not limited to single-point dose check, Phantom QA using measured dose and not limited to a single measurement point. Independent dose calculation algorithms with similar or better dose calculation accuracy. Absorbed dose in EBRT

44. QA in 3D-CRT and IMRT Previous ICRU 5% point-dose accuracy specification replaced by a volumetric dose accuracy specification. Proposed new ICRU volumetric dose accuracy specification: High gradient (≥ 20%/cm): 85% of points within 5mm, Low gradient (< 20%/cm): 85% of points within 5% of predicted dose normalized to the prescribed dose. Absorbed dose in EBRT

45. ICRU committee for 3D-CRT and IMRT ICRU IMRT report GTV 1 CTV 1 PTV 1 CTV 2 PTV 2 CTV 3 PTV 3 Microscopic Extension Regional Involvement

46. Example 1 ICRU IMRT report Target volumes in EBRT PTV 1 : dose 1 CTV 1 PTV 2 : dose 2 GTV 1 (pre-RxTh CT+ iv contrast) CTV 2 = GTV 1

47. Dose-Volume Reporting D 50 best corresponds to the level at D ICRU-point Absorbed dose in EBRT 0 10 20 30 40 50 60 70 80 90 100 0 5 10 15 20 25 30 35 40 45 50 55 60 65 Dose (Gy) Percent Volume Differential Cumulative D 95 D 98 D 50 D 2 D 50 = 60 Gy